Conditions: Cervical Cancer
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 7
Healthy volunteers: no

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.

Detailed description:

Arms:
arm 1: Part 1: Dose escalation study. adavosertib capsules will be administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m\^2 by intravenous (IV) infusion over 30 minutes on Days 1-3 . Cisplatin will be administered at a dosage of 50 mg/m\^2 by IV infusion over 30 minutes on Day 1. arm 2: Part 2: adavosertib capsules will be administered at the dose determined in Part 1 twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m\^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m\^2 by IV infusion over 30 minutes on Day 1. arm 3: Part 2: Placebo to adavosertib capsules will be administered twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. Topotecan will be administered at a dosage of 0.75 mg/m\^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. Cisplatin will be administered at a dosage of 50 mg/m\^2 by IV infusion over 30 minutes on Day 1.

Interventions: intervention 1: adavosertib intervention 2: Topotecan intervention 3: Cisplatin intervention 4: Placebo to adavosertib
Intervention descriptions: intervention 1: Adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle. intervention 2: Topotecan is administered at a dosage of 0.75 mg/m\^2 by intravenous (IV) infusion over 30 minutes on Days 1-3. intervention 3: Cisplatin is administered at a dosage of 50 mg/m\^2 by IV infusion over 30 minutes on Day 1. intervention 4: Placebo to adavosertib capsules are administered in sequentially rising dose levels twice daily for a total of nine doses on Days 1-5 of a 21-day cycle.

Protocol document: