NCT06323239Phase 2Recruiting
Sun Yat-sen University · Sun Yat-sen University Cancer Center, Guangzhou, Guangdong
This is a prospective, single-arm, phase II clinical trial. The purpose of this study is to evaluate the efficacy and adverse effect of SBRT and LDRT combined with programmed death 1 (PD-1) antibody and chemotherapy in recurrent/metastatic nasopharyngeal carcinoma patients.
Eligibility: 18 Years to 75 Years · All · * Diagnosed as recurrence/metastatic NPC
* Histopathological diagnosis of NPC(WHO II/III)
* ECOG 0-1 point
* No treatment to r/mNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
* No contraindications to immunotherapy and chemoradiotherapy;
* At least one lesion could receive SBRT safely;
* Subject must have a measurable target lesion based on RECIST v1.1;
* Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/ L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
* Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
* Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
* Take effective contraceptions during and three months after treatment;
* Patients must be informed of the investigational nature of this study and give written informed consent.
NCT06029270Phase 2Recruiting
National Cancer Institute (NCI) · Kaiser Permanente Dublin, Dublin, California
This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy after initial treatment for nasopharyngeal cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. The usual approach of treatment is initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is finished, patients may continue to receive additional immunotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend the time without the tumor cells growing or spreading longer than the usual approach in patients with recurrent or metastatic nasopharyngeal cancer.
Eligibility: 18 Years to · All · Inclusion Criteria:
* PRIOR TO STEP 1 REGISTRATION:
* Pathologically (histologically or cytologically) proven diagnosis of nasopharyngeal carcinoma (NPC) that has recurred locoregionally and/or is present at distant sites. Patients who present with metastatic disease (de novo) at diagnosis are also eligible. For locoregional recurrence, the disease must not be amenable to potentially curative surgery or re-irradiation. Eligible patient must have the following characteristics:
* Tumor showing (histological/cytological) Epstein-Barr encoded ribonucleic acid (EBER)-positivity (e.g., In situ hybridization, immunohistochemistry) or
* A known history of detectable plasma EBV DNA (via a polymerase chain reaction \[PCR\]-based assay) at any time point since the initial diagnosis of NPC.
* Measurable disease as defined by RECIST 1.1 criteria. Lesion(s) that have been irradiated previously can be counted as measurable as long as radiological progression after the prior radiation therapy has been demonstrated.
* Contrast enhanced CT scan of the chest. The contrast enhanced CT component of a whole-body PET-CT is also acceptable. The plain (non-contrast) CT component of a PET-CT is not acceptable.
* CT the abdomen and pelvis, if clinically indicated (diagnostic quality with contrast, unless contraindicated).
* Patients with known locoregional disease must have contrast enhanced MRI or CT of the nasopharynx and neck as this disease site(s) may be assessed as target lesions. For patients without known locoregional disease, imaging of the nasopharynx and neck is optional.
* Symptomatic and active brain metastases and/or leptomeningeal metastasis on CT and/or MRI imaging: Patients who have prior therapies for brain and leptomeningeal metastasis or cord/cauda compression who are clinically stable for \>= 2 months prior to registration and have discontinued systemic steroids therapy (\> 10 mg/day prednisone or equivalent) \> 4 weeks prior to registration are eligible.
* Patients with base of skull involvement by NPC are allowed unless their disease is directly invading the brain parenchyma, associated with clinical symptoms and/or significant vasogenic edema on radiological imaging.
* Age \>= 18 years.
* Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2.
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
* Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3.
* Platelets \>= 100,000 cells/mm\^3.
* Hemoglobin (Hgb) \>= 8.0 g/dL (Transfusion is accepted. Erythropoietin dependency not accepted.).
* Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN) or direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN. Patients with known Gilbert's disease who have serum bilirubin level =\< 3 × ULN may be enrolled.
* Alanine transaminase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 × ULN (=\< 5 × ULN for patients with liver metastases).
* Serum creatinine =\< 1.5 × ULN or calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation \>= 30 mL/min for patients with serum creatinine levels \> 1.5 × ULN. Cisplatin or carboplatin may be used at the discretion of the investigator - except for patients with CrCl between 30-50 mL/min, for whom carboplatin should be used instead of cisplatin. CrCl must be \> 50 mL/min for cisplatin to be used.
* Albumin-adjusted calcium level based on corrected calcium equation =\< 1.5 × ULN (patients are allowed to have treatment for hypercalcemia prior to starting treatment).
* No prior systemic treatment of palliative intent for recurrent/metastatic (R/M) NPC including cytotoxic chemotherapy. Prior treatment for non-recurrent and non-metastatic NPC is allowed. Syste
NCT06394570Phase 1, Phase 2Recruiting
University of Texas Southwestern Medical Center · UT Southwestern Medical Center, Dallas, Texas
STAR-EV will evaluate the combination of enfortumab vedotin plus radiotherapy (RT) as neoadjuvant treatment for muscle invasive bladder cancer prior to radical cystectomy surgery. The study will use "dose escalation" to evaluate the safety and efficacy of study treatment at three dose regimens:
Level 0: EV treatment followed by RT to the bladder Level 1: EV treatment with RT starting on Cycle 2, Day 15 Level 2: EV treatment with RT starting on Cycle 1, Day 15
Following completion of EV+RT neoadjuvant therapy, all subjects will undergo surgery as part of routine care.
Eligibility: 18 Years to · All · 1. Urothelial carcinoma of the urinary bladder stage cT2-4a (AJCC 8th edition) N0M0 planned for radical cystectomy. Mixed cell types with variant histologies (including squamous, plasmacytoid, adenocarcinoma, sarcomatoid, micropapillary, nested, and lipid cell variants) are allowed as long as any urothelial histology is present (i.e. -not 100% variant histology). Small cell/neuroendocrine component is excluded.
2. Ineligibility for cisplatin-based chemotherapy based on treating physician assessment and any of the following "Galsky criteria": renal insufficiency (Creatinine Clearance \<60ml/min by standard institutional calculation method), \>=grade 2 peripheral neuropathy, \>=grade 2 hearing loss, New York Heart Association (NYHA) class III heart failure; a combination of these; or patient refusal.
3. Age \>=18.
4. Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
5. Adequate organ and marrow function as defined below:
•Hematologic:
-Absolute neutrophil count (ANC) \>=1500/mm3
* Platelet count \>=100x109/L
* Hemoglobin ≥ 9 g/dL
•Hepatic:
* Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
•Renal:
* No end stage renal disease requiring dialysis allowed
6. All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 months following completion of study neoadjuvant therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
6a. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
7.Ability to understand and the willingness to sign a written informed consent.
NCT06040970Phase 1, Phase 2Recruiting
Icahn School of Medicine at Mount Sinai · Icahn School of Medicine at Mount Sinai Division of Hematology and Medical Oncology, New York, New York
This is an open-label, Phase 1 study with a dose expansion cohort of Sacituzumab Govitecan in Combination with Cisplatin in Platinum Sensitive Recurrent Ovarian and Endometrial Cancer. The goal of the study is to determine the optimal dose of sacituzumab govitecan for use in combination with cisplatin for treatment of epithelial ovarian and endometrial cancers.
Eligibility: 18 Years to · Female · Eligibility waivers are not permitted. Subjects must meet all of the inclusion and exclusion criteria to be registered to the study. Study treatment may not begin until a subject is registered.
* Pathologic (histology or cytology) confirmed diagnosis of epithelial ovarian cancer or endometrial cancer
* Radiographic evidence of recurrent epithelial ovarian cancer (ovarian, fallopian tube, or primary peritoneal cancer) or endometrial cancer that is "platinum-sensitive," defined as progression of disease beyond 6 months from the last dose of platinum-based chemotherapy
* Female, age ≥ 18 years
* World Health Organization (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
* Patient has measurable disease (at least one lesion that can be accurately assessed repeatedly by CT) as evidenced on pre-treatment baseline CT of Chest/Abdomen/Pelvis or PET/CT, or evaluable disease
* Adequate hematologic counts, as defined below, without transfusion or growth factor support within 2 weeks of study drug initiation:
* Hemoglobin ≥ 8.5 g/dL
* Absolute neutrophil count ≥ 1500/mm3
* Platelets ≥ 100,000/μL
* Adequate organ function as defined below:
* Total bilirubin ≤ 1.5 ULN
* AST(SGOT)/ALT(SPGT) ≤ 2.5x ULN or ≤ 5 x ULN if known liver metastases
* Serum albumin \> 3 g/dL
* Creatinine clearance ≥ 50 mL/min per the Cockcroft-Gault equation
* Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
o A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
* Ability to understand and the willingness to sign a written informed consent.
NCT04811703Phase 1Recruiting
Hospices Civils de Lyon · Hôpital Claude Huriez - Chirurgie générale et digestive, Lille
Women with a history of tumor response insufficient to allow complete cytoreductive surgery after three cycles of prior neoadjuvant systemic carboplatin-paclitaxel chemotherapy will be prospectively enrolled in this phase I study. After providing written informed consent and confirmation of unresectable disease by multidisciplinary assessment, patients will undergo three cycles of combined chemotherapy consisting of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with doxorubicin and cisplatin at escalating dose levels, combined with systemic intravenous chemotherapy using carboplatin and paclitaxel at standard doses. Treatment cycles will last 28 days, with PIPAC administered on Day 1 and systemic chemotherapy on Day 8, for a maximum of three cycles in the absence of unacceptable toxicity.
