Dual Epidermal Growth Factor Receptor Inhibition With Erlotinib and Panitumumab With or Without Chemotherapy for Advanced Colorectal Cancer

NCT00940316 | Completed Phase 2 Results DMC

• 3 other identifiers: NU 07I4STU00004101OSI 4263s
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 10

Brief Summary

RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as panitumumab, 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. Panitumumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether erlotinib hydrochloride given together with panitumumab is more effective with or without irinotecan in treating patients with metastatic colorectal cancer. PURPOSE: This randomized phase II trial is studying giving erlotinib hydrochloride together with panitumumab to see how well it works with or without irinotecan hydrochloride as second-line therapy in treating patients with metastatic colorectal cancer.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Tumor Response Rate Based on Complete Response (CR)+ Partial Response (PR) + Stable Disease (SD)

  Tumor response rate will be measured by CT scan of the chest and CT scan or MRI scan of abdomen and pelvis every 8 weeks until disease progression response rate will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD)of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions,taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

  At baseline and every 8 weeks during treatment until progressive disease for maximum of 51 cycles where 1 cycle = 2 weeks.

Secondary Outcomes (4)

• Time to Disease Progression

  At baseline and every 8 weeks during treatment until disease progression and for a maximum of 51 cycles where 1 cycle = 2 weeks

• Time to Treatment Failure

  From first day of study drug treatment until the date of stopping all study drugs for any reason for a maximum of 51 cycles where 1 cycle=2weeks

• Toxicity of the Combination of Study Drugs

  Day 1 of every 2 week treatment cycle while on study treatment and 30 days after the last treatment for a maximum of 51 cycles.

• Effect on Downstream Targets of Epidermal Growth Factor Receptor (EGFR) in Skin Rash Associated With Pharmacologic EGFR Inhibition

  At baseline and at a time-point reflecting maximum rash intensity during treatment, at a maximum of 51 cycles.

Study Arms (3)

Arm A: Erlotinib + Panitumumab + Irinotecan

EXPERIMENTAL

Patients receive oral erlotinib hydrochloride once daily on days 1-14, panitumumab IV over 30-90 minutes on day 1, and irinotecan hydrochloride IV over 90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Biological: panitumumab; Drug: erlotinib hydrochloride; Drug: irinotecan hydrochloride

Arm B: Erlotinib + Panitumumab

EXPERIMENTAL

Patients receive oral erlotinib hydrochloride once daily on days 1-14 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients receive irinotecan hydrochloride as in arm A.

Biological: panitumumab; Drug: erlotinib hydrochloride; Drug: irinotecan hydrochloride

Arm C: Erlotinib + Panitumumab

EXPERIMENTAL

Patients receive erlotinib hydrochloride and panitumumab as in arm B.

Biological: panitumumab; Drug: erlotinib hydrochloride

Interventions

panitumumab BIOLOGICAL

Given intravenously 6mg/kg every 2 weeks

Also known as: Vectibix

Arm A: Erlotinib + Panitumumab + Irinotecan; Arm B: Erlotinib + Panitumumab; Arm C: Erlotinib + Panitumumab

erlotinib hydrochloride DRUG

Given orally 150mg daily

Also known as: Tarceva

Arm A: Erlotinib + Panitumumab + Irinotecan; Arm B: Erlotinib + Panitumumab; Arm C: Erlotinib + Panitumumab

irinotecan hydrochloride DRUG

Given intravenously 120mg/m2 for 6/6 genotype and 60mg/m2 for 6/7 genotype

Also known as: Camptosar, CPT-11

Arm A: Erlotinib + Panitumumab + Irinotecan; Arm B: Erlotinib + Panitumumab

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed colorectal cancer * Metastatic disease * Biopsy of either the primary cancer or metastatic site required * Tumor expressing wild-type Kras mutations * Progressive disease within 3 months after treatment with first-line fluorouracil (5-FU) and oxaliplatin-based chemotherapy OR evidence of metastatic disease within 6 months of completing adjuvant therapy with 5-FU and oxaliplatin * Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques OR as ≥ 10 mm with spiral CT scan PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy \> 6 months * ANC \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL * Creatinine \< 1.5 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN (or \< 2 mg/dL) * AST and/or ALT \< 3 times ULN (\< 5 times ULN with liver metastases) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No concurrent malignancy requiring therapy except minor surgery for non-melanoma skin cancer removal * No interstitial lung disease with symptoms (e.g., dyspnea or cough) including any of the following significant conditions: * Parenchymal lung disease * Metastatic disease * Pulmonary infections PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior EGFR inhibitors, irinotecan hydrochloride, or other second-line chemotherapy regimens * More than 4 weeks since prior radiotherapy * No other concurrent investigational agents * No other concurrent anticancer treatment modalities (e.g., radiotherapy)

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

Sponsors & Collaborators

• Northwestern University: lead
• Genentech, Inc.: collaborator
• OSI Pharmaceuticals: collaborator
• Amgen: collaborator

Study Sites (10)

Cancer Care & Hematology Specialists of Chicagoland

Arlington Heights, Illinois, 60005, United States

Location

Northwestern University, Northwestern Medical Faculty Foundation

Chicago, Illinois, 60611-3013, United States

Location

Hematology/Oncology Associates

Chicago, Illinois, 60611, United States

Location

Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, 60435, United States

Location

Hope Cancer Center

Terre Haute, Indiana, 47802, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Virtua Memorial (Regional Cancer Care Associates of Mount Holly)

Mount Holly, New Jersey, 08060, United States

Location

Mercy Clinic Oncology and Hematology

Oklahoma City, Oklahoma, 73120-9309, United States

Location

The Jones Clinic

Germantown, Tennessee, 38138, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; Erlotinib Hydrochloride; Irinotecan

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; Camptothecin; Alkaloids

Limitations and Caveats

Sponsor did not renew contract and only 28 patients of the anticipated 96 were enrolled and treated on the study.

Results Point of Contact

• Title: Dr. Al Benson
• Organization: Northwestern University

albenson@nm.org

(312) 695-0184

Study Officials

• Al Benson, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Al Benson, MD

Study Record Dates

• First Submitted: July 15, 2009
• First Posted: July 16, 2009
• Study Start: January 18, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 7, 2019
• Results First Posted: May 7, 2019

Record last verified: 2019-04

Locations

US (10)