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A Study of Adavosertib (MK-1775) in Combination With Topotecan/Cisplatin in Participants With Cervical Cancer (MK-1775-008)

Primary Purpose

Cervical Cancer

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
adavosertib
Topotecan
Cisplatin
Placebo to adavosertib
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Part 1: adavosertib + topotecan/cisplatin

    Part 2: adavosertib + topotecan/cisplatin

    Part 2: Placebo to adavosertib + topotecan/cisplatin

    Arm Description

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR)
    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.
    Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
    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.
    Part 2: Length of Time for Progression-free Survival (PFS)
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    February 24, 2010
    Last Updated
    August 31, 2023
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01076400
    Brief Title
    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

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Terminated
    Why Stopped
    The sponsor permanently suspended new enrollment into the trial and discontinued the study; which was not related to any concerns over product safety.
    Study Start Date
    May 31, 2010 (Actual)
    Primary Completion Date
    June 13, 2011 (Actual)
    Study Completion Date
    June 13, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cervical Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    7 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Part 1: adavosertib + topotecan/cisplatin
    Arm Type
    Experimental
    Arm Description
    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 Title
    Part 2: adavosertib + topotecan/cisplatin
    Arm Type
    Experimental
    Arm Description
    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 Title
    Part 2: Placebo to adavosertib + topotecan/cisplatin
    Arm Type
    Placebo Comparator
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    adavosertib
    Other Intervention Name(s)
    MK-1775
    Intervention Description
    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 Type
    Drug
    Intervention Name(s)
    Topotecan
    Intervention Description
    Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Intervention Description
    Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to adavosertib
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Part 1: Percentage of Participants Whose Best Confirmed Response is Partial Response (PR) or Complete Response (CR)
    Description
    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.
    Time Frame
    Up to approximately 1 year
    Title
    Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
    Description
    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.
    Time Frame
    Up to approximately 1 year
    Title
    Part 2: Length of Time for Progression-free Survival (PFS)
    Description
    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.
    Time Frame
    Up to approximately 1 year

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Links:
    URL
    https://www.merckclinicaltrials.com/
    Description
    Merck Clinical Trial Information

    Learn more about this trial

    A Study of Adavosertib (MK-1775) in Combination With Topotecan/Cisplatin in Participants With Cervical Cancer (MK-1775-008)

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