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Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer

Primary Purpose

Ovarian Cancer, Ovarian Carcinoma, Platinum-resistant Ovarian Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Pamiparib
Surufatinib
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian cancer, PARP inhibitor, Antiangiogenic agents, Platinum-resistant

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Sun Yat-sen University Cancer CetntreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pamiparib + Surufatinib (Phase Ib/II)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
Recommended Phase 2 dose (RP2D) (Phase Ib)
Determine the RP2D of the pamiparib and surufatinib combination
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.

Secondary Outcome Measures

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.
Disease Control Rate (DCR)
Proportion of patients whose best overall response is either CR, PR, or SD.
Duration of response (DOR)
Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
Overall survival (OS)
Time from the date of first study treatment administration to the date of death due to any cause.
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.
Patient Reported Outcomes (PROs)
Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire

Full Information

First Posted
July 26, 2022
Last Updated
April 8, 2023
Sponsor
Sun Yat-sen University
Collaborators
Hutchmed
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1. Study Identification

Unique Protocol Identification Number
NCT05494580
Brief Title
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 22, 2022 (Actual)
Primary Completion Date
August 10, 2024 (Anticipated)
Study Completion Date
August 10, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
Collaborators
Hutchmed

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Ovarian Carcinoma, Platinum-resistant Ovarian Cancer, Fallopian Tube Carcinosarcoma, Primary Peritoneal Cancer
Keywords
Ovarian cancer, PARP inhibitor, Antiangiogenic agents, Platinum-resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Drug: Pamiparib Drug: Surufatinib
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pamiparib + Surufatinib (Phase Ib/II)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pamiparib
Other Intervention Name(s)
Poly (ADP-ribose) polymerase (PARP) inhibitor
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Surufatinib
Other Intervention Name(s)
Tyrosine Kinase Inhibitor
Intervention Description
Oral
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) (Phase Ib)
Description
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.
Time Frame
first 21 days of treatment
Title
Recommended Phase 2 dose (RP2D) (Phase Ib)
Description
Determine the RP2D of the pamiparib and surufatinib combination
Time Frame
first 21 days of treatment
Title
Response Rate (ORR) (Phase II)
Description
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.
Time Frame
from the first drug administration up to two years
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
from the first drug administration up to two years
Title
Disease Control Rate (DCR)
Description
Proportion of patients whose best overall response is either CR, PR, or SD.
Time Frame
from the first drug administration up to two years
Title
Duration of response (DOR)
Description
Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
Time Frame
from the first drug administration up to two years
Title
Overall survival (OS)
Description
Time from the date of first study treatment administration to the date of death due to any cause.
Time Frame
from the first drug administration up to 2 years
Title
Safety and tolerability
Description
Incidence, nature, and severity of adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time Frame
up to 90 days after last study treatment administration
Title
Patient Reported Outcomes (PROs)
Description
Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire
Time Frame
from the first drug administration up to two years
Other Pre-specified Outcome Measures:
Title
Biomarkers associated with the response to pamiparib combined with surufatinib
Description
To identify the biomarkers, including but not limited to genomic, homologous recombination deficiency (HRD), that predict the efficacy of this study treatment.
Time Frame
from the first drug administration up to two years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed Informed Consent Form; Histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; 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; Patients must have received one prior PARP inhibitor therapy, and there must be a ≥ 6 month interval since treatment; Female participants age 18-75 years; Has measurable lesion per RECIST v1.1; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Life expectancy ≥ 3 months; Patients must have normal organ and bone marrow function; 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: Histological diagnosis of mucinous adenocarcinoma; Has received prior therapy with small molecule antiangiogenic receptor tyrosine kinase inhibitors (TKIs); Known or suspected allergy to any of study drugs; 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); Has active ulcers, gastrointestinal perforation or obstruction; Active bleeding or pathologic condition that carries a high risk of bleeding; Inadequately controlled hypertension (systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg) with or without treatment; Major surgery within 28 days of starting study treatment; Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g; Uncontrolled pericardial or pleural or peritoneal effusions; 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; Known Human Immunodeficiency Virus (HIV) infection; Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chunyan Lan, M.D.
Phone
+862087343104
Email
lanchy@sysucc.org.cn
Facility Information:
Facility Name
Sun Yat-sen University Cancer Cetntre
City
Guangzhou
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunyan Lan
Phone
+862087343104
Email
lanchy@sysucc.org.cn
First Name & Middle Initial & Last Name & Degree
Chunyan Lan

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer

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