Clinical trial NCT01076400: A Study of Adavosertib (MK-1775) in Combination With Topotecan/Cisplatin in Participants With Cervical Cancer (MK-1775-008)
Official title: A Two Part, Phase I-IIa Study Evaluating MK1775 in Combination With Topotecan/Cisplatin in Adult Patients With Cervical Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-02-26
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will be conducted in two parts. Part 1 will determine whether administration of adavosertib in combination with topotecan and cisplatin is generally well-tolerated and causes clinical objective responses in patients with cervical cancer. Part 1 will also define the recommended Phase 2 dose and maximum tolerated dose (MTD) of the combination of adavosertib with topotecan and cisplatin. Part 2 of the study will evaluate whether treatment with adavosertib in combination with topotecan and cisplatin causes an improvement in progression-free survival (PFS) compared to treatment with topotecan and cisplatin alone and will further evaluate the tolerability of the combination treatment. The primary hypothesis is the combination of adavosertib, topotecan and cisplatin causes objective radiological responses (assessed per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) in ≥30% of participants. Due to the early termination of the study by the sponsor, no participants were enrolled in Part 2 of the study.


Eligibility criteria: Inclusion Criteria:

* Has advanced, metastatic, and recurrent squamous cell, adenosquamous, or adeno-carcinoma of the uterine cervix (Stage II - IVb)
* Has received cisplatin in combination with radiation as initial or adjuvant treatment for their cervical cancer
* Has not received any other treatment for their cancer following the cisplatin-based chemo-radiation or targeted therapy except non-cytotoxic targeted therapy
* Recurrence must be at least 6 months post cisplatin-based chemotherapy
* Has measurable disease
* Performance status on the Eastern Cooperative Oncology Group (ECOG) Performance Scale is less than or equal to 1
* Has a negative pregnancy test within 72 hours of the first dose of study medication

Exclusion Criteria:

* Has had chemotherapy, radiotherapy, or biological therapy within 6 months of entering the study
* Has a history of vascular thrombotic events or vascular reconstruction
* Has active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has a primary CNS tumor
* Requires the use of medications or products that are metabolized by, or inhibit or induce CYP3A4 (Cytochrome P450 3A4)
* Is expecting to reproduce within the duration of the study or is pregnant or breastfeeding
* Is known to be Human Immunodeficiency Virus (HIV)-positive
* Has known active Hepatitis B or C
* Has a known history of interstitial lung disease or pulmonary fibrosis
* Has symptomatic ascites or pleural effusion
* Has a clinical history suggestive of Li-Fraumeni Syndrome

Primary outcomes:
measure: Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR)
timeFrame: Up to approximately 1 year
measure: Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to approximately 1 year
measure: Part 2: Length of Time for Progression-free Survival (PFS)
timeFrame: Up to approximately 1 year
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: