Study of FOLFIRI Plus Cetuximab Plus IMO-2055 in Patients With Colorectal Cancer

NCT00719199 | Terminated Phase 1

• 2 other identifiers: IMO-2055-210EMR200068_210
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

Open-label phase 1b trial. Study treatment will be administered in 3 week cycles. There are two distinct parts in this study:

• Part 1: Dose escalation from IMO-2055
• Part 2: Once a recommended phase 2 dose is found additional tolerability and pharmacodynamics will be explored

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; metastatic cancer; prior therapy; 1b

Outcome Measures

Primary Outcomes (1)

• • The primary objective of this study is to determine the recommended phase 2 dose of IMO 2055 when combined with FOLFIRI and cetuximab in patients with histologically proven advanced or metastatic colorectal cancer (CRC).

  10 months from first patient in, Oct 2010

Secondary Outcomes (7)

• • To evaluate the safety of weekly IMO 2055 combined with FOLFIRI plus cetuximab.

  Assessed weekly at patient visits

• • To investigate the pharmacokinetics (PK) of IMO-2055.

  Assessed weekly at patient visits until Cycle 4

• • To investigate the tolerability and pharmacodynamic (PD) effects of dexamethasone scheduling with IMO 2055 and FOLFIRI.

  Assessed weekly at patient visits until Cycle 4

• • To investigate potential signs of efficacy using the Response Evaluation Criteria for Solid Tumors (RECIST) response rate in patients with measurable disease.

  Every six weeks

• • To investigate progression-free survival (PFS) and overall survival for up to one year in all patients.

  Every three months

Study Arms (1)

1

EXPERIMENTAL

IMO 2055 is a novel phosphorothioate oligodeoxynucleotide that is an agonist of Toll-like Receptor 9 (TLR9).

Drug: IMO-2055; Drug: Cetuximab; Drug: FOLFIRI

Interventions

IMO-2055 DRUG

SC weekly injections

1

Cetuximab DRUG

given weekly through intravenous administration. Cycle 1 Day 1 dose given at 400mg/m2, all subsequent doses given at 250 mg/m2.

1

FOLFIRI DRUG

Given day 1 of each cycle

1

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent prior to any study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
• Male or female patients aged ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed adenocarcinoma of the colon or rectum with advanced or metastatic disease.
• Patients whose disease has recurred or progressed during or after completion of at least one (1) standard regimen of cytotoxic agents. Patients may have had any number of prior regimens as long as the other entry criteria are met. Preferred patients are those who have progressed on first line FOLFIRI or FOLFOX with or without bevacizumab. Patients may have had prior exposure to monoclonal antibodies such as cetuximab, bevacizumab or panitumumab.
• All clinically significant adverse events of any prior chemotherapy, surgery or radiotherapy must have resolved to CTCAE v3.0 grade ≤ 1. Neuropathy of CTCAE v3.0 grade ≤ 2 will be allowed but the neuropathy should be closely monitored throughout the trial.
• A minimum of 4 weeks must occur between last receipt of chemotherapy, biotherapy, radiotherapy, or major surgery and registration.
• Be willing and able to comply with the protocol for the duration of the study.
• If prior malignancy was diagnosed, other than colorectal, no evidence of disease from that cancer, off all therapy for that cancer and recovered to grade 1 or less toxicity from prior treatment.

You may not qualify if:

• Patients with any of the following will be excluded from participation in the study:
• Disease
• Known central nervous system (CNS) metastases unless controlled for ≥ 4 months without the use of steroids.
• Patients who are candidates for neoadjuvant "conversion" therapy followed by curative surgery.
• Prior Treatments
• Prior pelvic irradiation.
• Administration of any investigational agent (therapeutic or diagnostic), within 4 weeks prior to first study dosing.
• Patients with a prior history of cetuximab hypersensitivity may be admitted to Part 1 of the study only.
• Other Concomitant Medications
• Chronic oral or intravenous corticosteroids. (Note: Doses ≤ 5 mg/day of prednisone or equivalent are permitted. Topical, inhaled and intra-articular corticosteroids are allowed.)
• Therapeutic anticoagulation (warfarin \> 1 mg/day or heparin). Low-dose warfarin for port prophylaxis and low-molecular weight heparin at therapeutic doses are allowed.
• Laboratory
• The following laboratory results:
• Hemoglobin \< 9.0 g/dL Absolute neutrophil count \< 1.5 x 109/L Platelet count \< 100 x 109/L
• Total bilirubin \> 1.5 x upper limit of normal (ULN)

Sponsors & Collaborators

• EMD Serono: lead

Study Sites (5)

Georgetown University Lombardi Cancer Center

Washington D.C., District of Columbia, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Cancer Therapy & Research Center

San Antonio, Texas, 78229, United States

Location

Cancer Therapy and Research Center

San Antonio, Texas, United States

Location

Related Publications (1)

• Chan E, Kwak EL, Hwang J, Heiskala M, de La Bourdonnaye G, Mita M. Open-label phase 1b study of FOLFIRI plus cetuximab plus IMO-2055 in patients with colorectal cancer who have progressed following chemotherapy for advanced or metastatic disease. Cancer Chemother Pharmacol. 2015 Apr;75(4):701-9. doi: 10.1007/s00280-015-2682-2. Epub 2015 Jan 28.

  PMID: 25627002 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

IMO-2055; Cetuximab; IFL protocol

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Phil Breitfeld, MD

  EMD Serono

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 17, 2008
• First Posted: July 21, 2008
• Study Start: January 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 22, 2013

Record last verified: 2013-10

Locations

US (5)