NCT05278208Phase 1, Phase 2Recruiting
Nationwide Children's Hospital · Children's Hospital Colorado, Aurora, Colorado
This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4 to \<12 years (Phase I) or 12 to \</=39 years (Phase II) to test its safety and efficacy, respectively.
Funding Source - FDA OOPD (grant number FD-R-0532-01)
Eligibility: 4 Years to 39 Years · All · All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \[68Ga\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.
1. Screening Criteria
1.1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection.
Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
1.2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
1.3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
2. Eligibility Criteria
* Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible.
* Phase II Age Patient must be 12 to \</=39 years at the time of enrollment.
3. Inclusion Criteria
3.1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
3.2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
3.3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
3.4 Investigational/Biologic Agent
●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment.
For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
3.5 Radiation
Patients must have had their last fraction of:
* Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment.
* Focal irradiation \> 4 weeks prior to enrollment
3.6 Stem Cell Transplant
Patient must be:
* ≥ 6 months since allogeneic stem cel
NCT05688683Phase IIRecruiting
Fondation Ophtalmologique Adolphe de Rothschild · Fondation Adolphe de Rothschild, Paris
Interactions between the perceptual and motor systems are fundamental to the performance of complex motor tasks and are at the heart of the fine motor control required for the production of complex sounds such as speech production or playing a musical instrument. In such situations, the brain must learn to generate relevant motor commands to a sound-producing system with fixed physical characteristics, such as the vocal tract or a musical instrument.
No study has yet been able to directly test the dynamic aspect of this sensorimotor learning in an acoustic production task with fine motor control.
The Adolphe de Rothschild Foundation Hospital takes care of patients requiring awake surgery. During these procedures, a direct cortical recording, called electro-corticography, is performed in order to better delineate the tumor or epileptogenic resection area. Reference recordings are made in healthy areas at a distance from the lesion site making it possible to record normal brain activity.
In this case, we would propose to the patient to use a tool similar to the theremin (a musical instrument the size of a golf ball whose displacement in space modulates the frequency and the harmonics of a sound). The patient should therefore learn in order to create relevant motor patterns.
Eligibility: 18 Years to · All · * Benefiting from an intracranial brain recording during a programmed surgery in awake condition.
NCT07359235Phase 1Recruiting
Tongji Hospital · Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
Recombinant oncolytic adenovirus injection (KD01) is an oncolytic virus product. Its main component is a conditionally replicative recombinant human type 5 adenovirus, where part of the E3 region has been replaced with the gene encoding the tBid apoptotic protein.AK104 is a humanized bispecific antibody co-targeting PD-1 (Programmed Cell Death Protein 1) and CTLA-4 (Cytotoxic T-Lymphocyte-Associated Antigen 4)-two key immune checkpoint receptors. It is designed as a novel tetrameric construct that preferentially binds to tumor-infiltrating lymphocytes (TILs) co-expressing PD-1 and CTLA-4 in the tumor microenvironment (with higher avidity than in peripheral tissues).This is a Phase I clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of intravesical instillation of recombinant oncolytic adenovirus injection (KD01) in patients with bladder cancer.This study consists of Phase Ia and Phase Ib, where Phase Ia is a dose-escalation stage.The Phase Ia will include histopathologically confirmed non-muscle-invasive bladder cancer (NMIBC) patients with high-risk stratification (including extremely high-risk).The Phase Ib study will include two independent cohorts: Cohort A comprises high-risk non-muscle-invasive bladder cancer (NMIBC) patients (carcinoma in situ \[CIS\], with or without Ta/T1 stage lesions) who have shown no response to BCG. Cohort B will include T2-4aN0-1M0 stage bladder cancer patients (clinically localized muscle-invasive bladder urothelial carcinoma).
