A Study of Adavosertib (MK-1775) in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004)

NCT ID: NCT01357161

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-26
• Study Completion Date: 2016-08-08

Brief Summary

This is a study of the safety and efficacy of adavosertib in combination with paclitaxel plus carboplatin in the treatment of ovarian, fallopian tube, and primary peritoneal tumors with the P53 mutation. In Part 1, a small group of participants will receive adavosertib along with paclitaxel plus carboplatin to establish the tolerability of adavosertib with this combination. In Part 2, participants will be randomly assigned to receive either adavosertib plus paclitaxel and carboplatin OR placebo plus paclitaxel and carboplatin to assess efficacy of adavosertib compared to placebo. The primary hypothesis of the study (Part 2) is that administration of adavosertib in combination with paclitaxel plus carboplatin in participants with platinum sensitive p53 mutant ovarian cancer will result in improvement in progression free survival (PFS) per enhanced Response Evaluation Criteria In Solid Tumors version 1.1 (enhanced RECIST 1.1) compared to participants treated with paclitaxel plus carboplatin alone.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: adavosertib 225 mg + paclitaxel +carboplatin

During the open-label run-in, participants receive 225 mg adavosertib twice daily (BID) starting on Day 1 of Cycle 1 (cycle=21 days) for a total of 5 doses. Participants receive adavosertib in combination with paclitaxel (175 mg/m2) and carboplatin (area under the curve \[AUC\] 5).

Group Type: EXPERIMENTAL

adavosertib

Intervention Type: DRUG

Adavosertib capsules, orally, twice a day (BID) for a total of 5 doses starting on Day 1 of each 3-week cycle

paclitaxel

Intervention Type: DRUG

paclitaxel, intravenous (IV) infusion on Day 1 of each 3-week cycle

carboplatin

Intervention Type: DRUG

carboplatin, IV infusion on Day 1 of each 3-week cycle

Part 2: adavosertib 225 mg + paclitaxel +carboplatin

During Part 2, participants receive 225 mg adavosertib BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants receive adavosertib in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 5).

Group Type: EXPERIMENTAL

adavosertib

Intervention Type: DRUG

Adavosertib capsules, orally, twice a day (BID) for a total of 5 doses starting on Day 1 of each 3-week cycle

paclitaxel

Intervention Type: DRUG

paclitaxel, intravenous (IV) infusion on Day 1 of each 3-week cycle

carboplatin

Intervention Type: DRUG

carboplatin, IV infusion on Day 1 of each 3-week cycle

Part 2: Placebo + paclitaxel +carboplatin

During Part 2, participants receive matched placebo to adavosertib BID starting on Day 1 of each 21 day cycle for a total of 5 doses. Participants receive placebo in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 5).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo to adavosertib, capsule, orally, BID for a total of 5 doses, starting on Day 1 of each 3-week cycle

paclitaxel

Intervention Type: DRUG

paclitaxel, intravenous (IV) infusion on Day 1 of each 3-week cycle

carboplatin

Intervention Type: DRUG

carboplatin, IV infusion on Day 1 of each 3-week cycle

Interventions

adavosertib

Adavosertib capsules, orally, twice a day (BID) for a total of 5 doses starting on Day 1 of each 3-week cycle

Intervention Type: DRUG

Placebo

placebo to adavosertib, capsule, orally, BID for a total of 5 doses, starting on Day 1 of each 3-week cycle

Intervention Type: DRUG

paclitaxel

paclitaxel, intravenous (IV) infusion on Day 1 of each 3-week cycle

Intervention Type: DRUG

carboplatin

carboplatin, IV infusion on Day 1 of each 3-week cycle

Intervention Type: DRUG

Other Intervention Names

MK-1775; Taxol; paraplatin

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed non-low grade, non-borderline (low malignant potential) ovarian, fallopian tube, or primary peritoneal cancer which has progressed after paclitaxel / platinum-based therapy.
• Platinum-sensitive disease. Radiological progression must have occurred 6 months or more after the completion of the most recent platinum-based treatment.
• Measurable disease.
• Available tumor sample(s).
• Performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Adequate organ function.

Exclusion Criteria

• Pregnancy or the intention to become pregnant during the course of the study.
• Participation in a study with an investigational compound or device within 28 days of receiving first dose of study medication.
• Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Primary CNS tumor.
• Known hypersensitivity or contraindications to the components of potential study therapy (paclitaxel, carboplatin, adavosertib) or its analogs (i.e., cremophor, mannitol, etc.).
• Participant requires the use of medications or products that are metabolized by, or inhibit, or induce Cytochrome P450 3A (CYP3A4).
• Ongoing peripheral neuropathies ≥Grade 2 and related to previous treatment.
• Known psychiatric or substance abuse disorders.
• Regular use (including "recreational use") of any illicit drugs or recent history (within the last year) of drug or alcohol abuse.
• HIV positive.
• Active Hepatitis B or C.
• Symptomatic ascites or pleural effusion.
• Clinical history suggestive of Li Fraumeni Syndrome.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Related Links

https://www.merckclinicaltrials.com/

Merck Clinical Trials Information

Other Identifiers

2011-002803-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1775-004

Identifier Type: -

Identifier Source: org_study_id