NCT05269381Phase 1, Phase 2Recruiting
Mayo Clinic · Mayo Clinic in Florida, Jacksonville, Florida
This phase I/II trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.
Eligibility: 16 Years to · All · Inclusion Criteria COHORT 1 and COHORT 2 are no longer enrolling.
PHASE I PRE-REGISTRATION, ALL:
* Willing to provide tissue specimens per protocol, or have clinically collected formalin-fixed paraffin-embedded (FFPE) tissue blocks, or available sequencing data available from commercial or research tests
* NOTE 1: Includes fresh tissue specimen at pre-registration, or with or clinically collected FFPE tissue blocks for complete exome and transcriptome sequencing. Patients who had tumor sequencing under certain Mayo IRB protocols and neoantigen has been identified or REAL Neo vaccine produced are allowed to proceed to pre-registration and/or registration.
* NOTE 2: This criteria will not apply to patients who had sequencing and neoantigen prediction previously completed.
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* Patients with actionable genomic abnormality including, but not limited to EGFR, ALK, MET, ROS-1, RET, NTRK, KRAS or BRAF must have received and progressed on at least one line of prior FDA-approved targeted therapy
* Provide written informed consent. For pediatric patients (age 16-17 years):
* Written informed consent from legal guardian(s) and/or child obtained in accordance with local regulations.
* Willing to return to enrolling institution for follow-up
* Willing to provide blood specimens for research
* Negative pregnancy test 7 days prior to pre-registration for persons of childbearing potential.
* Willing to employ highly effective method of contraception from pre-registration through 6 months after final vaccine cycle
* Willing to receive tetanus vaccination if subject has not had one ≤ 1 year prior to pre-registration
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
* Anticipated life expectancy \> 6 months
* Recovered from all toxicities associated with prior treatment to acceptable baseline status (see specified inclusion limits for laboratory toxicity) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5 Grade 0 or 1, except for toxicities not considered safety risk per treating investigator (e.g., alopecia or vitiligo).
* The following lab values obtained ≤ 28 days prior to pre-registration:
* Hemoglobin ≥ 9.0 g/dL (Must be ≥ 7 days after most recent transfusion)
* Absolute neutrophil count (ANC) ≥ 1500/mm\^3 or ≥ 1.5 X 10\^9/L
* Platelet count ≥ 100,000/mm\^3 or ≥ 100 X 10\^9/L (Must be ≥7 days after most recent transfusion)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN or ≤ 5 x ULN with liver metastases
* Creatinine ≤ 1.5 x ULN OR calculated creatinine clearance must be ≥ 50 ml/min using Cockcroft-Gault formula
* International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case PT or PTT must be within target range of therapy
PHASE I REGISTRATION, ALL:
* Successful sequencing and production of REAL-Neo vaccine
* Measurable disease as defined by RECIST (v 1.1) criteria or non-measurable disease
* NOTE: Tumor lesions in previously irradiated area are not considered measurable disease
* ECOG PS 0 or 1
* Anticipated life expectancy \> 6 months
* The following lab values obtained ≤ 14 days prior to registration:
* Hemoglobin ≥ 9.0 g/dl
* ANC ≥ 1500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1.5 x ULN
* ALT and AST ≤ 3 x ULN (≤ 5 x ULN with liver involvement)
* PT/INR and aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy in which case INR or aPTT must be within target range of therapy
* Calculated creatinine clearance ≥ 50 ml/min using Cockcroft-Gault formula
* Provide written informed consent
* Willing to provide blood and tissue sp
NCT07621614NARecruiting
Children's Oncology Group · Kaiser Permanente-Oakland, Oakland, California
This clinical trial compares the effect of using risk-based stratification to guide surgical management to the usual approach in treating cutaneous melanoma, atypical Spitz/Spitzoid tumors or other atypical melanocytic tumors that have not spread to other parts of the body (localized). Melanoma is a cancer that in children is sometimes difficult to tell apart from benign (not harmful) or atypical (uncertain if harmful) skin lesions. Failure to diagnose melanoma can result in inadequate surgical removal and increase the risk of recurrence and metastatic disease (spread from where it first started to other places in the body). In addition, diagnosing a tumor a benign (not cancer) tumor as cancer may lead to unnecessary surgery and treatment. This trial reviews tumor pathology and genetic markers and classifies the tumor as not atypical, atypical but low risk for spread and/or recurrence (coming back after a period of improvement), and atypical and high risk for spread and/or recurrence. The classifications are then used to provide surgical recommendations. Tumors that are not atypical do not receive any surgical treatment. Low-risk recommendations include removing a small layer of normal skin around the tumor. High-risk recommendations include the usual adult melanoma approach of removing a larger layer of normal skin around the tumor with or without a biopsy of the sentinel lymph node (the first lymph node to which tumor cells are likely to spread from a primary tumor). Risk-based guided surgical management may help avoid unnecessary surgery while improving outcomes in younger patients with localized cutaneous melanoma, atypical Spitz/Spitzoid tumors or other atypical melanocytic tumors.