Eligibility: 18 Years to 75 Years · All · * 1.The Phase Ia will include histopathologically confirmed non-muscle-invasive bladder cancer (NMIBC) patients with high-risk stratification (including extremely high-risk). High-risk stratification criteria are defined as G3/high-grade tumors that meet any of the following criteria: carcinoma in situ (CIS); stage T1; diameter\>3 cm; multiple tumors; or recurrent tumors. The Phase Ib Cohort A will include BCG unresponsive NMIBC patients with carcinoma in situ \[CIS\], with or without Ta/T1 stage lesions, while Cohort B will include histopathologically confirmed muscle-invasive bladder cancer (cT2-4aN0-1M0).Note: BCG non-response is defined as meeting any of the following criteria: 1. Persistent or recurrent CIS within 12 months after completing adequate BCG treatment; 2. Recurrence of high-grade Ta/Tl disease within 6 months after completing adequate BCG treatment; 3. High-grade T1 disease at first evaluation after induction BCG treatment. (Adequate BCG treatment is defined as: Complete at least 5 out of 6 doses in the initial induction course. plus 2 out of 6 doses from the second induction course, or 2 doses from the 3-dose maintenance course.)
* 2.Excluding Phase Ib Cohort B, participants must either be medically ineligible for radical cystectomy as determined by urologists or have declined the procedure.
* 3.Age 18 to 75 (including 18 and 75).
* 4.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 1.
* 5.Estimated survival time is ≥2 years.6.No dysfunction of major organs, including but not limited to hematopoietic function and cardiac, pulmonary,hepatic and renal function.
Hematologic system (no history of blood transfusion or hematopoietic growth factor treatment within 14 days)
1. Absolute neutrophil count (ANC)≥1.5×109/L
2. Platelets （PLT）≥75×109/L
3. Hemoglobin （Hb）≥90g/L
Hepatic function
1. Total bilirubin (TBIL)≤1.5× upper limit (ULN)
2. Alanine aminotransferase (ALT)≤3×ULN
3. Aspartate aminotransferase (AST)≤3×ULN
Renal function
1. Creatinine （Cr）≤1.5×ULN
2. Creatinine clearance (Ccr) (Calculation required only if creatinine exceeds 1.5×ULN)\>50 mL/min (calculated using the Cockcroft-Gault formula)
Coagulation function
1. Activated Partial Thromboplastin Time (APTT)≤1.5×ULN
2. International normalized ratio (INR)≤1.5×ULN
* 7.Premenopausal patients must have a negative blood pregnancy test during the screening period;they must agree to use reliable contraceptive methods (barrier contraceptive method or abstinence) with their partners during the trial and for at least 6 months after the last dose.
* 8.Patients must provide informed consent to the trial and voluntarily sign of a written informed consent form before participating in the trial.
NCT05951179Phase 2Recruiting
Protara Therapeutics · Urology Centers of Alabama, Homewood, Alabama
TARA-002-101-Ph2 is an open-label study to investigate the safety and efficacy of intravesical instillation of TARA-002 in adults 18 years of age or older with high-grade CIS NMIBC (± Ta/T1).
The purpose of this Phase 2 study (TARA-002-101-Ph2) is to further assess the safety and efficacy of TARA-002 at the RP2D which has been established in the Phase 1a dose finding study (TARA-002-101-Ph1a).
This Phase 2 study includes participants with CIS NMIBC (± Ta/T1) with active disease, defined as disease present at last tumor evaluation (within 3 months) prior to signing the ICF.
Participants will be enrolled into one of 2 cohorts:
Cohort A:
* Participants with CIS (± Ta/T1) who are BCG naive, or
* Participants with CIS (± Ta/T1) who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis
Cohort B:
* Participants who are BCG unresponsive
Eligibility: 18 Years to · All · * Male or female participants 18 years of age or older at the time of signing informed consent
* Participants who have voluntarily given written informed consent after the nature of the study has been explained according to applicable requirements prior to study entry
* Central histologic confirmation of high-grade non-muscle invasive CIS (± Ta/T1) with active disease
* Participants who are BCG naive, or participants who are BCG exposed and have not received intravesical BCG for at least 24 months prior to the most recent CIS diagnosis (Cohort A). Participants with CIS (± Ta/T1) who are BCG unresponsive.
NCT06929286Phase 3Recruiting
Memorial Sloan Kettering Cancer Center · Johns Hopkins University (Data Collection Only), Baltimore, Maryland
The purpose of this study is to compare the effectiveness of different FDA-approved/NCCN-recommended drug treatments for NMIBC. In particular, the FDA-approved drug nadofaragene firadenovec will be compared to usual care with other NCCN-recommended standard treatments for NMIBC (gemcitabine with or without docetaxel, mitomycin, re-treatment with BCG, or pembrolizumab).
Eligibility: 21 Years to · All · * 21 years of age or older
* Being treated for high-grade NMIBC (Tis, Ta, or T1) under the care of the participating treating urologists
* One or more prior induction course of BCG at any point in time and judgment by the treating urologist that BCG has failed
°Any amount of maintenance BCG is allowed
* In the previous 12 months, receipt of at least one instillation of any intravesical agent (induction or maintenance) or one administration of systemic therapy for NMIBC treatment
* An intravesical agent can include BCG or any other NMIBC treatment
* Up to 15 months from the last instillation is allowed for the treating physician to perform a transurethral resection of bladder tumor (TURBT) so long as there is evidence/suspicion of recurrent disease (by urinary cytology, imaging, or cystoscopy) within 12 months of last exposure to an intravesical agent.
* In the opinion of the treating urologist, there is no contraindication to treatment with nadofaragene firadenovec (i.e. hypersensitivity to IFNa, severe immunosuppression) and there is uncertainty over whether nadofaragene is better than "best usual care"
NCT07322263Phase 2Recruiting
Michael A. O'Donnell · University of Iowa, Iowa City, Iowa
The goal of this clinical trial is to learn whether a combination of two chemotherapy drugs, Gemcitabine and Docetaxel, can treat high-grade non-muscle-invasive bladder cancer (HG-NMIBC) in adults whose cancer failed conventional BCG therapy. The drugs are given directly into the bladder (intravesically), one immediately after the other.
The study will also assess the safety of this treatment.
The main questions it aims to answer are:
Can this drug combination effectively treat HG-NMIBC that did not respond to BCG and help prevent the cancer from coming back, offering long-term protection? What side effects or medical issues do participants experience during treatment?
Researchers will evaluate this non-surgical approach as a potential alternative to bladder removal surgery (radical cystectomy), with the goal of validating it as a bladder-sparing option in this setting.
Participants will:
* Go through a screening process, including tumor removal and imaging tests
* Receive weekly bladder treatments with Gemcitabine followed by Docetaxel for 6 weeks
* If the cancer responds, continue with similar once monthly treatments (maintenance therapy) for up to 2 years
* Attend regular check-ups, including bladder exams, urine tests, biopsies, and optional quality-of-life surveys
* Possibly receive a second 6-week treatment cycle if the cancer returns early
* Be followed for up to 5 years to monitor long-term outcomes
Eligibility: 18 Years to 99 Years · All · Histologically confirmed diagnosis of urothelial carcinoma of the bladder without synchronous or metachronous upper tract involvement or prostatic urethral involvement. Subjects with negative upper tract imaging within 6 months of the study start and visually normal prostates are potentially eligible. Those with a history of suspicious upper tract cytology or suspicious prostatic urethra visually will require additional upper tract washes and/or biopsies to rule out concurrent extravesical disease.
Eligible bladder cancer presentations include:
* Carcinoma in situ (CIS), with or without non-muscle-invasive stage Ta or T1 tumors of any grade.
* High-Grade Papillary tumors (stages Ta and/or T1) without CIS.
* All visible bladder tumors must be completely resected within 8 weeks prior to initiating intravesical Gem/Doce therapy.
* If more than 8 weeks have passed since diagnosis or resection of index bladder CIS ± non-invasive tumor (pTa or T1 tumors), an office cystoscopy must be performed within 8 weeks of Gem/Doce initiation to confirm no visible tumor regrowth.
BCG-Unresponsive Disease as defined by any of the following FDA-accepted criteria:
* Occurrence of high-grade, stage T1 cancer after at least 5/6 weekly BCG induction treatments.
* Occurrence of CIS within 12 months, or high-grade papillary disease, stage Ta/T1, within 6 months after an "adequate" course of BCG therapy.
An "adequate" course of BCG includes at least 5/6 weekly BCG induction treatments and at least 2/3 weekly BCG maintenance or 2/6 weekly BCG re-induction treatments.
* N.B: Physician may have some flexibility (+/- 1 month) in the use of 6 and 12 months to define BCG-unresponsive NMIBC.
* N.B: Once a patient has been correctly defined as having BCG-unresponsive disease, they will be considered to always be BCG-unresponsive for the purpose of this study. In other words, there is no restriction as to when the BCG-unresponsive term was assigned.
