- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01076400
A Study of Adavosertib (MK-1775) in Combination With Topotecan/Cisplatin in Participants With Cervical Cancer (MK-1775-008)
August 31, 2023 updated by: Merck Sharp & Dohme LLC
A Two Part, Phase I-IIa Study Evaluating MK1775 in Combination With Topotecan/Cisplatin in Adult Patients With Cervical Cancer
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
7
Phase
- Phase 2
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1: adavosertib + topotecan/cisplatin
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.
|
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 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.
Other Names:
|
Experimental: Part 2: adavosertib + topotecan/cisplatin
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.
|
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 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.
Other Names:
|
Placebo Comparator: Part 2: Placebo to adavosertib + topotecan/cisplatin
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.
|
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR)
Time Frame: Up to approximately 1 year
|
On the basis of Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, PR is at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters.
CR is the disappearance of all extranodal target lesions, where all pathological lymph nodes must have decreased to <10 mm in the short axis.
|
Up to approximately 1 year
|
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Up to approximately 1 year
|
A DLT is a protocol-defined, (hematologic and non-hematologic), AE that must be definitely, probably, or possibly related to the study therapy.
A DLT is any of the following: Grade 4-5 hematological toxicity; Grade 3 or Grade 4 neutropenia with fever >38.°C and/or infection requiring antibiotic or anti-fungal treatment.
Non-hematologic dose-limiting toxicities are any Grade 3, 4, or 5 non-hematologic toxicity, with specific exceptions.
If occurring within the first cycle of combination therapy: unresolved drug-related toxicity, preventing (re) treatment for 3 weeks or more from the date of the next scheduled treatment or any drug-related toxicity preventing the participant from taking at least 75% of the doses of MK-1775 with each administration of chemotherapy.
|
Up to approximately 1 year
|
Part 2: Length of Time for Progression-free Survival (PFS)
Time Frame: Up to approximately 1 year
|
PFS is the length of time during and after treatment that a participant lives, but whose tumor progression does not worsen.
PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier.
Tumor volume changes of +20% for progressive disease was used to be consistent with RECIST 1.1.
|
Up to approximately 1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 31, 2010
Primary Completion (Actual)
June 13, 2011
Study Completion (Actual)
June 13, 2011
Study Registration Dates
First Submitted
February 24, 2010
First Submitted That Met QC Criteria
February 24, 2010
First Posted (Estimated)
February 26, 2010
Study Record Updates
Last Update Posted (Actual)
September 18, 2023
Last Update Submitted That Met QC Criteria
August 31, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Uterine Cervical Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Topotecan
- Adavosertib
Other Study ID Numbers
- 1775-008
- 2009-017054-12 (EudraCT Number)
- MK-1775-008 (Other Identifier: Merck Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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University of California, San DiegoWithdrawnCervical Cancer | Cervical Cancer Stage | Cervical Cancer Stage IB2 | Cervical Cancer Stage IB1 | Cervical Cancer Stage I | Cervical Cancer Stage IB | Cervical Cancer Stage II | Cervical Cancer Stage IIa | Cervical Cancer, Stage IIB | Cervical Cancer, Stage III | Cervical Cancer Stage IIIB | Cervical Cancer... and other conditionsUnited States
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