Study of Abituzumab in Combination With Cetuximab and FOLFIRI in Patients With Metastatic Colorectal Cancer.

NCT03688230 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: AP2187972018-003439-31AIO-KRK-0318/ass
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of the experimental drug abituzumab (EMD525797) in combination with cetuximab and FOLFIRI in RAS wild-type, left-sided, metastatic colorectal cancer patients with high ανβ6 integrin expression.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression free survival per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.

  16 months

Secondary Outcomes (6)

• Overall Survival (OS)

  68 months

• Objective Response Rate (ORR)

  16 months

• Depth of Response (DPR)

  16 months

• Early Tumor Shrinkage (ETS)

  68 months

• Secondary Resection Rate With a Potentially Curative Intent

  16 months

Study Arms (2)

Abituzumab + Cetuximab + FOLFIRI

EXPERIMENTAL

Cetuximab: 400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min * (60 min \[± 5 min\] after completion of the cetuximab infusion) Abituzumab 1000 mg: every 2 weeks for 60 min * (60 min \[± 5 min\] after completion of the abituzumab infusion) FOLFIRI: every 2 weeks Irinotecan 180 mg/m² IV, 30 - 90 min day 1 Folinic acid (racemic) 400 mg/m² IV, 120 min day 1 5-FU 400 mg/m² bolus day 1 5-FU 2400 mg/m² IV over a period of 46 h day 1-2

Drug: abituzumab

Placebo + Cetuximab + FOLFIRI

PLACEBO COMPARATOR

Cetuximab: 400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min * (60 min \[± 5 min\] after completion of the cetuximab infusion) Placebo: every 2 weeks for 60 min * (60 min \[± 5 min\] after completion of the placebo infusion) FOLFIRI: every 2 weeks Irinotecan 180 mg/m² IV, 30 - 90 min day 1 Folinic acid (racemic) 400 mg/m² IV, 120 min day 1 5-FU 400 mg/m² bolus day 1 5-FU 2400 mg/m² IV over a period of 46 h day 1-2

Combination Product: Placebo + Cetuximab + FOLFIRI

Interventions

abituzumab DRUG

1000 mg IV

Also known as: EMD525797

Abituzumab + Cetuximab + FOLFIRI

Placebo + Cetuximab + FOLFIRI COMBINATION_PRODUCT

400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min

Placebo + Cetuximab + FOLFIRI

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent prior to any study specific procedure;
• Age: ≥18 years;
• Evidence of newly diagnosed stage IV metastatic colorectal cancer. Primary tumor location on the left side of the Colon (including left splenic flexure) or rectum;
• Demonstrated wild-type RAS mutation status in the tumor (primary tumor or metastasis) by local assessment;
• Tumor tissue specimen shows high ανβ6 integrin expression, as determined by central laboratory assessment;
• Tumor tissue specimen (formalin-fixed, paraffin-embedded block) preferably from primary resection and/or if available from a surgical sample from metastatic site must be available for central laboratory based ανβ6 integrin expression analysis. (No Fine Needle Aspiration \[FNA\] will be accepted);
• At least 1 radiographically documented measurable lesion in a previously non-irradiated area according to RECIST (Version 1.1), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as ≥2 cm by conventional techniques or ≥1 cm by spiral CT scan;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;
• Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study;

You may not qualify if:

• Demonstrated any RAS or BRAF mutation;
• Prior anti-EGFR or other targeted therapy;
• Prior chemotherapy of the colorectal cancer, except for (neo) adjuvant therapy completed at least 6 months before randomization;
• Radiotherapy (localized radiotherapy for pain relief is allowed to non-target lesions);
• Investigational drug treatment for the treatment of malignancies in the past;
• Concurrent participation in another interventional clinical study;
• Any history or evidence of brain metastases or leptomeningeal metastases;
• History of secondary malignancy within the past 5 years, except for basal cell carcinoma or carcinoma in situ of the cervix uteri, if treated with curative intent;
• Concomitant chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement; steroids up to 10 mg per day of prednisone equivalent or topical and inhaled steroids are allowed);
• Clinically relevant coronary artery disease (New York Heart Association \[NYHA\] functional angina classification III/IV), congestive heart failure (NYHA III/IV), or clinically relevant cardiomyopathy;
• Uncontrolled hypertension defined as systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg under resting conditions;
• History of myocardial infarction in the last 12 months, or a high risk of uncontrolled arrhythmia, coagulation disorder associated with bleeding or recurrent thrombotic events, with the exception of arterial fibrillation treated with anti-coagulants;
• Recent peptic ulcer disease (endoscopically proven) within 6 months of randomization, chronic inflammatory bowel disease, or acute/chronic ileus;
• Active infection (requiring IV antibiotics and/or antiviral therapy), including active tuberculosis, active or chronic Hepatitis B or C, or ongoing HIV infection, AIDS;
• Presence of any contra-indications or known hypersensitivity to treatment with abituzumab, cetuximab, and FOLFIRI, or to any of the excipients of these drugs;

Sponsors & Collaborators

• SFJ Pharmaceuticals X, LTD.: lead
• SFJ Pharmaceuticals, Inc.: collaborator
• Merck KGaA, Darmstadt, Germany: collaborator
• AIO-Studien-gGmbH: collaborator
• Academic and Community Cancer Research United: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Abituzumab; Cetuximab

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

Study Officials

• Dirk Arnold, Prof. Dr.

  Asklepios Tumorzentrum Hamburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: September 28, 2018
• Study Start: April 1, 2019
• Primary Completion: December 1, 2020
• Study Completion: August 1, 2021
• Last Updated: March 18, 2020

Record last verified: 2020-03