* The occurrence of low-grade (LG) Ta disease will not be considered a HG relapse event given its prognosis is much more favorable that HG disease. However, all LG tumor must be completely resected before continuing with Gemcitabine/Docetaxel therapy.
* Subjects must be eligible for radical cystectomy and decline this standard of care treatment or not be a surgical candidate for radical cystectomy (as appropriate) based on other comorbidities.
* All grossly visible disease in the bladder must be fully resected with pathologic stage and grade assessed at the local study institution. Local pathologists are strongly encouraged to use the current LG and HG AJCC criteria.
NB: For institutions that still use the 3-tiered grading system, Ta Gr1 and Gr 2 will be considered LG while any Ta Gr3 or T1 Gr2 or Gr3 will be considered HG.
* Patients enrolled in other clinical trials must have received their last treatment at least 8 weeks prior to enrollment if the treatment was an intravesical agent. If the treatment included a systemic immune-modulating agent (e.g. anti-PD(L)-1 or anti CTLA4) then at least two dosing intervals must have elapsed untreated before the patient is eligible.
* Age \> 18 and must be able to read, understand and sign the local informed consent.
* Patients must have an Eastern Cooperative Oncology Group (ECOG) performance Status of 2 or less, including patients who are not surgical candidates due to comorbid conditions.
* Women of childbearing potential must have a negative pregnancy test at screening.
* All patients of childbearing potential must be willing to consent to using effective contraception, i.e., IUD, Birth control pills, Depo-Provera, and/or condoms while on treatment and for 3 months after their last Gemcitabine/Docetaxel treatment.
* No intravesical or upper tract topical therapy within 8 weeks of study entry.
* Must be willing and able to comply with all protocol requirements.
* Should have a Complete Blood Count (CBC) with differential before the index tumor resection or bi
NCT06488222Phase 2Recruiting
University of Florida · University of Florida, Gainesville, Florida
Bladder cancer is the 8th most common cancer in the UF Health Cancer Center catchment area and the 7th most common cancer presenting to UFHealth. Most newly diagnosed cases are stage I bladder cancer, which is defined by having no deep muscle invasion and no evidence of disease beyond the bladder. The current use in BCG (Bacillus Calmette-Guerin) refractory disease and the ongoing evaluation in BCG naïve high-risk disease support evaluation of intravesical gemcitabine and docetaxel in decreasing disease recurrence in intermediate risk stage I bladder cancer.
This study will investigate the efficacy and subject compliance with treatment of low grade intermediate risk bladder cancer with intravesical gemcitabine and docetaxel.
Eligibility: 18 Years to · All · * Adults ≥ 18 years of age.
* Low-grade (Ta) Intermediate risk urothelial carcinoma of the bladder (defined as recurrent low-grade Ta, solitary low-grade Ta \> 3 cm, multifocal low-grade Ta). Up to 10% high grade component is allowed.
* ECOG Performance Status of 0-2.
* No evidence of upper tract urothelial carcinoma based on CT, MRI, or retrograde pyelograms.
* No urethral involvement based on cystoscopy.
* No visible disease based on cystoscopy within 60 days of study enrollment.
* Neutrophil counts ≥ 1500 cells/mm3
* Platelet counts \>100,000 cells/mm3
* Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen \[as determined by the treating physician or approved by the PI\] may be included.
* Subjects of childbearing potential (SOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for at least 6 months after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, subjects of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
* Subjects with partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 3 months following the last dose of study drug.
* Written informed consent obtained from the subject and the subject agrees to comply with all the study-related procedures.
NCT07339930Phase IIRecruiting
University Hospital, Strasbourg, France · ervice d'Endocrinologie, Diabétologie et Nutrition - CHU de Strasbourg - France, Strasbourg
Polycystic ovary syndrome (PCOS) is the leading endocrine disorder of the reproductive system, affecting 10 to 13% of women of childbearing age. However, there is a significant delay in diagnosis, which may be due to considerable clinical heterogeneity and a lack of information among the general population. The diagnosis is made when two of the three Rotterdam criteria established in 2003 and revised in 2023 are met, namely: 1) menstrual cycle disorders (oligoanovulation) - 2) clinical or biological hyperandrogenism - 3) OPK morphological appearance or elevated anti-Müllerian hormone (AMH) levels, after exclusion of differential diagnoses. PCOS is a condition that carries a risk of metabolic complications and fertility problems due to dysovulation. Patients have an impaired quality of life and are at greater risk of anxiety and depression, which should be screened for systematically.
