Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer
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 Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
Study Contact
- Name: Chunyan Lan, M.D.
- Phone Number: +862087343104
- Email: lanchy@sysucc.org.cn
Study Locations
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Guangzhou, China, 510060
- Sun Yat-sen University Cancer Cetntre
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: 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. |
Oral
Other Names:
Oral
Other Names:
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Recommended Phase 2 dose (RP2D) (Phase Ib)
Time Frame: first 21 days of treatment
|
Determine the RP2D of the pamiparib and surufatinib combination
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first 21 days of treatment
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The 6-month progression-free survival (PFS) rate (Phase II)
Time Frame: from the first drug administration up to two years
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The percentage of patients alive without documented progression 6 months after treatment initiation.
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from the first drug administration up to two years
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Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Duration of response (DOR)
Time Frame: from the first drug administration up to two years
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Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first.
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from the first drug administration up to two years
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Disease Control Rate (DCR)
Time Frame: from the first drug administration up to two years
|
Proportion of patients whose best overall response is either CR, PR, or SD.
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from the first drug administration up to two years
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Overall survival (OS)
Time Frame: from the first drug administration up to 2 years
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Time from the date of first study treatment administration to the date of death due to any cause.
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from the first drug administration up to 2 years
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Safety and tolerability
Time Frame: up to 90 days after last study treatment administration
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Incidence, nature, and severity of adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
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up to 90 days after last study treatment administration
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Patient Reported Outcomes (PROs)
Time Frame: from the first drug administration up to two years
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Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire
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from the first drug administration up to two years
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Objective response rate (ORR)
Time Frame: from the first drug administration up to two years
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The proportion of subjects with complete response (CR) or partial response (PR) according to RECIST 1.1
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from the first drug administration up to two years
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Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Biomarkers associated with the response to pamiparib combined with surufatinib
Time Frame: from the first drug administration up to two years
|
To identify the biomarkers, including but not limited to genomic, homologous recombination deficiency (HRD), that predict the efficacy of this study treatment.
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from the first drug administration up to two years
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Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Urogenital Diseases
- Genital Diseases
- Endocrine System Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Genital Diseases, Female
- Endocrine Gland Neoplasms
- Ovarian Diseases
- Adnexal Diseases
- Genital Neoplasms, Female
- Gonadal Disorders
- Ovarian Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Protein Kinase Inhibitors
- Heterocyclic Compounds
- Heterocyclic Compounds, 2-Ring
- Heterocyclic Compounds, Fused-Ring
- Nucleic Acids, Nucleotides, and Nucleosides
- Pharmacologic Actions
- Chemical Actions and Uses
- Carbohydrates
- Glycosides
- Purines
- Ribonucleotides
- Nucleotides
- Adenine Nucleotides
- Purine Nucleotides
- Polyribonucleotides
- Polynucleotides
- Adenosine Diphosphate Sugars
- Nucleoside Diphosphate Sugars
- Adenosine Diphosphate
- Tyrosine Kinase Inhibitors
- surufatinib
- pamiparib
- Poly A
- Adenosine Diphosphate Ribose
Other Study ID Numbers
Other Study ID Numbers
- B2022-348-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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