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| Name | Class |
|---|---|
| Hutchmed | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pamiparib + Surufatinib (Phase Ib/II) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pamiparib | Drug | Oral |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Recommended Phase 2 dose (RP2D) (Phase Ib) | Determine the RP2D of the pamiparib and surufatinib combination | first 21 days of treatment |
| The 6-month progression-free survival (PFS) rate (Phase II) | The percentage of patients alive without documented progression 6 months after treatment initiation. | from the first drug administration up to two years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response rate (ORR) | The proportion of subjects with complete response (CR) or partial response (PR) according to RECIST 1.1 | from the first drug administration up to two years |
| Disease Control Rate (DCR) |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers associated with the response to pamiparib combined with surufatinib | To identify the biomarkers, including but not limited to genomic, homologous recombination deficiency (HRD), that predict the efficacy of this study treatment. | from the first drug administration up to two years |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-sen University Cancer Cetntre | Guangzhou | 510060 | China |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
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| ID | Term |
|---|---|
| C000707927 | pamiparib |
| D011061 | Poly A |
| D000246 | Adenosine Diphosphate Ribose |
| C000717729 | surufatinib |
| D000092004 | Tyrosine Kinase Inhibitors |
| ID | Term |
|---|---|
| D011131 | Polyribonucleotides |
| D011119 | Polynucleotides |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
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Drug: Pamiparib Drug: Surufatinib
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| Surufatinib | Drug | Oral |
|
|
Proportion of patients whose best overall response is either CR, PR, or SD.
| from the first drug administration up to two years |
| Duration of response (DOR) | Time from first documented response (CR or PR) until documented disease progression or death, whichever occurs first. | from the first drug administration up to two years |
| Overall survival (OS) | Time from the date of first study treatment administration to the date of death due to any cause. | from the first drug administration up to 2 years |
| 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. | up to 90 days after last study treatment administration |
| Patient Reported Outcomes (PROs) | Determination of changes in PROs with Functional Assessment of Cancer Therapy for patients with ovarian cancer (FACT-O) questionnaire | from the first drug administration up to two years |
| D000291 |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D000247 | Adenosine Diphosphate Sugars |
| D000244 | Adenosine Diphosphate |
| D000227 | Adenine Nucleotides |
| D011685 | Purine Nucleotides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009702 | Nucleoside Diphosphate Sugars |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D012265 | Ribonucleotides |
| D047428 | Protein Kinase Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |