A Study of MK1775 in Combination With Topotecan/Cisplatin in Patients With Cervical Cancer (1775-008)

This study has been terminated.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01076400
First received: February 24, 2010
Last updated: June 22, 2011
Last verified: June 2011
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Drug: MK1775 + topotecan + cisplatin
Drug: Comparator: MK1775 + topotecan + cisplatin
Drug: Comparator: Placebo to MK1775 + topotecan + cisplatin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Part 1: Objective response rate [ Time Frame: Treatment response will be measured every two cycles (1 cycle = 21 days) ] [ Designated as safety issue: No ]
  • Part 1: Maximum tolerated dose as determined by the number of dose limiting toxicities (DLTs) per dose level [ Time Frame: End of Cycle 1 (1 Cycle = 21 Days) ] [ Designated as safety issue: Yes ]
  • Part 2: Progression-free survival [ Time Frame: Tumor progression will be assessed every two cycles (1 Cycle = 21 Days) ] [ Designated as safety issue: No ]

Enrollment: 7
Study Start Date: May 2010
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1
Part 1: MK1775 + topotecan + cisplatin dose escalation
Drug: MK1775 + topotecan + cisplatin
Part 1: Dose escalation study. MK1775 capsules 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.
Experimental: Part 2, Arm 1
Part 2, Arm 1: MK1775 + topotecan + cisplatin
Drug: Comparator: MK1775 + topotecan + cisplatin
Part 2, Arm 1: MK1775 capsules 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.
Active Comparator: Part 2, Arm 2
Part 2, Arm 2: Placebo to MK1775 + topotecan + cisplatin
Drug: Comparator: Placebo to MK1775 + topotecan + cisplatin
Part 2, Arm 2: Placebo to MK1775 capsules 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has advanced, metastatic, and recurrent squamous cell, adenosquamous, or adeno-carcinoma of the uterine cervix (Stage II - IVb)
  • Patient has received cisplatin in combination with radiation as initial or adjuvant treatment for their cervical cancer
  • Patient 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
  • Patient has measurable disease
  • Patient's performance status on the Eastern Cooperative Oncology Group (ECOG) Performance Scale is less than or equal to 1
  • Patient has a negative pregnancy test within 72 hours of the first dose of study medication

Exclusion Criteria:

  • Patient has had chemotherapy, radiotherapy, or biological therapy within 6 months of entering the study
  • Patient has a history of vascular thrombotic events or vascular reconstruction
  • Patient has active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Patient has a primary CNS tumor
  • Patient requires the use of medications or products that are metabolized by, or inhibit or induce CYP3A4 (Cytochrome P450 3A4)
  • Patient is expecting to reproduce within the duration of the study or is pregnant or breastfeeding
  • Patient is known to be Human Immunodeficiency Virus (HIV)-positive
  • Patient has known active Hepatitis B or C
  • Patient has a known history of interstitial lung disease or pulmonary fibrosis
  • Patient has symptomatic ascites or pleural effusion
  • Patient has a clinical history suggestive of Li-Fraumeni Syndrome
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Vice President, Late State Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT01076400     History of Changes
Other Study ID Numbers: 2010_515, MK1775-008
Study First Received: February 24, 2010
Last Updated: June 22, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Cisplatin
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014