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NCT04516447PHASE1Recruiting

A Study of Azenosertib (ZN-c3) in Patients With Ovarian Cancer

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Start Date

10/26/2020

Completion Date

6/30/2028

Summary

This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of azenosertib (ZN-c3) in combination with other drugs.

Detailed Description

This is a Phase 1b open-label, multicenter study evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of azenosertib (also known as ZN-c3) in combination with chemotherapy or bevacizumab. This study consists of 2 parts: Part 1 (completed and no longer recruiting): Azenosertib in combination with chemotherapy Azenosertib was assessed in combination with chemotherapy in subjects with platinum-resistant advanced ovarian, peritoneal, or fallopian tube cancer. Part 2: Azenosertib in combination with bevacizumab * Dose Escalation (completed and no longer recruiting): Azenosertib was assessed in combination with bevacizumab as first-line (1L) or second-line (2L) maintenance therapy in subjects with advanced ovarian, peritoneal, or fallopian tube cancer after platinum-based chemotherapy to determine a recommended dose for expansion. * Dose Expansion: Azenosertib will be assessed in combination with bevacizumab as 2L maintenance therapy in subjects with advanced ovarian, peritoneal, or fallopian tube cancer after platinum-based chemotherapy.

Eligibility Criteria

Age Range: 18 years to No maximum

INCLUSION CRITERIA: For Part 1: * Histologically or cytologically confirmed FIGO Stage III/IV high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal carcinoma. * Subjects must have received 1 or 2 prior therapeutic regimens/lines of therapy in the advanced or metastatic setting. At least one regimen must have contained cisplatin or carboplatin. * The disease must be platinum resistant (ie, the PFI must have been \< 6 months). Platinum refractory disease (ie, PD during first-line platinum-based therapy) is allowed. For Part 2 Dose Escalation: Prior therapy: • Subjects must have received 6 cycles of platinum-based doublet chemotherapy in the 1L or 2L setting as their most recent therapy Response to prior platinum therapy: 1. In the 1L setting: Complete Response, Partial Response, or Stable Disease to platinum-based chemotherapy. 2. In the 2L setting: 1. Progressive Disease \>183 days after receiving the last dose of platinum chemotherapy in the 1L setting, 2. Complete Response, Partial Response, or Stable Disease to 2L platinum-based chemotherapy. * Adequate hematologic, and organ function For Part 2 Dose Expansion: * Subjects must have at least 4 cycles of platinum-based chemotherapy in 2L and have Complete Response, Partial Response, or Stable Disease * Subjects must have progressed while on a PARP inhibitor for 1L maintenance Additional protocol-defined inclusion criteria may apply EXCLUSION CRITERIA: * Histology of abdominal adenocarcinoma of unknown origin or diagnosis of a borderline ovarian tumor. * Subjects with carcinosarcomas (even if there is a serous component) * A serious illness or medical condition(s) * Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy. Additional protocol-defined exclusion criteria may apply

Interventions

DRUG

Azenosertib

DRUG

Carboplatin

DRUG

Pegylated liposomal doxorubicin

DRUG

Paclitaxel

DRUG

Gemcitabine

BIOLOGICAL

Bevacizumab

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Conditions

Solid TumorEpithelial Ovarian CancerFallopian Tube CancerPeritoneal Cancer

Locations

Site 0264

Aurora, Colorado 80045

United States

Site 0104

Boston, Massachusetts 02215

United States

Site 0111

St Louis, Missouri 53110

United States

Site 0173

New York, New York 10029

United States

Site 0259

Durham, North Carolina 27710

United States

Site 0191

Providence, Rhode Island 02905

United States

Site 0196

Nashville, Tennessee 37203

United States

Site 0103

Houston, Texas 77030

United States

Site 2707

South Brisbane, Queensland 4101

Australia

Site 2708

Sunshine Coast, Queensland 4556

Australia

Site 2709

Adelaide, South Australia 5000

Australia

Site 2716

Melbourne, Victoria 3121

Australia

Site 2706

Melbourne, Victoria 3144

Australia

Site 2705

Nedlands, Western Australia 6009

Australia

Site 1001

Banja Luka, 78000

Bosnia and Herzegovina

Site 1002

Sarajevo, 71000

Bosnia and Herzegovina

Site 1003

Tuzla, 75000

Bosnia and Herzegovina

Site 1202

Panagyurishte, 4500

Bulgaria

Site 1201

Sofia, 1632

Bulgaria

Site 1401

Tbilisi, 0112

Georgia

Site 1902

Belgrade, 11080

Serbia

Site 2901

Busan,

South Korea

Site 2903

Seoul, 03080

South Korea

Site 2904

Seoul, 05505

South Korea