Eligibility: to 25 Years · All · * Patients ≤ 25 years old
* Newly diagnosed localized cutaneous melanoma, atypical Spitz/Spitzoid tumors, or other atypical melanocytic neoplasm by local institution pathology report
* Patients must have disease that is localized to the skin on clinical assessment. Note that staging imaging is not required for the determination of eligibility, but if obtained prior to enrollment, all imaging must be consistent with localized cutaneous disease
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* Patients must not have received any prior chemotherapy, immunotherapy, targeted therapy, radiation, or surgical therapy for melanoma other than the permitted biopsy/excision of the lesion for which they are enrolling. Note that prior biopsies/surgery for other benign melanocytic lesions is permitted
NCT03842943Phase 2Recruiting
University of Louisville · University of Louisville, Louisville, Kentucky
Determine safety and efficacy of pre-operative combination immunotherapy with Talimogene Laherparepvec (T-VEC)/Pembrolizumab given prior to complete lymph node dissection in resectable stage 3 cutaneous melanoma with clinically apparent lymph node metastases.
Eligibility: 18 Years to · All · * 18 years of age, any race or sex, who have pathologically confirmed cutaneous melanoma
* ECOG performance status of 0 or 1
* Adequate hematologic, hepatic, renal and coagulation function
* Must have measurable disease and have an injectable target lymph node for intralesional therapy administration
* Primary melanoma has been resected
* Pathologically confirmed resectable stage III disease, clinically apparent. Resectability is at the discretion of the treating surgeon who is a melanoma specialist.
* Stage III disease can be at time of diagnosis of primary melanoma or a recurrence after initial treatment of stage I-II disease.
* BRAF mutant or wild type allowed (mutations status not necessary for enrollment)
* Signed, written informed consent
NCT05655312Phase 1, Phase 2Recruiting
Perspective Therapeutics · University of California Irvine, Orange, California
In this first-in human, phase I/IIa study, the safety and efficacy of \[212Pb\]VMT01, an alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R) is being evaluated as a monotherapy and in combination with nivolumab in subjects with unresectable and metastatic melanoma.
Eligibility: 18 Years to 90 Years · All · * Ability to understand and willingness to provide informed consent, willingness to comply with all study procedures for the duration of the study
* Aged ≥ 18 years
* Diagnosed with unresectable Stage III or Stage IV metastatic or recurrent melanoma
* Previously progressed (radiological progression) on at least one approved systemic therapy for advanced melanoma
* Uptake of \[68Ga\]VMT02 or \[203Pb\]VMT01 by PET or SPECT imaging observed in at least one melanoma tumor site using quantitative imaging analysis compared to reference normal tissue
* Subjects on prior intravenous therapy (e.g., chemotherapy or checkpoint inhibitors), or prior oral therapy (e.g.,proto-oncogene B-RAF or mitogen-activated extracellular signal-regulated kinase inhibitors) who demonstrate MC1R positivity during screening are eligible for enrollment, provided that they undergo a wash-out period of 21 days, or 7 days, respectively, prior to Cycle 1 Day 1 treatment with \[212Pb\]VMT01.
* Presence of measurable disease by RECIST v1.1 assessed within 45 days prior to the first dose of \[212Pb\]VMT01 on Cycle 1 Day 1
* Ability to lie flat and still for up to two hours for imaging scans; moderate conscious sedation allowed if indicated
* For females of reproductive potential: agree to use of highly effective contraception and refrain from donating eggs (ova, oocytes) for the purpose of reproduction starting from screening, during treatment with \[212Pb\]VMT01 and/or nivolumab, and for at least 6 months after the last dose of \[212Pb\]VMT01 and/or nivolumab, whichever is administered last
* For males of reproductive potential: agree to use of condoms or other methods to ensure effective contraception and refrain from donating sperm starting from screening, during treatment with \[212Pb\]VMT01 and/or nivolumab, and for at least 6 months after the last dose of \[212Pb\]VMT01 and/or nivolumab, whichever is administered last
* Eastern Cooperative Oncology Group performance score of \< 2 at Screening
* Life expectancy of at least 3 months after Cycle 1 Day 1
* Satisfactory organ function determined by laboratory testing
NCT05527795Phase IIRecruiting
Hospices Civils de Lyon · Centre Hospitalier Lyon Sud, Pierre-Bénite
Surgical excision is the treatment of choice for stage II, III and resectable stage IV melanoma and is curative in most cases. Given the recent success of immunotherapy for the treatment of patients with advanced metastatic melanoma, the use of immunotherapy has been evaluated in the adjuvant setting for patients at high risk of recurrence. In this context, Nivolumab prolonged Recurrence-Free Survival (RFS) while reducing toxicity compared with Ipilimumab in a phase III clinical trial, and was subsequently FDA-approved in December 2017 for adjuvant treatment of locally advanced melanoma with metastatic lymph node involvement after resection of cutaneous lesions. While a fraction of patients benefit from adjuvant PD-1 immunotherapy, approximately 40% of patients are still relapsing despite this adjuvant treatment, without being able to identify them early and with poor understanding of resistance mechanisms. Additionally, about 15% of the patients will develop serious adverse effects driven by immunotherapy and often discontinuing or even contraindicating the onset of subsequent treatments, hence affecting global patients care. It is therefore of prime importance to identify clinical features able to predict response and toxicities to adjuvant immunotherapy in melanoma.
Eligibility: 18 Years to · All · * Patients diagnosed with stage II, III or IV (resected) melanoma
* Treated by surgery and adjuvant immunotherapy between January 1st of 2019 and January 1st of 2029
* Gave informed consent to allow the use of biological samples for research purpose
* Has read the information sheet regarding this study
* With tumor samples available at the biobank center
NCT06952400Phase IIRecruiting
National Health Research Institutes, Taiwan · Taipei Veterans General Hospital, Taipei, Taiwan/Taipei
Cutaneous melanoma is the most aggressive malignancy in skin cancers. Cutaneous melanoma is a rare disease in Taiwan with an incidence rate of around 1/100,000. Acral lentiginous melanoma is the most common subtype and comprises more than half of cutaneous melanoma in Asia including Taiwan but only 1% in Caucasians. In addition, mucosal melanoma accounts for more than 20% of malignancy melanoma in Taiwan but only 1% in Caucasians. Acral and mucosal melanomas have distinct epidemiological, clinical, pathological and genetic features from non-acral melanoma which is commonly seen in Western countries. Comparing with melanoma in Caucasians, Asian melanoma has higher recurrence rate after primary surgery, lower response rate to immunotherapy, and shorter progression-free survival for immunotherapy and targeted therapy leading generally poor survival outcomes regardless stage.
Eligibility: 18 Years to · All · 1. Age \> 18 years old
2. Pathologically confirmed melanoma. (Patients with additional malignancies requiring treatment or follow-up are allowed. Only treatment for melanoma should be recorded).
3. ECOG performance status \< 3
4. Cohort 1(early acral melanoma): melanoma, stage I/II; Cohort 2 (locally advanced acral melanoma): melanoma, stage III, resectable; and Cohort 3 (advanced): unresectable / metastatic melanoma, stage III/IV or recurrent melanoma (unresectable). Staging is based on AJCC Cancer Staging System 8th edition). The patients with advanced melanoma with available comprehensive NGS report are included in cohort 4.
5. Willingness to provide archival or newly obtained tumor tissues for this study proposal
6. Life expectancy more than 3 months -
7. Patients fully understand the protocol with the willingness to have regular follow-up
NCT07288112Phase 1, Phase 2Recruiting
Diakonos Oncology Corporation · The University of Alabama at Birmingham, Birmingham, Alabama
The goal of this clinical trial is to learn if DOC1021 + pIFN will be safe and will lead to tumor responses in patients with refractory melanoma. DOC1021 is a dendritic cell immunotherapy derived from a patient's own blood cells and loaded with antigens from the patient's tumor in the form of tumor lysate and mRNA. The goal is to stimulate a T cell immune response that eliminates tumor cells.
The study consists of two components: an initial phase I safety study to confirm safety/tolerability of the treatment regimen, and, subsequently, a single-arm phase II cohort to assess efficacy of the treatment regimen.
All participants will:
* Undergo a leukapheresis collection (take filgrastim subcutaneously x 5 doses, if clinically necessary, leading up to collection)
* Receive two doses of DOC1021 under image guidance 2 weeks apart
* Receive subcutaneous pIFN injections weekly for a total of 4 doses in parallel with the DOC1021 injections
* Undergo an optional image-guided perinodal DOC1021 booster injection approximately 6 months after the first DOC1021 dose along with additional subcutaneous pIFN injections at time of the booster and the subsequent week for a total of 2 pIFN doses
* Visit the clinic regularly to assess quality of life, symptoms, medication use, imaging, bloodwork, and to receive optional treatment with anti-PD1 agents
Eligibility: 18 Years to · All · 1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and avail-ability for the duration of the study
3. Age 18 years or older
4. Patients diagnosed with unresectable or metastatic melanoma and progressed following ≥1 prior systemic therapy including anti-PD-1 (i.e., refractory to anti-PD-1). Refractory defined as primary or secondary resistance as per SITC guidelines, except that confirmatory scan not required if clinical progression requiring surgery or radiation to relieve symptoms
5. Willing and able to withhold anti-PD-1 treatment from the time of enrollment through at least 6 weeks after the first DOC1021 administration
6. One or more lesions available for biopsy or resection expected to yield at least 50 mg and preferably 100 mg of tumor for generating DOC1021 and at least 1 measurable target tumor lesion evaluable after DOC1021 by RECIST version 1.1.
7. Brain metastases allowed if stable after prior treatment
8. Ability to receive leukapheresis (with filgrastim if clinically indicated) and perinodal injections of DOC1021 near regional nodes + weekly pIFN x 4 weeks (i.e., sufficient clinical stability and anticipated life expectancy to complete the treatment period and allow time for an immune response to develop).
9. Females of reproductive potential must have a negative serum pregnancy test and agree to use effective contraception (as deter-mined appropriate for the patient by the investigator) during study treatment.
10. Adequate kidney, liver, bone marrow function, and immune function, as follows:
1. Hemoglobin ≥ 8.0 gm/dL (use of transfusion or other intervention to achieve is acceptable)
2. Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
3. Platelet count ≥ 75,000/mm3
4. Calculated creatinine clearance (CrCl) \> 30 mL/min using Cockcroft and Gault formula:
i. For males = (140 - age\[years\]) x (body weight \[kg\]) / (72 x serum creatinine \[mg/dL\]) ii. For females = 0.85 x value from male formula e. Total bilirubin ≤ 1.5 times upper limit of normal (ULN) except in patients with Gilbert's disease for which total bilirubin must be ≤ 3 times ULN f. Aspartate transaminase AST (SGOT) and alanine aminotransferase ALT (SGPT) ≤ 3 times the ULN (or ≤ 5.0 × ULN if liver metastases)
11. Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1
NCT07564570NARecruiting
Universitätsklinikum Hamburg-Eppendorf · University Medical Center Hamburg-Eppendorf, Hamburg, Free and Hanseatic City of Hamburg
The aim of this research project is to determine whether a short bout of physical exercise immediately before the start of immunotherapy (Nivolumab and Ipilimumab) is feasible and has a positive effect on the effectiveness of immunotherapy. It is known that short-term physical exercise leads to marked changes in the innate and adaptive immune system. These changes-specifically an increase in natural killer (NK) cells and cytotoxic T cells-are associated with a better response to immunotherapy.
The patient population selected for this study consists of patients with advanced-stage melanoma who are receiving Nivolumab and Ipilimumab.
First, we aim to assess whether such an intervention is feasible in a large proportion of patients, as many patients experience disease-related and treatment-related side effects.
Secondary objectives are to demonstrate that the exercise intervention positively influences the immune system and that this, in turn, leads to an improved response to therapy, thereby positively affecting patient survival, improving quality of life, and reducing treatment-related side effects.
