Phase I/Randomized Phase II Study of Second Line Therapy With Irinotecan + Cetuximab +/- RAD001 for Colorectal Cancer

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The addition of RAD001, an mTOR inhibitor, to irinotecan and anti-EGFR antibody cetuximab may increase efficacy for patients with metastatic colorectal cancer who progressed on prior chemotherapy. This approach is biologically directed to overall target the cancer cell at multiple levels, and potentially preventing chemotherapy and EGFR-therapy resistance.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoosier Cancer Research Network
• Collaborators: Novartis Pharmaceuticals; Pfizer
• Treatments: Camptothecin; Cetuximab; Everolimus; Irinotecan; Sirolimus

Criteria

Inclusion Criteria:

• Histological or cytological proof of colon or rectal adenocarcinoma

• Measurable site of disease according to RECIST that has not been previously irradiated

• Must have metastatic colorectal cancer which progressed after first line chemotherapy +/- bevacizumab

• Blood sample collected within 21 days prior to being registered for protocol therapy for UTG1A1 genotype analysis. (Patients with the UGT1A1 *28 7/7 genotype (homozygosity for the TA7 allele) will be excluded from the Phase I stage of the study. During the Phase II stage of the study, subjects will be allowed to participate but must begin treatment at dose level -1 of irinotecan.)

• A history of other malignancies (non-colorectal) is allowed, provided it has been curatively treated and demonstrates no evidence for recurrence of that cancer

• Prior radiation therapy allowed to < 25% of the bone marrow

• Age ≥ 18 years at the time of consent

• Written informed consent and HIPAA authorization for release of personal health information

• Females of childbearing potential and males must be willing to use an effective method of contraception

• Females of childbearing potential must have a negative pregnancy test within 7 days of being registered for protocol therapy

Exclusion Criteria:

• No more than one prior chemotherapy regimen for metastatic colorectal cancer, at least 28 days prior to being registered for protocol therapy

• No prior treatment with cetuximab

• No prior treatment with an mTOR inhibitor

• No known hypersensitivity to cetuximab, RAD001 (everolimus), other rapamycins (sirolimus, temsirolimus) or to its excipients

• No treatment with any investigational agent within 28 days prior to being registered for protocol therapy

• No symptomatic brain metastasis

• No uncontrolled diabetes as defined by a fasting serum glucose >1.5 x ULN

• No chronic treatment with systemic steroids or another immuno-suppressive agent

• No serious non-healing wound, ulcer, bone fracture, major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to being registered for protocol therapy

• No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis

• No active bleeding or a pathological condition that is associated with a high risk of bleeding

• No uncontrolled systemic disease including active infections or uncontrolled hypertension

• No known history of HIV seropositivity

• No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

• No nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with protocol therapy

• No planned immunization with attenuated live viruses during the study period

• Females must not be breastfeeding