A Study of FOLFIRI Plus OMP-21M18 as 1st or 2nd-line Treatment in Subjects With Metastatic Colorectal Cancer

NCT01189942 | Completed Phase 1 DMC

• 1 other identifier: M18-003
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of this study is to test the safety and determine the optimal dose of a new drug, OMP-21M18, when given in combination with FOLFIRI, a standard drug treatment for advanced colorectal cancer. Participants must not have had more than one chemotherapy regimen for their metastatic disease. OMP-21M18 is a humanized monoclonal antibody (a protein made in the laboratory) developed to target cancer stem cells. The way the body handles OMP-21M18 will also be investigated. Up to 32 participants, 21 years or older, at up to 6 centres in Australia and New Zealand, will receive intravenous infusions of OMP-21M18 followed by FOLFIRI every two weeks, until disease progression or limited by drug toxicity. After 8 weeks, participants will undergo assessments to determine their disease status. If there is no evidence of disease progression participants will continue to receive infusions of OMP-21M18 and FOLFIRI every second week, until disease progression.

Conditions

Colorectal Cancer

Keywords

Phase 1; dose escalation; histologically; confirmed; malignancy; metastatic

Outcome Measures

Primary Outcomes (1)

• To the determine the maximum tolerated dose of OMP-21M18 plus FOLFIRI

  Will be done after each patient in dose cohort reaches Day 56

Secondary Outcomes (5)

• To determine the safety of FOLFIRI plus OMP-21M18 at two dose levels

  Until disease progression plus 30 days after

• To determine the rates of immunogenicity of FOLFIRI plus OMP-21M18

  Up until 12 weeks after patient has Disease Progression

• To determine population pharmacokinetics

  Until Disease Progression

• To determine the exploratory biomarker changes of FOLFIRI plus OMP 21M18

  Until Disease Progression

• To determine the preliminary efficacy of FOLFIRI plus OMP-21M18

  Until Disease Progression

Interventions

OMP-21M18 DRUG

The first 6 participants will receive OMP21M18 2.5 mg/kg once every other week, the next 6 participants will receive 5 mg/kg once every other week, and the final 6 participants will receive 10 mg/kg once every other week. A Data Safety Monitoring Board (DSMB) will review the data for the 6 participants in each dose level after the last participant in that group has been treated for 56 days and decide whether it is safe to move up to the next highest dose level. After confirming the optimum dose, 14 additional participants will be treated at the highest dose level that the DSMB considers safe.

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically confirmed metastatic colorectal cancer. Subjects may not have received more than 1 prior chemotherapy regimen for their metastatic disease and may not have received irinotecan for treatment of their metastatic disease.
• Age \>21 years
• ECOG performance status \<2 (see Appendix B)
• Life expectancy of more than 3 months
• Subjects must have normal organ and marrow function as defined below:
• Leukocytes \>3.5 x 109/L
• Absolute neutrophil count \>1.25 x 109/L
• Hemoglobin \>100 g/L
• Platelets \>125 X 109/L
• Total bilirubin \<2 X institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) \<5 X institutional ULN
• Alkaline phosphatase \<5 X institutional ULN
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within institutional ULN
• Creatinine \<1.5 X institutional ULN OR
• Calculated creatinine clearance \>60 mL/min using the Cockcroft and Gault formula as follows:

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible for participation in the study:
• Subjects receiving any other investigational agents or anti-cancer therapy.
• Subjects with brain metastases (subjects must have a CT scan or MRI of the head within 28 days prior to enrollment to rule out brain metastases), uncontrolled seizure disorder, or active neurologic disease
• History of a significant allergic reaction attributed to humanized or human monoclonal antibody therapy
• Significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women or nursing women
• Subjects with known HIV infection
• Known bleeding disorder or coagulopathy
• Subjects receiving heparin, warfarin, or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
• Subjects with known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease
• New York Heart Association Classification II, III, or IV (See Appendix D)
• Subjects with a blood pressure of \>140/90 mmHg. The BP should be taken using the method described in Section 9.3. Subjects taking antihypertensive medications must be taking ≤ 2 medications to obtain this level of BP control.
• Subjects with tumors that are currently involving the lumen of the gastrointestinal tract
• Subjects with current evidence of cardiac ischemia or heart failure within the last 6 months, subjects who are receiving any medications for cardiac ischemia, subjects with a B-type natriuretic peptide (BNP) value of \>200 pg/mL, subjects with a LVEF \< 45%, or subjects that have received a total cumulative dose of ≥400 mg/m2 doxorubicin.
• Subjects with ECG evidence of ischemia or ≥ Grade 2 ventricular arrhythmia, subjects who have a history of acute myocardial infarction within 6 months, or subjects with unstable angina.

Sponsors & Collaborators

• OncoMed Pharmaceuticals, Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (5)

Sydney Cancer Centre

Camperdown, New South Wales, 2050, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Ashford Cancer Centre Research

Kurralta Park, South Australia, 5037, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms; Neoplasm Metastasis

Interventions

demcizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

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

Study Record Dates

• First Submitted: August 25, 2010
• First Posted: August 27, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

AU (4); NZ (1)