Eligibility: 18 Years to 49 Years · All · * Adult woman (≥18 years and \<50 years)
* Subject who consulted at the Strasbourg University Hospitals for suspected PCOS or for any other endocrinological condition that led to the discovery of PCOS.
NCT07117045Phase IIRecruiting
Changhai Hospital · Meinian Onehealth Healthcare Holdings Co., Ltd, Shanghai, Shanghai Municipality
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with early diagnosis crucial for improving survival. Due to the absence of effective screening methods, most patients are diagnosed at advanced stages. The population undergoing low-dose computed tomography (LDCT) screening significantly overlaps with those at high risk for PDAC; however, traditional imaging methods have limited sensitivity for detecting pancreatic lesions. This study utilizes the Pancreatic Cancer Detection with Artificial Intelligence (PANDA) system to enhance LDCT for pancreatic cancer screening in a prospective, multicenter, observational cohort. PANDA will analyze LDCT images, followed by a multidisciplinary team (MDT) reassessment of abnormal interpretations. Based on MDT evaluation, individuals will be recalled for further examination, placed under a personalized follow-up plan, or monitored for at least one year. The primary outcomes include pancreatic cancer detection rate, positive predictive value, consensus rate, and recall rate, while secondary outcomes focus on early-stage cancers, resectable tumors, and safety indicators such as false positive rates and unnecessary procedures. This study aims to assess the effectiveness and safety of AI-assisted LDCT for PDAC detection, providing a practical solution for improving public health and enhancing early diagnostic capabilities.
Eligibility: 50 Years to · All · 1. Age 50 years and above.
2. Voluntary signing of informed consent.
3. Completion of LDCT examination.
NCT06277531Phase IIRecruiting
Peking University Third Hospital · Peking University Third Hospital, Beijing, Beijing Municipality
Biliary stricture is mainly malignant in the adults and caused by several types of fatal malignancies such as pancreatic cancer, cholangiocarcinoma, and metastatic tumor, which have poor prognosis that the overall survival of unresectable lesions is no more than 15 months. The poor outcome often relates to a lack of reliable strategies for early diagnosis, which results in most patients with malignant biliary stricture being already advanced-stage disease at presentation. Therefore, it is critical to discover novel and effective strategies for the early diagnosis of malignant biliary strictures.
Brush cytology and biopsy during endoscopic retrograde cholangiopancreatography (ERCP) are the main methods for recognizing malignant diseases of the bile duct, but their sensitivity is relatively low, 45% and 48.1%, respectively. Even when combined with other biomarkers like carbohydrate antigen 19-9 (CA19-9), their sensitivity is still less than 80%.
In the previous study, the investigators found that bcf-eccDNA has excellent diagnostic value in predicting uncertain bile duct stricture, and the sensitivity and specificity of a related eccDNA in 40 samples are 80.8% and 100%. The sensitivity and specificity of another eccDNA were 92.3% and 92.9%, respectively. However, the sample size is still relatively small, and further prospective studies are needed to evaluate its diagnostic efficacy.
Eligibility: 18 Years to 85 Years · All · * Patients is suspected indetermined biliary strictures
* Patients have the indication for ERCP
NCT06801899NARecruiting
Insel Gruppe AG, University Hospital Bern · Department of General, Visceral and Transplantation Surgery, University Hospital Münster, Münster
The goal of this clinical trial is to learn if total removal of the pancreas is a preferable alternative to partial removal in patients with cancer of the pancreatic head who are at high risk of pancreatic leakage. The main question it aims to answer is:
Does total pancreas removal improve survival without reducing quality of life compared to partial removal?
The only study specific procedures are the collection of 2 blood samples (7.5ml for each time point, preoperatively and during the hospitalisation) and the completion of the questionnaires.
Eligibility: 18 Years to · All · * Adult patients (age ≥ 18 years) scheduled to undergo PD for highly suspected or histologically proven, resectable pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (DCC), and/or ampullary cancer (pancreaticobiliary type)
* Suspected pancreas anastomosis at high-risk for development of a postoperative pancreatic fistula (POPF) (grade "D" according to Schuh et al. (29): Estimation by CT scan, MRI, and/or Endoscopic Ultrasound
* Written informed consent
NCT06937177Phase 2Recruiting
Endevica Bio · Arizona Clinical Research Center, Tucson, Arizona
This is a randomized, double-blind, placebo-controlled basket trial evaluating mifomelatide (TCMCB07) administered daily by subcutaneous (SC) injection in up to 120 patients. Patients will be enrolled into two cohorts 1) patients with newly diagnosed, advanced, unresectable colorectal cancer (CRC) or 2) patients with newly diagnosed, advanced, unresectable pancreatic ductal adenocarcinoma (PDAC). Within each cohort, patients will be randomized 1:1:1:1 to receive placebo or one of three different doses of mifomelatide (12.5 mg, 25 mg, or 50 mg). This study is designed to evaluate the effects of different doses of mifomelatide on weight, body composition and BMI. The double-blind (DB) phase will generally begin on the first day of the second cycle of first-line cancer chemotherapy and continue for 12-weeks with the goal of maintaining body weight and muscle mass in patients undergoing chemotherapy relative to control. Upon completion of the DB treatment period, eligible patients may enroll in an optional Open Label Extension (OLE) phase and receive mifomelatide SC 25 mg daily for up to an additional 26 weeks. The purpose of the OLE is to further evaluate long-term safety, tolerability and efficacy of mifomelatide.
Eligibility: 18 Years to · All · Inclusion Criteria:
1. Must be at least 18 years of age.
2. An ECOG performance status of ≤ 2.
3. Life expectancy of ≥ 4 months.
4. Able to eat and digest food normally. Patients with colostomies are allowed.
5. Must meet the following:
1. Newly diagnosed colorectal adenocarcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC) that is unresectable, locally advanced (i.e., surgery with curative intent is not an option) or metastatic. Note: patients must not have relapsed within 6 months after completing prior treatment for early-stage disease.
2. Determined by the Investigator to be ready to receive their second dose of chemotherapy.
3. Patients currently enrolled and receiving study intervention under Protocol Version 2.0 may be eligible to enroll into Protocol Version 3.0, provided the amended protocol has received all regulatory and ethics approvals and the patient has reviewed and signed the updated consent form prior to any procedures conducted under the amended protocol. Enrollment into the OLE phase must occur ≤14 days following completion of the Week 12 DB visit.
6. Patients must be initiating treatment with one of the following chemotherapy regimens:
a) Gemcitabine plus nab-paclitaxel (GNP), Gemcitabine plus capecitabine, NALIRIFOX, FOLFOX, FOLFIRI, or FOLFIRINOX are permitted. These regimens may be administered with or without bevacizumab, other FDA-approved monoclonal antibodies, or other FDA approved agents as clinically indicated for the patient's cancer type. The primary cancer therapy (including dose, schedule, or specific agents) may be modified as medically indicated.
7. Must be able and willing to safely self-inject daily or be injected by a caregiver.
8. Must have evaluable disease by RECIST 1.1.
9. Must have adequate end organ function as defined by:
1. ANC ≥ 1.5 × 10\^9/L
2. Platelets ≥ 100 × 10\^9/L, or adequate as determined by the medical judgement of the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
3. Hemoglobin ≥ 9 g/dL, or adequate as determined by the medical judgement of the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
4. AST and ALT ≤ 3 × ULN; if liver metastases, then ≤ 5 ×ULN; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
5. Bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN in the presence of documented Gilbert's Syndrome; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
6. Albumin between 3.4 and 5.4 gm/dL or within institutional normal limits, or not considered clinically significant by the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
7. Creatinine clearance ≥ 50 mL/min (calculated by Cockcroft and Gault equation; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
8. Normal hemoglobin A1c levels based on institutional normal limits, or not considered clinically significant by the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
10. NT-Pro-BNP and Troponin (TnI or TnT) are within normal limits or not considered to be clinically significant by the investigator; lab may be repeated as needed to rule out initial transient lab abnormality that does not require medical intervention
11. If a female of childbearing capability, must have a negative pregnancy test within 2 weeks of starting treatment.
12. Fertile men and women must agree to use adequate contraception for the duration of the trial.
13. Willing and able to sign informed consent.
14. Additional cohort-specific inclusion criteria:
1. CRC Cohort i. Must have a BM
