Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer

NCT ID: NCT05494580

Last Updated: 2023-04-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-22
• Study Completion Date: 2025-08-10

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.

Conditions

Ovarian Cancer; Ovarian Carcinoma; Platinum-resistant Ovarian Cancer; Fallopian Tube Carcinosarcoma; Primary Peritoneal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pamiparib + Surufatinib (Phase Ib/II)

Phase Ib:

A dose de-escalation schedule is used in the phase Ib dose finding part. Dose Level 1 (starting dose): pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 250 mg administered orally once daily on a 21-day treatment cycle. If ≥2/6 patients experience a dose limiting toxicity (DLT), we will de-escalate to Dose Level 2: pamiparib 40 mg administered orally twice daily (fixed dose) and surufatinib 200 mg administered orally once daily on a 21-day treatment cycle. Approximately 3-12 patients will be enrolled in phase Ib study.

Phase II:

The phase II part will begin once the recommended phase 2 dose (RP2D) of surufatinib have been determined in the Phase Ib in order to assess antitumor activity of pamiparib and surufatinib combination. In phase II study, pamiparib 40 mg orally twice daily and surufatinib PR2D will be administered.

Group Type: EXPERIMENTAL

Pamiparib

Intervention Type: DRUG

Oral

Surufatinib

Intervention Type: DRUG

Oral

Interventions

Pamiparib

Oral

Intervention Type: DRUG

Surufatinib

Oral

Intervention Type: DRUG

Other Intervention Names

Poly (ADP-ribose) polymerase (PARP) inhibitor; Tyrosine Kinase Inhibitor

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hutchmed

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Xin Huang

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Cetntre

Guangzhou, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Chunyan Lan, M.D.

Role: CONTACT

lanchy@sysucc.org.cn

+862087343104

Facility Contacts

Chunyan Lan

Role: primary

lanchy@sysucc.org.cn

+862087343104

Other Identifiers

B2022-348-01

Identifier Type: -

Identifier Source: org_study_id