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

Phase 2

Withdrawn

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: abituzumab; Combination Product: Placebo + Cetuximab + FOLFIRI

• Registration Number: NCT03688230
• Lead Sponsor: SFJ Pharmaceuticals X, LTD.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-24
• Study First Submitted QC: 2018-09-26
• Study First Posted: 2018-09-28
• Study Start: 2019-04
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-16
• Last Update Posted: 2020-03-18
• Primary Completion: 2020-12
• Study Completion: 2021-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Abituzumab + Cetuximab + FOLFIRI	abituzumab	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
Placebo + Cetuximab + FOLFIRI	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

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	16 months	Progression free survival per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	68 months	The overall survival is defined as the time from randomization to death from any cause.
Objective Response Rate (ORR)	16 months	ORR will be estimated as the proportion of responders in each treatment arm, defined as a patient whose best overall response is PR or better during the treatment period according to RECIST 1.1.
Depth of Response (DPR)	16 months	Depth of response will be estimated as the maximum percent tumor shrinkage during treatment.
Early Tumor Shrinkage (ETS)	68 months	ETS will be estimated as the proportion of patients achieving a ≥20 % decrease from baseline in the sum of longest tumor diameters.
Secondary Resection Rate With a Potentially Curative Intent	16 months	Patients for whom the resectability of metastases becomes evident during the study therapy should undergo a surgical resection of the metastases.
Number of participants with treatment-related adverse events summarized by CTCAE severity grade (v5.0).	68 months	Adverse events will be summarized by body system, preferred term, severity, and relationship to treatment