Fallopian Tube Carcinosarcoma, Ovarian Cancer, Ovarian Carcinoma, Platinum-resistant Ovarian Cancer, Primary Peritoneal Cancer
Conditions
Keywords
Ovarian cancer, PARP inhibitor, Antiangiogenic agents, Platinum-resistant
Brief summary
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.
Interventions
DRUGPamiparib
Oral
DRUGSurufatinib
Oral
Sponsors
Sun Yat-sen University
Hutchmed
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Drug: Pamiparib Drug: Surufatinib
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The 6-month progression-free survival (PFS) rate (Phase II) | from the first drug administration up to two years | The percentage of patients alive without documented progression 6 months after treatment initiation. |
| Recommended Phase 2 dose (RP2D) (Phase Ib) | first 21 days of treatment | Determine the RP2D of the pamiparib and surufatinib combination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | from the first drug administration up to 2 years | Time from the date of first study treatment administration to the date of death due to any cause. |
| Objective response rate (ORR) | from the first drug administration up to two years | The proportion of subjects with complete response (CR) or partial response (PR) according to RECIST 1.1 |
| Safety and tolerability | up to 90 days after last study treatment administration | Incidence, nature, and severity of adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| Disease Control Rate (DCR) | from the first drug administration up to two years | Proportion of patients whose best overall response is either CR, PR, or SD. |
| Patient Reported Outcomes (PROs) | from the first drug administration up to two years | Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire |
| Duration of response (DOR) | from the first drug administration up to two years | Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first. |
Countries
China
Outcome results
None listed