Dose escalation of PIPAC chemotherapy will follow a Continual Reassessment Method (CRM) algorithm. The first patient will be treated at the lowest dose level, and subsequent patients will receive the recommended dose according to the CRM, conditional on the occurrence of dose-limiting toxicity (DLT) observed during Cycle 1. From dose level 7 onward, corresponding to cisplatin and doxorubicin doses associated with an increased risk of renal toxicity, sodium thiosulfate will be systematically administered prior to each PIPAC procedure for its nephroprotective effect, in accordance with the cisplatin dose level and current clinical practice.
The primary objective of the study is to determine the maximum tolerated dose (MTD) of doxorubicin-cisplatin administered by PIPAC and to define the recommended dose for a subsequent phase II trial. DLTs will be actively collected and reviewed as soon as they are identified during the first treatment cycle.
Secondary objectives include evaluation of pathological response, radiological tumor response, and changes in the extent of peritoneal disease following combined chemotherapy, as well as characterization of the pharmacokinetics of PIPAC-administered drugs. Additional exploratory objectives include assessment of the KELIM parameter as a predictive marker of sensitivity to combined chemotherapy and evaluation of the overall safety profile of the treatment strategy.
On Day 1 of the first treatment cycle, blood samples will be collected for pharmacokinetic analysis of doxorubicin and cisplatin. Serum CA-125 levels will be measured before each intraperitoneal or intravenous chemotherapy administration throughout the study. At the end of combined chemotherapy, radiological tumor assessment by CT scan or MRI and a final CA-125 measurement will be performed. Patients achieving complete response, partial response, or stable disease according to RECIST v1.1 criteria will undergo re-evaluation for surgical resectability. If complete cytoreductive surgery is deemed feasible, surgery will be scheduled with a post-operative follow-up visit planned one month later. Patients with progressive or persistently unresectable disease will discontinue study participation.
Eligibility: 18 Years to 75 Years · Female · * Age ≥ 18 years and ≤ 75 years;
* ECOG Performance Status 0-2;
* Histologically confirmed epithelial carcinoma of the ovary, fallopian tubes, or peritoneum, FIGO stage IIb to IVa, with a tumor response after three cycles of carboplatin-paclitaxel that does not correspond to disease progression but is insufficient to allow complete cytoreductive surgery, as assessed by the investigators after multidisciplinary tumor board discussion and validation;
* Adequate hematological function:
* Absolute neutrophil count \> 1,500/mm³ (or 1.5 × 10⁹/L);
* Hemoglobin ≥ 9.0 g/dL;
* Platelet count \> 100 × 10⁹/L;
* Adequate renal and hepatic function:
* Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or estimated glomerular filtration rate ≥ 60 mL/min/1.73 m² (CKD-EPI equation);
* Total bilirubin ≤ 1.5 × ULN;
* AST and ALT ≤ 1.5 × ULN (≤ 5 × ULN in patients with liver metastases);
* No unstable medical conditions, including myocardial infarction within 6 months prior to study entry, congestive heart failure, unstable angina, active cardiomyopathy, unstable arrhythmia, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer disease, or any condition that could be worsened by the study treatment or impair compliance, as judged by the investigator;
* Written informed consent obtained prior to any study-specific procedures;
* Patient affiliated with a national health insurance system.
NCT06721286Phase 2Recruiting
Tianjin Medical University Cancer Institute and Hospital · Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin Municipality
This study was a randomized controlled trial to evaluate the efficacy and safety of toripalimab combined with GemCis (gemcitabine and cisplatin) as preoperative neoadjuvant therapy for resectable ICC at high risk of recurrence.
Eligibility: 18 Years to · All · 1. Age ≥ 18, male or female;
2. Pathological diagnosis confirmed intrahepatic cholangiocarcinoma, which could be resected surgically; One of the following conditions shall be met:
2.1 Single tumor, diameter greater than 5cm (T1b) 2.2 Single tumor with vascular invasion (T2), multiple tumors ≤ 3 2.3 Tumor penetrating visceral peritoneum (T3) or directly invading surrounding organs (T4) 2.4 Suspicious lymph node metastasis in Zone 8, 12 or 13
3. Can not received systemic treatment before participating in the study;
4. ECOG PS score 0-1;
5. The main organs function normally, and there is no serious blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immune deficiency diseases.
6. Laboratory inspection shall meet the following requirements:
Women of childbearing age must have a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; For men, they should be surgically sterilized or agree to use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug.
7. The patient voluntarily participated and signed the informed consent form;
8. It is expected that the compliance is good, and the efficacy and adverse reactions can be followed up according to the requirements of the scheme.
