Clinical trial NCT01357161: 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)
Official title: A Randomized, Phase II Study Evaluating MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Adult Patients With Platinum Sensitive p53 Mutant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-05-20
Enrollment: 136
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part 2: Median Progression-free Survival (PFS) in Weeks Based on Enhanced Response Evaluation Criteria In Solid Tumors Version 1.1 (Enhanced RECIST 1.1) by Independent Radiology Review
timeFrame: Up to 57 months
measure: Part 1: Number of Participants With a Dose Limiting Toxicity (DLT)
timeFrame: During Cycle 1 of Part 1 (first 21 days)
measure: Parts 1 and 2: Percentage of Participants That Experienced an Adverse Event (AE)
timeFrame: Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)
measure: Parts 1 and 2: Percentage of Participants That Discontinued Study Treatment Due to an AE
timeFrame: Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)
Secondary outcomes:
measure: Part 1: Objective Response Rate (ORR) Per Gynecological Cancer Intergroup (GCIG) Criteria Based on Both RECIST 1.1 and Cancer Antigen 125 (CA-125) Level by Independent Radiology Review
timeFrame: Up to 57 months
measure: Part 2: Median PFS in Weeks Based on RECIST 1.1 by Independent Radiology Review
timeFrame: Up to 57 months
measure: Part 2: ORR Per GCIG Criteria Based on Both Enhanced RECIST 1.1 and CA125 Level by Independent Radiology Review
timeFrame: Up to 57 months
measure: Part 2: Median Overall Survival (OS) in Months
timeFrame: Up to 57 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: