A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
Condition: Rectal Neoplasms
MeSH terms: Rectal Neoplasms
Intervention: Dalotuzumab; Irinotecan; Cetuximab
Intervention description: Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.; Irinotecan 180 mg/m^2 will be administered intravenously once every two weeks either prior to dalotuzumab (Arm A) or after cetuximab (Arm B). Pre-medication at the discretion of the investigator will follow local or country-specific standard of care.; Cetuximab will be administered intravenously prior to irinotecan at an initial dose of 400 mg/m^2 followed by weekly infusions of 250 mg/m^2. Pre-medication at the discretion of the investigator will follow local or country-specific standard of care.
Intervention MeSH terms: Irinotecan; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this adaptive trial is to compare the progression-free survival of
      participants with metastatic rectal carcinoma when treated with intravenous (IV) dalotuzumab
      (MK-0646) + irinotecan therapy relative to participants treated with IV cetuximab +
      irinotecan. The primary hypothesis is that administration of dalotuzumab in combination with
      irinotecan to participants with wild-type KRAS metastatic rectal carcinoma with high insulin
      growth factor (IGF)-1/low IGF-2 expression levels improves progression-free survival compared
      to patients treated with cetuximab in combination with irinotecan.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has metastatic colorectal cancer with primary tumor originating from the rectum

          -  Has an available archival (recent or remote) tumor, or newly obtained formalin-fixed
             tissue available for analysis for biomarker studies

          -  Has at least one measurable lesion greater than or equal to 10 mm

          -  Disease has progressed after treatment with both irinotecan- and
             oxaliplatin-containing regimens and should have progressed on or within 3 months of
             completing their last line of therapy

          -  Has a performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale

        Exclusion Criteria:

          -  Has poorly-controlled diabetes

          -  Has received chemotherapy or biological therapy within 2 weeks prior to initial dosing
             on this study, or whose toxicities from agents administered 2 weeks earlier have not
             resolved to at least grade 1 or baseline, or who is within 3 weeks from a prior
             surgery

          -  Has received radiotherapy within 2 weeks prior to initial dosing on this study, unless
             the radiotherapy was for management of pain

          -  Is currently participating or has participated in a study with an investigational
             compound or device within 30 days or 5 half-lives of the investigational agent,
             whichever is longer, of initial dosing on this study

          -  Was unable to complete previous course of irinotecan due to intolerable toxicity,
             other than discontinuation due to fatigue following prolonged administration (>4
             months exposure)

          -  Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or
             epidermal growth factor receptor (EGFR) inhibitors

          -  Has a known central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Has primary CNS tumor

          -  Has a history of a prior malignancy with the exception of cervical intraepithelial
             neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate
             carcinoma; potentially curative therapy with no evidence of that disease for 5 years,
             deemed low risk for recurrence by treating physician.

          -  Is human immunodeficiency virus (HIV)-positive

          -  Has active hepatitis B or C infection and is receiving antiviral treatment regimens

          -  Has symptomatic ascites or pleural effusion

          -  Is concurrently using growth hormone (GH), or growth hormone inhibitors