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A Study of Dalotuzumab + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + MK-8669 Combination Therapies in Participants With Advanced Cancer (MK-0646-027)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01243762
First received: November 17, 2010
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

This is an open-label, two-part study to evaluate the safety and tolerability of combination treatment with dalotuzumab + MK-2206, dalotuzumab + MK-0752, or dalotuzumab + MK-8669 (ridaforolimus). The study will determine the dose limiting toxicities (DLTs) observed after administration of each of the combinations at various doses and define the maximum tolerated dose of each combination. Preliminary anti-tumor activity of these combinations, in two groups of participants having selected tumor biomarkers, will be assessed: one group with metastatic or recurrent platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and one group with metastatic or recurrent colorectal cancer. The dalotuzumab + MK-8669 and dalotuzumab + MK-2206 arms will be enriched with female platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer participants. The dalotuzumab + MK-0752 arm will be enriched with metastatic or recurrent wild-type kirsten rat sarcoma (KRAS) colorectal cancer participants.


Condition Intervention Phase
Neoplasms Malignant
Drug: dalotuzumab + MK-2206
Drug: dalotuzumab + MK-0752
Drug: Dalotuzumab + MK-8669 (ridaforolimus)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Parallel Arm Study of MK-0646 (Dalotuzumab) + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + MK-8669 (Ridaforolimus) Doublets (MK-MK Doublets) in Patients With Advanced Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants whose best response is a partial response (PR) or complete response (CR) [ Time Frame: Tumor assessments will be performed at baseline, the end of Cycle 2, and every two cycles during treatment (1 cycle = 28 days). ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: November 2010
Study Completion Date: March 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: dalotuzumab + MK-2206
Dose escalation for dalotuzumab + MK-2206 combination; participants will be enrolled and treated at sequentially rising dose levels of dalotuzumab + MK-2206 until a maximum tolerated dose is identified.
Drug: dalotuzumab + MK-2206
Dalotuzumab (MK-0646) intravenously once weekly and MK-2206 by mouth once weekly in 28-day cycles
Other Name: MK-0646
Experimental: Part A: dalotuzumab + MK-0752
Dose escalation for dalotuzumab + MK-0752 combination; participants will be enrolled and treated at sequentially rising dose levels of dalotuzumab + MK-0752 until a maximum tolerated dose is identified.
Drug: dalotuzumab + MK-0752
Dalotuzumab (MK-0646) intravenously once weekly and MK-0752 by mouth once weekly in 28-day cycles
Other Name: MK-0646
Experimental: Part B: dalotuzumab + MK-2206 - ovarian cancer cohort
Dose confirmation in female participants with platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; participants will be enrolled and treated at the maximum tolerated dose determined in Part A
Drug: dalotuzumab + MK-2206
Dalotuzumab (MK-0646) intravenously once weekly and MK-2206 by mouth once weekly in 28-day cycles
Other Name: MK-0646
Experimental: Part B: dalotuzumab + MK-0752 - colorectal cancer cohort
Dose confirmation in participants with wild-type KRAS colorectal cancer; participants will be enrolled and treated at the maximum tolerated dose determined in Part A
Drug: dalotuzumab + MK-0752
Dalotuzumab (MK-0646) intravenously once weekly and MK-0752 by mouth once weekly in 28-day cycles
Other Name: MK-0646
Experimental: Part B: dalotuzumab + MK-8669 (ridaforolimus)
Dose confirmation in female participants with platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer; this arm will be enriched with platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer participants.
Drug: Dalotuzumab + MK-8669 (ridaforolimus)
Dalotuzumab (MK-0646) intravenously once weekly and MK-8669 orally daily for 5 consecutive days per week in 28-day cycles
Other Name: MK-0646

  Eligibility

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

Inclusion Criteria:

  • Participants must not have any medical conditions that may impact compliance with the protocol, limit interpretation of study results, or pose an unacceptable medical risk.
  • Participant must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (EGOG) Performance Scale.
  • Participant is able to swallow capsules and has no condition that will preclude swallowing and absorbing oral medications on an ongoing basis
  • Participant has no history of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma with prostatic specific antigen (PSA) < 1.0; or has undergone potentially curative therapy with no evidence of that disease for five years, or is deemed at low risk for recurrence by his/her treating physician.
  • Participant has at least one measurable metastatic or recurrent lesion according to Response Criteria in Solid Tumors (RECIST)

Part A:

- Participant must have a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist, or participant is not a candidate for standard therapy, or is unwilling to undergo standard therapy. There is no limit on the number of prior treatment regimens.

Part B:

  • A female participant assigned to the dalotuzumab + MK-2206 or dalotuzumab + ridaforolimus treatment arms must have histologically-confirmed metastatic or recurrent platinum-resistant ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist, or participant is not a candidate for standard therapy, or is unwilling to undergo standard therapy. Participants may have received any number of prior treatment regimens.
  • A participant assigned to the dalotuzumab + MK-0752 treatment arms must have histologically-confirmed metastatic or recurrent wild-type KRAS colorectal cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist, or participant is not a candidate for standard therapy, or is unwilling to undergo standard therapy. Participants may have received any number of prior treatment regimens.
  • Participant agrees to provide archival tumor tissue sample or undergo biopsy for analysis of gene expression levels.

Exclusion Criteria:

  • Participant has had chemotherapy, radiotherapy, or biological therapy (including monoclonal antibodies) within 4 weeks prior to study Day 1 (6 weeks for nitrosoureas or mitomycin C) or who has not recovered from adverse events due to agents administered more than 4 weeks earlier, or major surgery <4 weeks earlier.
  • Participant is currently participating or has participated in a study with an investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Participants previously treated with a monoclonal antibody will be eligible to participate after a 28 day washout period.
  • Participants with known central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded.
  • Participant has significant or uncontrolled cardiovascular disease, including New York Heart Association (NYHA) Class III-IV heart failure, unstable angina, or a myocardial infarction within the last 6 months.
  • Participant is known to have diabetes that is poorly controlled
  • Participant is pregnant, breastfeeding, or expecting to conceive or father children during the study
  • Participant is known to be human immunodeficiency virus (HIV)-positive
  • Participant has active Hepatitis B or C infection
  • Participant has symptomatic ascites or pleural effusion
  • Participant requires treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for at least two weeks prior to the first dose of study drug
  • Participant requires treatment with medication(s) that strongly or moderately induce or inhibit cytochrome P450
  • Participant is using growth hormone or growth hormone inhibitors
  • Participant requires treatment with therapeutic warfarin
  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: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01243762     History of Changes
Other Study ID Numbers: 0646-027
Study First Received: November 17, 2010
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Colorectal cancer
Solid tumors
Ovarian cancer
Fallopian tube cancer
Primary peritoneal cancer

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014