Clinical trial NCT05494580: Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Ovarian Carcinoma
Platinum-resistant Ovarian Cancer
Fallopian Tube Carcinosarcoma
Primary Peritoneal Cancer
Keywords: Ovarian cancer
PARP inhibitor
Antiangiogenic agents
Platinum-resistant
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Hutchmed
First posted: 2022-08-10
Enrollment: 38
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Drug: Pamiparib Drug: Surufatinib
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) (Phase Ib)
timeFrame: first 21 days of treatment
measure: Recommended Phase 2 dose (RP2D) (Phase Ib)
timeFrame: first 21 days of treatment
measure: Response Rate (ORR) (Phase II)
timeFrame: from the first drug administration up to two years
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: from the first drug administration up to two years
measure: Disease Control Rate (DCR)
timeFrame: from the first drug administration up to two years
measure: Duration of response (DOR)
timeFrame: from the first drug administration up to two years
measure: Overall survival (OS)
timeFrame: from the first drug administration up to 2 years
measure: Safety and tolerability
timeFrame: up to 90 days after last study treatment administration
measure: Patient Reported Outcomes (PROs)
timeFrame: from the first drug administration up to two years
Other outcomes:
measure: Biomarkers associated with the response to pamiparib combined with surufatinib
timeFrame: from the first drug administration up to two years
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Cetntre
Study officials:
References: