Pertuzumab and Cetuximab in Treating Patients With Previously Treated Locally Advanced or Metastatic Colorectal Cancer

NCT00551421 | Completed Phase 1 Results DMC

• 3 other identifiers: NCI-2009-0024107-070U01CA062490
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Monoclonal antibodies, such as pertuzumab and cetuximab, 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. Giving pertuzumab together with cetuximab may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of pertuzumab when given together with cetuximab and to see how well they work in treating patients with previously treated locally advanced or metastatic colorectal cancer

Conditions

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage III Colon Cancer; Stage III Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose of Pertuzumab When Administered in Combination With Cetuximab (Phase I)

  The regimen was deemed intolerable so there was no recommended phase II dose.

  28 days

• Objective Tumor Response Rate Defined as the Proportion of Patients With a Best Overall Response of CR or PR, Per RECIST Criteria (Phase II)

  Objective tumor response rate defined as the proportion of patients with a best overall response of CR or PR, per RECIST criteria (Phase II).

  Best tumor response from time period of start of study treatment to study discontinuation.

Secondary Outcomes (2)

• Progression-free Survival

  The duration of time from start of study treatment to time of objective disease progression or death.

• Overall Survival

  The duration of time from start of study treatment to death from any cause.

Study Arms (1)

Arm I

EXPERIMENTAL

Phase I: Patients receive pertuzumab IV over 30-60 minutes on day 1. Patients also receive cetuximab IV over 60-120 minutes on days 2, 8, and 15 of course 1 and on days 1, 8, and 15 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Phase II: Patients receive treatment as in phase I. Pertuzumab is administered at the recommended phase II dose (determined in phase I).

Biological: pertuzumab; Biological: cetuximab; Drug: irinotecan hydrochloride; Other: immunohistochemistry staining method; Other: fluorescence in situ hybridization; Other: gene expression analysis; Other: mutation analysis; Other: polymerase chain reaction; Other: laboratory biomarker analysis

Interventions

pertuzumab BIOLOGICAL

Given IV

Also known as: 2C4 antibody, monoclonal antibody 2C4, Perjeta, rhuMAb-2C4

Arm I

cetuximab BIOLOGICAL

Given IV

Also known as: C225, C225 monoclonal antibody, IMC-C225, MOAB C225, monoclonal antibody C225

Arm I

irinotecan hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E

Arm I

immunohistochemistry staining method OTHER

Correlative study

Also known as: immunohistochemistry

Arm I

fluorescence in situ hybridization OTHER

Correlative study

Also known as: fluorescence in situ hybridization (FISH)

Arm I

gene expression analysis OTHER

Correlative study

Arm I

mutation analysis OTHER

Correlative study

Arm I

polymerase chain reaction OTHER

Correlative study

Also known as: PCR

Arm I

laboratory biomarker analysis OTHER

Correlative study

Arm I

Eligibility Criteria

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

You may qualify if:

• Patients with a history of colorectal cancer (CRC) treated by surgical resection and who develop radiological or clinical evidence of metastatic disease do not require separate histological or cytological confirmation of metastatic disease unless 1 of the following criteria are met:
• More than 5 years has elapsed between the primary surgery and the development of metastatic disease
• The primary cancer was stage I
• Patients must have representative tumor specimens in paraffin blocks or at least 15 unstained slides with an associated pathology report obtained at any time prior to study entry:
• Cytology specimens are not acceptable replacements
• Patients must have their tumor tissue screened for KRAS mutation status, and be found to have a KRAS wild-type tumor:
• No KRAS-mutated tumor
• Locally advanced or metastatic disease
• Not curable by surgery or amenable to radiotherapy with curative intent
• Must have received an cetuximab-containing regimen for at least 6 weeks for treatment of metastatic disease
• Documented progression of disease or intolerable toxicity during or within 3 months of receiving this regimen
• Patients who have received an cetuximab-containing regimen as adjuvant therapy for resected stage II or III CRC are eligible provided recurrent disease is documented \< 6 months after completion of adjuvant treatment
• Must have received \>= 1 prior chemotherapeutic regimen for treatment of metastatic disease with any of the following:
• Cetuximab
• Must have resolution of any skin rash related to prior treatment with cetuximab

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

pertuzumab; 2C4 antibody; Cetuximab; Irinotecan; Immunohistochemistry; In Situ Hybridization, Fluorescence; Gene Expression Profiling; Polymerase Chain Reaction

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; 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; Camptothecin; Alkaloids; Heterocyclic Compounds; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytogenetic Analysis; Genetic Techniques; Nucleic Acid Hybridization; Nucleic Acid Amplification Techniques

Limitations and Caveats

Combination intolerable due to overlapping toxicities of diarrhea, rash and mucositis; a unique rash with desquamation seen in most patients across all dose levels. Correlative study inconclusive with too few patients and timepoints with results.

Results Point of Contact

• Title: Dr. Kimmie Ng
• Organization: Dana-Farber Cancer Institute

kimmie_ng@dfci.harvard.edu

617-632-4150

Study Officials

• Kimmie Ng

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2007
• First Posted: October 31, 2007
• Study Start: October 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: June 1, 2012
• Last Updated: March 31, 2015
• Results First Posted: February 23, 2015

Record last verified: 2014-07

Locations

US (1)