Eligibility: 18 Years and older · All · * Histologically confirmed metastatic malignant melanoma with an indication for immunotherapy (Nivolumab and Ipilimumab).
* The participant provides written informed consent for the study.
* The participant is at least 18 years of age on the day the informed consent is signed.
* No prior systemic anticancer therapy for metastatic disease (e.g., cytotoxic or targeted agents).
* ECOG (Eastern Cooperative Oncology Group) performance status score of ≤ 2.
* No physical impairment that would preclude participation in physical exercise.
NCT06529822Phase 1Recruiting
Washington University School of Medicine · AdventHealth, Orlando, Florida
This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine strategy in patients with solid tumors and molecular residual disease. The hypothesis of the trial is that synthetic long peptide personalized cancer vaccines will be safe and capable of generating measurable neoantigen-specific T-cell responses enabling ctDNA clearance. The personalized cancer vaccines are composed of synthetic long peptides corresponding to prioritized cancer neoantigens and will be co-administered with poly-ICLC.
Eligibility: 18 Years to · All · Inclusion Criteria Cohort #1:
* Age ≥ 18 years.
* ECOG performance status ≤ 2 (Karnofsky ≥ 60%).
* Histologically confirmed muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (renal pelvis and/or ureter).
* Patients with carcinomas showing mixed histologies are required to have a dominant transitional cell pattern.
* Complete surgical resection of MIBC (R0) or upper tract urothelial carcinoma (renal pelvis and/or ureter). Tumor, nodes, metastases (TNM) classification (based on the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th ed.) at pathological examination of surgical resection specimen as follows: ypT0N0M0, pT2-4N0M0, or pT0-4aN+M0.
* Patient must have fully recovered from surgical resection in the opinion of the treating MD.
* ctDNA positive result as identified by Signatera.
* Radiologic confirmation (by conventional imaging) of absence of residual disease and absence of metastasis.
* Adequate bone marrow and organ function as defined below:
* WBC ≥ 1.5 K/cumm
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 50 K/cumm
* Hemoglobin ≥ 8.0 g/dL
* Total bilirubin ≤ 1.5 x IULN
* AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
* Creatinine clearance \> 30 mL/min by Cockcroft-Gault
* The effects of synthetic long peptide personalized cancer vaccines and Hiltonol on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 5 months after completion of study interventions. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* No concurrent investigational therapies outside of this protocol are allowed.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria Cohort #1:
* Receiving any other investigational agents, or planning to receive other investigational agents as part of neoadjuvant therapy. Patients who have received perioperative neoadjuvant chemotherapy and immunotherapy, including enfortumab vedotin plus pembrolizumab (EV+P), are allowed.
* Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
* A psychiatric illness or social situations that would limit compliance with study requirements as determined by the investigator from the medical history, physical exam, and/or medical record.
* Prior or currently active autoimmune disease requiring management with immunosuppression. This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication (e.g., corticosteroids) which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines. In the case of asthma or chronic obstructive pulmonary disease taking inhaled corticosteroids that does not require daily systemic corticosteroids is acceptable. Additionally, local acting steroids (topical, inhaled, or intraarticular) will be allowed. Patients on intermittent or short course steroids will be allow if the dose does not exceed 4 mg of dexamethasone (or equivalent) per day for \> 7 consecutive days. Premedication for chemotherapy does not apply to this criterion and may be administered as per SOC practice. Any patients receiving steroids should be discussed with the PI to determine if eligible.
* Known HIV-positive status.
* History of positive test for Hep
NCT06214156Phase 1, Phase 2Recruiting
Shanghai Pharmaceuticals Holding Co., Ltd · Beijing Cancer Hospital, Beijing
This clinical study evaluated the tolerability, safety and preliminary efficacy of T3011 in subjects with advanced melanoma.
Eligibility: 18 Years to · All · 1. Subjects with advanced melanoma;
2. At least one measurable lesion;
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
4. Expected survival \> 12 weeks;
5. Laboratory inspection meets the requirements;
6. For women of childbearing potential, the serum pregnancy test results must be negative within 7 days prior to the first dose，and effective contraceptive measures must be taken from signing the informed consent form (ICF) until at least 6 months after the last dose;
7. Male subjects of childbearing potential agree to use effective contraception from signing the ICF until at least 6 months after the last dose; In addition, male subjects must agree not to donate sperm during this period;
8. Understand and voluntarily sign the ICF，willing and able to comply with all experimental requirements.
NCT06508567NARecruiting
University Health Network, Toronto · Princess Margaret Cancer Centre, Toronto, Ontario
This is an interventional, single-centre, single-arm, non-randomized, prospective, feasibility trial investigating salvage MR-guided High-Dose-Rate brachytherapy for prostate bed recurrence after postoperative radiotherapy.
