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

NCT ID: NCT03688230

Last Updated: 2020-03-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-30
• Study Completion Date: 2021-08-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Abituzumab + Cetuximab + FOLFIRI

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

Group Type: EXPERIMENTAL

abituzumab

Intervention Type: DRUG

1000 mg IV

Placebo + Cetuximab + FOLFIRI

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

Group Type: PLACEBO_COMPARATOR

Placebo + Cetuximab + FOLFIRI

Intervention Type: 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

Interventions

abituzumab

1000 mg IV

Intervention Type: DRUG

Placebo + Cetuximab + FOLFIRI

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

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

EMD525797

Eligibility Criteria

Inclusion Criteria

1. Signed and dated written informed consent prior to any study specific procedure;

2. Age: ≥18 years;

3. 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;

4. Demonstrated wild-type RAS mutation status in the tumor (primary tumor or metastasis) by local assessment;

5. Tumor tissue specimen shows high ανβ6 integrin expression, as determined by central laboratory assessment;

6. 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);

7. 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;

8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;

9. Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study;

Exclusion Criteria

1. Demonstrated any RAS or BRAF mutation;

2. Prior anti-EGFR or other targeted therapy;

3. Prior chemotherapy of the colorectal cancer, except for (neo) adjuvant therapy completed at least 6 months before randomization;

4. Radiotherapy (localized radiotherapy for pain relief is allowed to non-target lesions);

5. Investigational drug treatment for the treatment of malignancies in the past;

6. Concurrent participation in another interventional clinical study;

7. Pregnancy (exclusion confirmed with beta-hCG test) or lactation;

8. Any history or evidence of brain metastases or leptomeningeal metastases;

9. 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;

10. 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);

11. 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;

12. Uncontrolled hypertension defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg under resting conditions;

13. 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;

14. Recent peptic ulcer disease (endoscopically proven) within 6 months of randomization, chronic inflammatory bowel disease, or acute/chronic ileus;

15. Active infection (requiring IV antibiotics and/or antiviral therapy), including active tuberculosis, active or chronic Hepatitis B or C, or ongoing HIV infection, AIDS;

16. Presence of any contra-indications or known hypersensitivity to treatment with abituzumab, cetuximab, and FOLFIRI, or to any of the excipients of these drugs;

17. Concomitant treatment with prohibited medications;

18. Medical or psychological conditions that would not permit the patient to complete the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SFJ Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

AIO-Studien-gGmbH

OTHER

Sponsor Role: collaborator

Academic and Community Cancer Research United

OTHER

Sponsor Role: collaborator

SFJ Pharmaceuticals X, LTD.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dirk Arnold, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Asklepios Tumorzentrum Hamburg

Other Identifiers

2018-003439-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AIO-KRK-0318/ass

Identifier Type: OTHER

Identifier Source: secondary_id

AP218797

Identifier Type: -

Identifier Source: org_study_id