Know Cancer

or
forgot password

Phase I / Randomized Phase II Study of Second Line Therapy With Irinotecan and Cetuximab With or Without RAD001, an Oral mTOR Inhibitor for Patients With Metastatic Colorectal Cancer: Hoosier Oncology Group GI05-102


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer

Thank you

Trial Information

Phase I / Randomized Phase II Study of Second Line Therapy With Irinotecan and Cetuximab With or Without RAD001, an Oral mTOR Inhibitor for Patients With Metastatic Colorectal Cancer: Hoosier Oncology Group GI05-102


OUTLINE: This is a multi-center study.

PHASE I:

- UGT1A1 *28 7/7 genotype IS NOT present

- Cetuximab 250 mg/m2 IV days 1, 8, and 15

- Irinotecan 125 mg/m2 IV days 1 and 8

- RAD001 PO QD (dose determined at the time of registration; subjects will remain at this
dose level until treatment discontinuation)

PHASE II:

- Randomization based on UGT1A1 *28 7/7 Genotype or Prior Irinotecan Exposure

ARM A:

- Cetuximab 250 mg/m2 IV days 1, 8, and 15

- Irinotecan 125 mg/m2 IV days 1 and 8

AT TIME OF PROGRESSIVE DISEASE, ARM A TREATMENT WILL CROSSOVER:

- Cetuximab 250 mg/m2 IV days 1, 8, and 15

- Irinotecan 125 mg/m2 IV days 1 and 8

- RAD001 PO QD (maximum tolerated dose)

ARM B:

- Cetuximab 250 mg/m2 IV days 1, 8, and 15

- Irinotecan 125 mg/m2 IV days 1 and 8

- RAD001 PO QD (maximum tolerated dose)

AT TIME OF PROGRESSIVE DISEASE, ARM B TREATMENT WILL BE DISCONTINUED

ECOG performance status 0-2

Life Expectancy: Not specified

Hematopoietic:

- Absolute neutrophil count (ANC) ≥ 1,500 mm3

- Platelets ≥ 100,000 mm3

- Hemoglobin (Hgb) ≥ 9 g/dL

- White blood cell count (WBC) ≥ 2,000 mm3

- INR < 1.5 x upper limit of normal (ULN) if not on anticoagulation (if on
anticoagulation must have an in-range INR (usually between 2 and 3) on a stable dose of
warfarin)

- PTT < 1.5 x ULN

Hepatic:

- Bilirubin ≤ 1.5 x ULN

- Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN

- Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN

- Albumin ≥ 3.0 g/dL

Renal:

- Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula

Cardiovascular:

- No uncontrolled cardiac arrhythmia requiring medication, transient ischemic attack
(TIA), or cerebrovascular accident (CVA) within 6 months prior to being registered for
protocol therapy

- No uncontrolled congestive heart failure, myocardial infarction, or unstable angina
within 6 months prior to being registered for protocol therapy

Pulmonary:

- No severely impaired lung function as demonstrated by pulse O2 saturation ≤ 90% at rest
on room air, or pulmonary function test FEV1 ≤ 2L

- No history of prior chronic lung infection such as tuberculosis, atypical tuberculosis,
or histoplasmosis as evidenced by a chest CT or x-ray within 21 days prior to being
registered for protocol therapy


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the MTD of RAD001 in combination with irinotecan and cetuximab as second line therapy in patients with metastatic colorectal cancer

Outcome Time Frame:

Phase I

Safety Issue:

Yes

Principal Investigator

Gabriela Chiorean, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Hoosier Oncology Group, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

GI05-102

NCT ID:

NCT00522665

Start Date:

August 2007

Completion Date:

June 2013

Related Keywords:

  • Colorectal Cancer
  • Colorectal Neoplasms

Name

Location

Siteman Cancer CenterSaint Louis, Missouri  63110
Northwestern University Feinberg School of MedicineChicago, Illinois  60611
Arnett Cancer CareLafayette, Indiana  47904
Northern Indiana Cancer Research ConsortiumSouth Bend, Indiana  
Medical & Surgical Specialists, LLCGalesburg, Illinois  61401
Cancer Care Center Of Southern IndianaBloomington, Indiana  47403
Horizon Oncology CenterLafayette, Indiana  47905
Oncology Hematology Associates of SW IndianaEvansville, Indiana  47714
Community Regional Cancer CenterIndianapolis, Indiana  46256
Center for Cancer Care, Inc., P.C.New Albany, Indiana  47150
Indiana University Simon Cancer CenterIndianapolis, Indiana  46202
IN Onc/Hem AssociatesIndianapolis, Indiana  46202
St. Vincent Hospital & Health CentersIndianapolis, Indiana  46206
Monroe Medical AssociatesMunster, Indiana  46321