A Study of Dalotuzumab + MK-2206, Dalotuzumab + MK-0752, and Dalotuzumab + Ridaforolimus Combination Therapies in Participants With Advanced Cancer (MK-0646-027)
Condition: Neoplasms Malignant
MeSH terms: Neoplasms
Intervention: dalotuzumab; MK-0752; ridaforolimus; MK-2206
Intervention description: Administered intravenously (IV) once weekly in 28-day cycles for a maximum of 6 months of study therapy; Administered orally (PO) weekly in 28-day cycles for a maximum of 6 months of study therapy; Administered PO daily for 5 consecutive days per week in 28-day cycles for a maximum of 6 months of study therapy; Administered PO weekly in 28-day cycles for a maximum of 6 months of study therapy
Intervention MeSH terms: 3-(4-((4-chlorophenyl)sulfonyl)-4-(2,5-difluorophenyl)cyclohexyl)propanoic acid
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal cancer; Solid tumors; Ovarian cancer; Fallopian tube cancer; Primary peritoneal cancer

Summary:

      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 + ridaforolimus
      (MK-8669). Part 1 of 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 (MTD) of each combination. Part 2 of the study will assess preliminary
      anti-tumor activity of these combinations (at MTD) in two groups of participants with
      selected tumor biomarkers: 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 + ridaforolimus 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.

      The primary hypothesis is that the DLTs observed in adult patients with locally advanced or
      metastatic solid tumors after administration of each of the MK-MK doublets will be
      dose-dependent to allow for definition of a MTD within each MK-MK doublet.
    

Eligibility 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 1:

          -  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 2:

          -  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.