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Pamiparib Plus Surufatinib in Patients With Platinum-resistant Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05494580
Recruitment Status : Not yet recruiting
First Posted : August 10, 2022
Last Update Posted : August 10, 2022
Sponsor:
Collaborator:
Hutchmed
Information provided by (Responsible Party):
Xin Huang, Sun Yat-sen University

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Ovarian Carcinoma Platinum-resistant Ovarian Cancer Fallopian Tube Carcinosarcoma Primary Peritoneal Cancer Drug: Pamiparib Drug: Surufatinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Drug: Pamiparib Drug: Surufatinib
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : August 10, 2022
Estimated Primary Completion Date : August 10, 2024
Estimated Study Completion Date : August 10, 2025


Arm Intervention/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.

Drug: Pamiparib
Oral
Other Name: Poly (ADP-ribose) polymerase (PARP) inhibitor

Drug: Surufatinib
Oral
Other Name: Tyrosine Kinase Inhibitor




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) (Phase Ib) [ Time Frame: first 21 days of treatment ]
    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.

  2. Recommended Phase 2 dose (RP2D) (Phase Ib) [ Time Frame: first 21 days of treatment ]
    Determine the RP2D of the pamiparib and surufatinib combination

  3. Response Rate (ORR) (Phase II) [ Time Frame: from the first drug administration up to two years ]
    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 :
  1. Progression-free Survival (PFS) [ Time Frame: from the first drug administration up to two years ]
    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.

  2. 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.

  3. Duration of response (DOR) [ Time Frame: 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.

  4. Overall survival (OS) [ Time Frame: 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.

  5. Safety and tolerability [ Time Frame: 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.

  6. Patient Reported Outcomes (PROs) [ Time Frame: 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


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05494580


Contacts
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Contact: Chunyan Lan, M.D. 18928806306 lanchy@sysucc.org.cn

Sponsors and Collaborators
Sun Yat-sen University
Hutchmed
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Responsible Party: Xin Huang, Prof., Sun Yat-sen University
ClinicalTrials.gov Identifier: NCT05494580    
Other Study ID Numbers: B2022-348-01
First Posted: August 10, 2022    Key Record Dates
Last Update Posted: August 10, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Xin Huang, Sun Yat-sen University:
Ovarian cancer
PARP inhibitor
Antiangiogenic agents
Platinum-resistant
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinosarcoma
Mixed Tumor, Mullerian
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Complex and Mixed
Sarcoma
Neoplasms, Connective and Soft Tissue
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents