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

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

panitumumab

erlotinib hydrochloride

irinotecan hydrochloride

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Cancer Care & Hematology Specialists of Chicagoland
Northwestern University, Northwestern Medical Faculty Foundation
Hematology/Oncology Associates
Joliet Oncology-Hematology Associates, Ltd.
Hope Cancer Center
Cancer Center of Kansas
Nebraska Methodist Hospital
Virtua Memorial (Regional Cancer Care Associates of Mount Holly)
Mercy Clinic Oncology and Hematology
The Jones Clinic

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Arm A: Erlotinib + Panitumumab + Irinotecan

Arm B: Erlotinib + Panitumumab

Arm C: Erlotinib + Panitumumab

Arm Description

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.

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.

Patients receive erlotinib hydrochloride and panitumumab as in arm B.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Time to Disease Progression

Time to disease progression 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 . Time to disease progression will be defined as the time elapsed from the day of 1st study drug administration to the day disease progression is documented or death occurs and will . Progressive Disease will be defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) : At least a 20% increase in the sum of the longest diameter (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.

Time to Treatment Failure

Time to treatment failure will be measured as the time elapsed from the day of first study drug administration to the date a subject stops all study drugs for any reason.

Toxicity of the Combination of Study Drugs

Data on the toxicity of the combination of study drugs is assessed by laboratory blood draws done on day 1 of every treatment cycle and by patient report while on study treatment and up to 30 days after the last treatment. Grade 3 and grade 4 adverse events (AE) where the relationship between the AE and at least one of the study drugs were considered to be definite, probable or possible, were collected using National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). AEs are graded as: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

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

Effect on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition. Skin biopsies will be performed at baseline (before the first days of treatment) and and at a time-point reflecting maximum rash intensity determined by a dermatologist.

Full Information

NCT ID

NCT00940316

First Posted

July 15, 2009

Last Updated

April 16, 2019

Sponsor

Northwestern University

Collaborators

Genentech, Inc., OSI Pharmaceuticals, Amgen

1. Study Identification

Unique Protocol Identification Number

NCT00940316

Brief Title

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

Official Title

A Randomized Phase II Study of Dual Epidermal Growth Factor Receptor Inhibition With Erlotinib and Panitumumab With or Without Irinotecan as Second Line Therapy in Patients With Metastatic Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

January 18, 2010 (Actual)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Northwestern University

Collaborators

Genentech, Inc., OSI Pharmaceuticals, Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

OBJECTIVES: Primary Determine the response rate in patients with metastatic colorectal cancer treated with erlotinib hydrochloride and panitumumab with versus without irinotecan hydrochloride as second-line therapy . Secondary Determine time to disease progression and time to treatment failure in patients treated with these regimens. Determine the safety of these regimens in these patients. Determine the effect of these regimens on downstream targets of EGFR in skin rash associated with pharmacologic EGFR inhibition (exploratory). Determine the association between KRAS mutations and response to EGFR inhibition (exploratory). OUTLINE: This is a multicenter study. Patients are stratified according to wild-type Kras tumors ( 6/6 UGT1A1 vs 6/7 UGT1A1), and are randomized to 1 of 2 treatment arms. Patients with wild-type Kras tumor 7/7 UGT1A1 receive treatment in arm III. Arm I: 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. Arm II: 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 I. Arm III: Patients receive erlotinib hydrochloride and panitumumab as in arm II. Skin biopsies and blood samples may be collected for further analysis. After completion of study therapy, patients are followed every 6 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Erlotinib + Panitumumab + Irinotecan

Arm Type

Experimental

Arm Description

Arm Title

Arm B: Erlotinib + Panitumumab

Arm Type

Experimental

Arm Description

Arm Title

Arm C: Erlotinib + Panitumumab

Arm Type

Experimental

Arm Description

Patients receive erlotinib hydrochloride and panitumumab as in arm B.

Intervention Type

Biological

Intervention Name(s)

panitumumab

Other Intervention Name(s)

Vectibix

Intervention Description

Given intravenously 6mg/kg every 2 weeks

Intervention Type

Drug

Intervention Name(s)

erlotinib hydrochloride

Other Intervention Name(s)

Tarceva

Intervention Description

Given orally 150mg daily

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Other Intervention Name(s)

Camptosar, CPT-11

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Time to Disease Progression

Description

Time Frame

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

Title

Time to Treatment Failure

Description

Time to treatment failure will be measured as the time elapsed from the day of first study drug administration to the date a subject stops all study drugs for any reason.

Time Frame

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

Title

Toxicity of the Combination of Study Drugs

Description

Time Frame

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.

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Al Benson, MD

Organizational Affiliation

Northwestern University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cancer Care & Hematology Specialists of Chicagoland

City

Arlington Heights

State/Province

Illinois

ZIP/Postal Code

60005

Country

United States

Facility Name

Northwestern University, Northwestern Medical Faculty Foundation

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611-3013

Country

United States

Facility Name

Hematology/Oncology Associates

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Joliet Oncology-Hematology Associates, Ltd.

City

Joliet

State/Province

Illinois

ZIP/Postal Code

60435

Country

United States

Facility Name

Hope Cancer Center

City

Terre Haute

State/Province

Indiana

ZIP/Postal Code

47802

Country

United States

Facility Name

Cancer Center of Kansas

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67214

Country

United States

Facility Name

Nebraska Methodist Hospital

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68114

Country

United States

Facility Name

Virtua Memorial (Regional Cancer Care Associates of Mount Holly)

City

Mount Holly

State/Province

New Jersey

ZIP/Postal Code

08060

Country

United States

Facility Name

Mercy Clinic Oncology and Hematology

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73120-9309

Country

United States

Facility Name

The Jones Clinic

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38138

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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