Erlotinib, Modified FOLFOX6, and Bevacizumab as First-Line Therapy Metastatic Colorectal Cancer

NCT00118261 | Completed Phase 1 DMC

• 3 other identifiers: CASE2204P30CA043703NCI-2009-01287
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may help chemotherapy work better by making tumor cells more sensitive to the drugs. Giving erlotinib together with combination chemotherapy and bevacizumab may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given together with combination chemotherapy and bevacizumab as first-line therapy in treating patients with metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

stage IV rectal cancer; stage IV colon cancer; recurrent rectal cancer; recurrent colon cancer

Outcome Measures

Primary Outcomes (1)

• Number of patients that develop study drug related toxicity

  Dose-limiting toxicities will be tracked in the first three cycles. The occurrence of DLT in 2 of the first 6 patients, 3 of the first 9 patients, or 4 of the first 12 patients (whichever occurs soonest)will require that subsequent patients are enrolled to the study at 100 mg erlotinib daily.

  3 courses (6 weeks)

Secondary Outcomes (2)

• Patient Response to Treatment Measured by RECIST Criteria

  3 courses (6 weeks)

• Number of patients that can increase the erlotinib dose to 200mg

  14 days

Study Arms (1)

Erlotinib, modified FOLFOX6, and bevacizumab

EXPERIMENTAL

Biological: bevacizumab; Drug: erlotinib hydrochloride; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin

Interventions

bevacizumab BIOLOGICAL

Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Erlotinib, modified FOLFOX6, and bevacizumab

erlotinib hydrochloride DRUG

Courses 1-3: oral erlotinib once daily on days 1-14. Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Erlotinib, modified FOLFOX6, and bevacizumab

fluorouracil DRUG

Starting with course 2: fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Erlotinib, modified FOLFOX6, and bevacizumab

leucovorin calcium DRUG

Starting with course 2: Leucovorin calcium IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Erlotinib, modified FOLFOX6, and bevacizumab

oxaliplatin DRUG

Starting with course 2: oxaliplatin IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Erlotinib, modified FOLFOX6, and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed colorectal cancer * Biopsy-accessible metastatic disease * Measurable disease * No CNS metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * At least 3 months Hematopoietic * WBC ≥ 4,000/mm\^3 OR * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 10 g/dL * No bleeding disorder Hepatic * Bilirubin ≤ 1.5 mg/dL * Albumin ≥ 2.5 g/dL Renal * Creatinine ≤ 1.5 mg/dL * Urine protein:creatine ratio \< 1.0 Cardiovascular * Blood pressure ≤ 150/100 mmHg * No arterial thrombotic event within the past 6 months * No New York Heart Association grade II-IV congestive heart failure Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 1 month after completion of study treatment * No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other malignancy with \< 10% chance of relapse within 3 years * No uncontrolled infection * No severe uncontrolled illness that would preclude study participation * No peripheral neuropathy interfering with function * No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months * No serious non-healing wound, ulcer, or bone fracture PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent immunotherapy * No concurrent sargramostim (GM-CSF) Chemotherapy * No prior chemotherapy, including oxaliplatin, for metastatic disease * Prior adjuvant oxaliplatin allowed provided disease progressed \> 12 months after completion of oxaliplatin * At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) * No more than 2 courses of prior mitomycin * No concurrent chemotherapy Endocrine therapy * No concurrent anticancer hormonal therapy Radiotherapy * At least 2 weeks since prior radiotherapy * No prior radiotherapy to \> 15% of bone marrow * No concurrent radiotherapy Surgery * At least 4 weeks since prior major surgery * At least 1 week since prior minor surgery Other * Recovered from prior therapy * No prior epidermal growth factor receptor inhibitor therapy * No other concurrent antineoplastic or antitumor therapy * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MetroHealth Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

UHHS Chagrin Highlands Medical Center

Cleveland, Ohio, 44122, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms; Colonic Neoplasms

Interventions

Bevacizumab; Erlotinib Hydrochloride; Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Smitha Krishnamurthi, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2005
• First Posted: July 11, 2005
• Study Start: March 1, 2005
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: September 3, 2012

Record last verified: 2012-08

Locations

US (3)