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Zimberelimab Plus Metformin for Recurrent Ovarian Clear Cell Carcinoma

Phase 1
Not yet recruiting
Conditions
Ovarian Clear Cell Carcinoma
Interventions
Registration Number
NCT05759312
Lead Sponsor
Fudan University
Brief Summary

This study aims to evaluate the safety and effectiveness of zimberelimab combined with metformin in treating relapsed/persistent ovarian clear cell carcinoma.

Detailed Description

Ovarian clear cell carcinoma (OCCC) is one of the rare subtypes of ovarian cancer, yet its prognosis is extremely poor. Previous studies indicate that PD-1 inhibitors may have clinical benefits for OCCC patients. This single-arm, single-center, pilot study evaluates the safety and effectiveness of zimberelimab combined with metformin in treating relapsed/persistent ovarian clear cell carcinoma.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
20
Inclusion Criteria
  • Age ≥ 18 years to ≤ 75 years
  • Pathologic confirmed ovarian clear cell carcinoma
  • Patients with recurrent or persistent ovarian clear cell carcinoma must have at least one-line pretreated platinum-containing chemotherapy
  • According to the definition of RECIST1.1, the patient must have measurable lesions
  • PD-L1 Combined Positive Score ≥ 1
  • ECOG performance status of 0 to 2
  • Adequate bone marrow, liver, and renal function to receive combined immunotherapy
  • Written informed consent
Exclusion Criteria
  • Histological evidence of non-ovarian clear cell carcinoma
  • Lack of tumor samples (archived and/or recently obtained)
  • Previous administration of immunotherapy
  • Patients have been vaccinated with the live vaccine or received anti-tumor treatment within 4 weeks before the first administration
  • An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) within 2 years before the first administration
  • Synchronous or metachronous (within 5 years) malignancy other than carcinoma in situ or breast cancer (without any signs of relapse or activity) Symptomatic or uncontrolled visceral metastases that require simultaneous treatment
  • Patients are known to be allergic to the active ingredients or excipients of zimberelimab or metformin
  • Known human immunodeficiency virus (HIV) infection history (HIV 1/2 antibody positive).
  • Untreated active hepatitis B (defined as HBsAg positive and the number of copies of HBV-DNA detected at the same time is greater than the upper limit of the normal value of the laboratory department of the research center)
  • Contraindications to metformin: kidney dysfunction or abnormal creatinine from any cause; acute or metabolic acidosis

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
zimberelimab plus metforminZimberelimabPatients will start metformin at 1,000mg by mouth once daily during a 7-day induction period prior to starting zimberelimab. The dose will be increased by 500mg every 7 days until reaching the target dose of 2000mg. Zimberelimab will be administered at a fixed dose of 240 mg IV every 14 days. Treatment will continue until disease progression confirmed by RECIST criteria v1.1, intolerable toxicity, or withdrawal of consent.
zimberelimab plus metforminMetformin HydrochloridePatients will start metformin at 1,000mg by mouth once daily during a 7-day induction period prior to starting zimberelimab. The dose will be increased by 500mg every 7 days until reaching the target dose of 2000mg. Zimberelimab will be administered at a fixed dose of 240 mg IV every 14 days. Treatment will continue until disease progression confirmed by RECIST criteria v1.1, intolerable toxicity, or withdrawal of consent.
Primary Outcome Measures
NameTimeMethod
Objective response rateUp to 2 years

The proportion of patients with complete response (CR) and partial response (PR) assessed by the investigator in accordance with the RECIST 1.1 criteria

Secondary Outcome Measures
NameTimeMethod
Duration of responseUp to 2 years

The time interval from the first record of disease response to disease progression or death (whichever occurs first)

Overall survivalUp to 2 years

The time from date of randomization until the date of death from any cause or last follow-up

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0Up to 2 years

The adverse event assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Patterns of subsequent recurrenceUp to 2 years

The number and sites of subsequent recurrence, including pelvic, abdominal, retroperitoneal lymph nodes, hepato-celiac lymph nodes and distant metastases and ascites, etc.)

Disease control rateUp to 2 years

The proportion of patients who achieved complete response (CR) or partial response (PR) or stable disease (SD) assessed by the investigator in accordance with the RECIST 1.1 criteria

Progression-free survivalUp to 2 years

The time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first

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