Ovarian Cancer Clinical Trial
Official title:
Pamiparib in Combination With Surufatinib in Patients With Platinum-resistant Ovarian Cancer Who Received Prior Poly (ADP-ribose) Polymerase (PARP) Inhibitors: a Multicenter, Single-arm, Phase Ib/II Trial
A number of studies suggest that the combination of PARP inhibitors and antiangiogenic agents produce synergistic activities. Pamiparib is a small molecule inhibitor selectivity for both PARP1 and PARP2. Surufatinib is a novel small-molecule inhibitor that simultaneously targets tumor angiogenesis (via Vascular Endothelial Growth Factor Receptor [VEGFR]1, VEGFR 2, VEGFR3 and Fibroblast Growth Factor Receptor 1 [FGFR1]) and immune evasion (via Colony Stimulating Factor 1 Receptor [CSF1R]). In this trial, we aimed to evaluate the efficacy, safety and tolerability of pamiparib in combination with surufatinib in patients with platinum-resistant ovarian cancer who received prior PARP inhibitors.
Status | Recruiting |
Enrollment | 38 |
Est. completion date | August 10, 2025 |
Est. primary completion date | August 10, 2024 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: 1. Signed Informed Consent Form; 2. Histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; 3. Platinum-resistant disease, defined as progression within 6 months from completion of most recent platinum-containing therapy. Subject may have been treated with additional regimen(s) subsequent to determination of platinum resistance; 4. Patients must have received one prior PARP inhibitor therapy, and there must be a = 6 month interval since treatment; 5. Female participants age 18-75 years; 6. Has measurable lesion per RECIST v1.1; 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 8. Life expectancy = 3 months; 9. Patients must have normal organ and bone marrow function; 10. Women of childbearing potential should have a negative serum or urine pregnancy test prior to receiving the first dose of study treatment; and should be willing to use one acceptable contraception (i.e., oral contraceptives, condoms, intrauterine devices [IUDs]) throughout the period of taking study treatment and for at least 6 months after the last dose of study drug(s). Exclusion Criteria: 1. Histological diagnosis of mucinous adenocarcinoma; 2. Has received prior therapy with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs); 3. Known or suspected allergy to any of study drugs; 4. Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York heart association [NYHA] class > 2, unstable angina, myocardial infarction, cardiac arrhythmia associated with hemodynamic instability (including corrected QT (QTc) interval = 450 ms in men, = 470 ms in female); 5. Has active ulcers, gastrointestinal perforation or obstruction; 6. Active bleeding or pathologic condition that carries a high risk of bleeding; 7. Inadequately controlled hypertension (systolic blood pressure = 150 mmHg and/or diastolic blood pressure = 90 mmHg) with or without treatment; 8. Major surgery within 28 days of starting study treatment; 9. Proteinuria = (++) or 24 hours total urine protein > 1.0 g; 10. Uncontrolled pericardial or pleural or peritoneal effusions; 11. Has a diagnosed and/or treated additional malignancy within the last 5 years. Exceptions include in situ cervical cancer, non-melanoma skin cancer, or superficial bladder tumors that has undergone potentially curative therapy; 12. Known Human Immunodeficiency Virus (HIV) infection; 13. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; 14. Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study. |
Country | Name | City | State |
---|---|---|---|
China | Sun Yat-sen University Cancer Cetntre | Guangzhou |
Lead Sponsor | Collaborator |
---|---|
Sun Yat-sen University | Hutchmed |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Biomarkers associated with the response to pamiparib combined with surufatinib | To identify the biomarkers, including but not limited to genomic, homologous recombination deficiency (HRD), that predict the efficacy of this study treatment. | from the first drug administration up to two years | |
Primary | Maximum tolerated dose (MTD) (Phase Ib) | MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a dose limiting toxicity (DLT) during the first cycles. DLT is defined as: grade 3 febrile neutropenia, grade 4 hematologic toxicities, and = grade 3 non-hematologic toxicities that occurred within the first cycle of treatment with pamiparib and surufatinib. | first 21 days of treatment | |
Primary | Recommended Phase 2 dose (RP2D) (Phase Ib) | Determine the RP2D of the pamiparib and surufatinib combination | first 21 days of treatment | |
Primary | Response Rate (ORR) (Phase II) | ORR is the proportion of patients with best response of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | from the first drug administration up to two years | |
Secondary | Progression-free Survival (PFS) | Time from the date of first study treatment administration to the date of first documented tumor progression or death due to any cause, whichever occurs first. | from the first drug administration up to two years | |
Secondary | Disease Control Rate (DCR) | Proportion of patients whose best overall response is either CR, PR, or SD. | from the first drug administration up to two years | |
Secondary | Duration of response (DOR) | Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first. | from the first drug administration up to two years | |
Secondary | Overall survival (OS) | Time from the date of first study treatment administration to the date of death due to any cause. | from the first drug administration up to 2 years | |
Secondary | Safety and tolerability | Incidence, nature, and severity of adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. | up to 90 days after last study treatment administration | |
Secondary | Patient Reported Outcomes (PROs) | Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire | from the first drug administration up to two years |
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