Clinical trial NCT01609231: A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
Official title: A Phase IIA Open Label, Adaptive, Randomized Clinical Trial of Dalotuzumab (MK-0646) Treatment in Combination With Irinotecan Versus Cetuximab and Irinotecan for Patients With Metastatic Rectal Cancers (mRC) Expressing High IGF-1/Low IGF-2 Levels
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rectal Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-05-31
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Assessment of Progression-free Survival (PFS)
timeFrame: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
Secondary outcomes:
measure: Percentage of Participants With Objective Response Rate (ORR)
timeFrame: From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: