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

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ClinicalTrials.gov Identifier: NCT01076400
Recruitment Status : Terminated (The sponsor permanently suspended new enrollment into the trial and discontinued the study; which was not related to any concerns over product safety.)
First Posted : February 26, 2010
Results First Posted : December 14, 2017
Last Update Posted : July 20, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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Brief Summary:
This study will be conducted in two parts. Part 1 will determine whether administration of MK1775 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 MK1775 with topotecan and cisplatin. Part 2 of the study will evaluate whether treatment with MK1775 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 MK-1775, 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.

Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: MK-1775 Drug: Topotecan Drug: Cisplatin Drug: Placebo to MK-1775 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Two Part, Phase I-IIa Study Evaluating MK1775 in Combination With Topotecan/Cisplatin in Adult Patients With Cervical Cancer
Actual Study Start Date : May 31, 2010
Actual Primary Completion Date : June 13, 2011
Actual Study Completion Date : June 13, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: MK-1775 + topotecan/cisplatin
Part 1: Dose escalation study. MK-1775 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.
 Drug: MK-1775
MK-1775 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.

Drug: Topotecan
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.

Drug: Cisplatin
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1.
Experimental: Part 2: MK-1775 + topotecan/cisplatin
Part 2: MK-1775 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.
 Drug: MK-1775
MK-1775 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.

Drug: Topotecan
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.

Drug: Cisplatin
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1.
Placebo Comparator: Part 2: Placebo to MK-1775 + topotecan/cisplatin
Part 2: Placebo to MK-1775 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.
 Drug: Topotecan
Topotecan is administered at a dosage of 0.75 mg/m^2 by intravenous (IV) infusion over 30 minutes on Days 1-3.

Drug: Cisplatin
Cisplatin is administered at a dosage of 50 mg/m^2 by IV infusion over 30 minutes on Day 1.

Drug: Placebo to MK-1775
Placebo to MK-1775 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01076400


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01076400     History of Changes
Other Study ID Numbers: 1775-008
2009-017054-12 ( EudraCT Number )
MK-1775-008 ( Other Identifier: Merck Protocol Number )
First Posted: February 26, 2010    Key Record Dates
Results First Posted: December 14, 2017
Last Update Posted: July 20, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
 Cisplatin
Topotecan
MK-1775
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action