Eligibility: 18 Years to · Male · 1. Patients who received previous RT to the prostate bed +/- pelvic nodal regions
2. Prostate-bed recurrence identified by biopsy and/or MRI and/or PSMA-PET scan
3. At least two continuous PSA elevations post RT and PSA above 0.2 ng/dl
4. With or without ADT PSA doubling time from nadir greater than 6 months
5. ECOG 0-2
6. Age greater than 18 years
NCT06496581Phase 3Recruiting
UNICANCER · Institut de Cancérologie de l'Ouest, Angers
PEACE-6 Poor Responders is an international, multicenter, open-label, controlled, randomized, phase III trial to evaluate the efficacy and safety of 177Lu-PSMA-617 when administered on top of the ongoing standard systemic treatment compared to standard systemic treatment alone in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who do not present with a satisfactory response characterized by a serum prostatic specific antigen (PSA) level of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation for mHSPC (i.e. poor responders) in the absence of evidence of cancer progression (including a rising PSA level).
Eligibility: 18 Years to 80 Years · Male · All of the following criteria must be met ahead of randomization to satisfy trial eligibility requirements:
1. Signed a written informed consent form prior to any trial specific procedures.
Note: In case of physical incapacitation, a trusted representative of their choice, which is not the Investigator or sponsor, can sign on the behalf of the patients.
2. Aged ≥18 years old
3. Life expectancy \> 6 months as per investigator estimate
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
5. Men with histologically or cytologically confirmed adenocarcinoma of the prostate
6. De novo metastatic disease defined by clinical or radiographic evidence of metastases at diagnosis (i.e. before any treatment started). If not available, a more recent imaging can be used
7. Measurable disease or bone lesions evaluable according to PCWG3 criteria. Patients with doubtful bone metastases are not eligible
8. A pre-randomization 68Ga-PSMA-11 PET/CT scan performed within 4 weeks prior to randomization in the trial.
FDG PET scan is not required for this protocol. All patients will be treated independently from the results of pre-randomization PSMA PET scan: patients with PSMA-positive or PSMA-negative disease according to PROMISE 2.0 criteria are eligible.
9. Have 6 to 8 months of previous AND ongoing standard systemic treatment for prostate cancer consisting in either:
* ADT with an androgen receptor signaling inhibitor (ARSI) (i.e., abiraterone (plus prednisone), or apalutamide or enzalutamide) ± radiotherapy \*\*
* ADT with docetaxel\* plus an ARSI (i.e. abiraterone (plus prednisone), or darolutamide,) ± radiotherapy\*\*
Note:
\*Docetaxel must have been stopped at least 4 weeks ahead of randomization.
\*\* Previous radiotherapy to the primary tumor and/or to the metastases is accepted as long as it was not PSMA-based and must has been completed at least 4 weeks ahead of randomization.
10. Stable or declining PSA level but not a rising one
11. Serum PSA of ≥ 0.2 ng/mL at 6 to 8 months after systemic treatment initiation
12. Testosterone level \< 50 ng/dl or \< 1.7 nmol/L
13. Be fit enough for 177Lu-vipivotide tetraxetan treatment:
* Adequate bone marrow function: hemoglobin ≥90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization), absolute neutrophil count ≥1.5 x10⁹/L, platelet count \>100 x10⁹/L
* Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0 x upper limit of normal (ULN), or ≤ 5.0 x ULN in the presence of liver metastases; bilirubin \<1.5 x ULN (unless known or suspected Gilbert syndrome, then \<3 x ULN is permitted)
* Adequate renal function: calculated creatinine clearance ≥ 50 ml/min (using the MDRD or CKD EPI method).
14. For sexually active men with female partners of reproductive potential or with pregnant women, agreement to use a condom with another effective contraceptive method during trial participation and up to 14 weeks after study treatment completion.
15. Affiliated to the social security system or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials).
16. Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.
