Zimberelimab Plus Metformin for Recurrent Ovarian Clear Cell Carcinoma

Sponsor

Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05759312

Collaborator

(none)

Enrollment

Arm

23.1

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ovarian Clear Cell Carcinoma	Drug: Zimberelimab Drug: Metformin Hydrochloride	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Zimberelimab Combined With Metformin in the Treatment of Recurrent Ovarian Clear Cell Carcinoma: A Pilot Study

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: zimberelimab plus metformin Patients 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.	Drug: Zimberelimab Zimberelimab 240mg IV every 2 weeks Other Names: Anti PD-1 Drug: Metformin Hydrochloride Metformin 2000mg PO QD Other Names: Metformin

Arm

Intervention/Treatment

Experimental: zimberelimab plus metformin

Patients 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.

Drug: Zimberelimab

Zimberelimab 240mg IV every 2 weeks

Other Names:

Anti PD-1

Drug: Metformin Hydrochloride

Metformin 2000mg PO QD

Other Names:

Metformin

Outcome Measures

Primary Outcome Measures

Objective response rate [Up 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

Progression-free survival [Up to 2 years]
The time from entry into the study to the diagnosis of the first progression or recurrence or death, whichever occurs first
Overall survival [Up to 2 years]
The time from date of randomization until the date of death from any cause or last follow-up
Disease control rate [Up 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
Duration of response [Up to 2 years]
The time interval from the first record of disease response to disease progression or death (whichever occurs first)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Up 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 recurrence [Up 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.)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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