Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Safety and Tolerability of Different Dose Combinations of Ridaforolimus With MK-2206 or MK-0752 for Participants With Advanced Cancer (MK-8669-049 AM1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01295632
First received: February 9, 2011
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

This is a two part study of the drug MK-8669 (ridaforolimus) given with MK-2206 or MK-0752. In Part A of the study, the preliminary maximum tolerated dose (MTD) of the drug combinations will be found by giving sequentially higher doses of the study drugs. An expansion cohort of participants may be enrolled to confirm the MTD. New cohorts at other dose levels may be enrolled, depending on the rate of dose limiting toxicities (DLTs) in the planned cohorts. In Part B, an assessment of the efficacy of the drug combinations against selected advanced cancers will be made so that a recommended dose to be used in Phase 2 studies (RPTD) can be found. As of 19 July 2012 the MK-0752 arms of the study were fully enrolled and closed to further recruitment. As of 30 November 2012, no additional participants with prostate cancer will be enrolled.


Condition Intervention Phase
Advanced Cancer
Drug: ridaforolimus
Drug: MK-0752
Drug: MK-2206
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 Protocol of MK-8669 (Ridaforolimus) + MK-2206 and MK-8669 (Ridaforolimus) + MK-0752 Doublets (MK-MK) 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 receiving ridaforolimus + MK-2206 who experience dose-limiting toxicities (DLTs). [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
  • Number of participants receiving ridaforolimus + MK-0752 who experience DLTs. [ Time Frame: Cycle 1 (28 days) ] [ Designated as safety issue: Yes ]
  • Number of participants whose best response is partial response (PR) or complete response (CR). [ Time Frame: Day 22-29, every other month. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the plasma concentration curve (AUC) for ridaforolimus. [ Time Frame: Part A, Cycle 0, Day 1 (pre-dose) ] [ Designated as safety issue: No ]
  • Area under the plasma concentration curve (AUC) for ridaforolimus. [ Time Frame: Part A, Cycle 0, Day 5 (pre- and post-dose) ] [ Designated as safety issue: No ]
  • AUC for the ridaforolimus + MK-0752 doublet [ Time Frame: Part A, Cycle 1, Day 1 (pre-dose) ] [ Designated as safety issue: No ]
  • AUC for the ridaforolimus + MK-0752 doublet [ Time Frame: Part A, Cycle 1, Day 12 (pre- and post-dose) ] [ Designated as safety issue: No ]

Estimated Enrollment: 124
Study Start Date: February 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ridaforolimus 20 mg + MK-2206 90 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 20 mg + MK-2206 135 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 30 mg + MK-2206 90 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 30 mg + MK-2206 135 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 30 mg + MK-2206 200 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 40 mg + MK-2206 135 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 40 mg + MK-2206 200 mg Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-2206
Tablets (5 mg, 25 mg, and 200 mg) to equal starting dose of 90 mg and escalating to 200 mg per dose, orally, once each week.
Experimental: Ridaforolimus 20 mg + MK-0752 1800 mg
No longer recruiting as of 19 July 2012
Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-0752
300 mg capsule, orally, 6 capsules per dose, once each week.
Experimental: Ridaforolimus 30 mg + MK-0752 1800 mg
No longer recruiting as of 19 July 2012
Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-0752
300 mg capsule, orally, 6 capsules per dose, once each week.
Experimental: Ridaforolimus 40 mg + MK-0752 1800 mg
No longer recruiting as of 19 July 2012
Drug: ridaforolimus
10 mg enteric-coated tablets, orally, starting dose 2 tablets and escalating to 4 tablets each day for 5 days per week.
Other Name: MK-8669
Drug: MK-0752
300 mg capsule, orally, 6 capsules per dose, once each week.

  Eligibility

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

Inclusion Criteria:

Part A of the Study:

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. Non Hodgkin Lymphoma (NHL) participants (in Part A only), must have histologically confirmed relapsed/refractory NHL. There is no limit on the number of prior treatment regimens.

Part B of the Study:

  • Participant must have performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Participant must have adequate organ function.
  • Participants must be willing to use effective methods of contraception.
  • Participant is able to swallow capsules and has no surgical or anatomical condition that will preclude the participant from 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 Prostate-Specific Antigen (PSA) <1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician.
  • Participant has at least one measurable recurrent or metastatic lesion (if a solitary lesion, histological/cytological confirmation of its neoplastic nature is required) with the exception of prostate cancer participants which do not require measurable disease if participant has PSA level of >10 ng/mL.
  • Participant must agree to provide archival or newly-obtained tumor tissue sample.

    • Ridaforolimus + MK-2206 Treatment Arm:

      • Participant must have a histologically-confirmed prostate cancer that is refractory to hormone therapy and for which the participant received any number of prior treatment regimens (no longer recruiting as of 30 November 2012), OR
      • Participant must have a histologically-confirmed breast cancer for which the participant received any number of prior treatment regimens. Archival or fresh tissue must demonstrate a low RAS-gene signature and a high Ki67 index label if estrogen receptor (ER)+
    • Ridaforolimus + MK-0752 Treatment Arm:

      • Participant must have a histologically-confirmed recurrent (either primary or secondary) glioblastoma multiforme with radiographic evidence of progression/recurrence of disease, and up to 2 prior treatment regimens for their recurrent disease, and no prior treatment with bevacizumab, OR
      • Participants must have a histologically-confirmed relapsed or refractory ovarian cancer for which the participant received no more than 2 prior treatment regiments which was either relapsed or refractory to the first line treatment.

Exclusion Criteria:

  • Participant has had chemotherapy or radiotherapy within 4 weeks prior to study Day 1 (6 weeks for nitrosoureas, mitomycin C), biological therapy (excluding antibodies) within 2 weeks prior to study Day 1, or who has not recovered (≤Grade 1 or baseline) from adverse events due to agents administered more than 4 weeks earlier. Luteinizing-hormone releasing hormone (LHRH) use by prostate cancer patients is permitted; participants with prostate cancer previously treated with flutamide or nilutamide require 4 week washout period and participants previously treated with bicalutamide require 6 week washout period before study drug administration.
  • 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 (not including monoclonal antibodies), whichever is longer, of Day 1 of this study.
  • Participants with known symptomatic or progressing Central Nervous System (CNS) metastases and/or carcinomatous meningitis are excluded. However, participants with CNS metastases who are asymptomatic and have completed a course of therapy are eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids.
  • Participant has known hypersensitivity to the components of study drug or its analogs.
  • Participant has prior exposure to agents that have the same target as to the study drug.
  • 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 a known diabetic participant who is poorly controlled at screening.
  • Participant has known psychiatric or substance abuse disorders that would interfere with compliance with study requirements.
  • Participant is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of drug or alcohol abuse.
  • Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
  • Participant is known to be Human Immunodeficiency Virus (HIV)-positive.
  • Participant has active Hepatitis B or C.
  • Participant has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions is eligible.
  • Participant has a requirement for concurrent treatment with immunosuppressive agents other than prescribed corticosteroids at stable doses for ≥ 2 weeks prior to first planned dose of study drug.
  • Participant has a requirement for concurrent treatment with medication(s) that strongly or moderate induce or inhibit cytochrome P450 (CYP3A). Participants should be off these medications ≥ 2 weeks prior to the first dose of study medication.

    • For participants with glioblastoma, dexamethasone should be discontinued at least 1 week prior to the first dose of study drugs.

For participants on the Ridaforolimus + MK-0752 treatment arm:

- Participant requires or anticipated to require concomitant therapy with enzyme-inducing antiepileptic therapy.

  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: NCT01295632     History of Changes
Other Study ID Numbers: 8669-049
Study First Received: February 9, 2011
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Recurrent glioblastoma multiforme
Hormone resistant prostate cancer
Relapsed ovarian carcinoma
Refractory ovarian carcinoma
Refractory breast cancer
Relapsed breast cancer

Additional relevant MeSH terms:
Neoplasms
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014