Phase II Randomized Trial of mFOLFIRINOX +/- Ramucirumab in Advanced Pancreatic Cancer

NCT02581215 | Completed Phase 2 Results DMC

• 1 other identifier: HCRN GI14-198
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 8

Brief Summary

This is a phase II, multicenter, double-blinded, randomized, 2-arm trial evaluating the efficacy and safety of mFOLFIRINOX plus ramucirumab (Arm A) vs. mFOLFIRINOX plus placebo (Arm B) in 94 subjects with advanced pancreatic cancer, not amenable to curative treatment. Both arms will continue treatment until disease progression or unacceptable toxicity.

Conditions

Pancreatic Cancer

Keywords

mFOLFIRINOX; Ramucirumab

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) at 9 Month

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time of registration until disease progression met by RECIST 1.1 or death from any cause.

  9 months

Secondary Outcomes (3)

• Overall Survival (OS)

  Up to a maximum of 53 months

• Response Rate (RR)

  Up to 44 months

• Number of Participants With Adverse Events

  From date of first dose until 30 days after the last treatment, assessed up to 44 months

Study Arms (2)

Arm A: Experimental Arm

EXPERIMENTAL

mFOLFIRINOX will be administered every 2 weeks, and consist of: * Oxaliplatin 85 mg/m2 over 2-4 hours * Irinotecan 165 mg/m2 over 90 minutes * 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia. * Arm A will receive ramucirumab administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.

Drug: mFOLFIRINOX; Drug: Ramucirumab

Arm B: Placebo Arm

PLACEBO COMPARATOR

mFOLFIRINOX will be administered every 2 weeks, and consist of: * Oxaliplatin 85 mg/m2 over 2-4 hours * Irinotecan 165 mg/m2 over 90 minutes * 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia. * Arm B will receive a placebo infusion every 2 weeks. Due to the double-blinded nature of this study, the volume of placebo will be calculated as if it were ramucirumab

Drug: mFOLFIRINOX; Other: Placebo

Interventions

mFOLFIRINOX DRUG

mFOLFIRINOX: * Oxaliplatin 85 mg/m2 over 2-4 hours * Irinotecan 165 mg/m2 over 90 minutes * 5-FU 2,400 mg/m2 as a 46-hour continuous infusion without the 5-FU bolus to decrease the risk of neutropenia.

Arm A: Experimental Arm; Arm B: Placebo Arm

Ramucirumab DRUG

Ramucirumab administered as an intravenous infusion over 60 minutes (infusion rate should not exceed 25 mg/min), at a fixed dose of 8 mg/kg every 2 weeks.

Also known as: Cyramza

Arm A: Experimental Arm

Placebo OTHER

Placebo infusion with volume calculated as if it were ramucirumab every 2 weeks.

Arm B: Placebo Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. .
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 within 7 days prior to registration.
• Histologic or cytological diagnosis of recurrent or metastatic pancreas adenocarcinoma (PCA) who present for first line chemotherapy treatment.
• No prior first line systemic treatment (prior adjuvant or neoadjuvant treatment is permitted). Subjects whose disease has progressed after 6 months of last systemic chemotherapy or chemo-radiation in the adjuvant or neoadjuvant setting are eligible.
• Measurable disease determined using guidelines of Response Evaluation Criteria In Solid Tumors (RECIST 1.1). Baseline tumor assessment should be performed using high resolution computed tomography (CT) scans or magnetic resonance imaging (MRI).
• Urine protein \< 1+ on dipstick test or routine urinalysis. If the proteinuria on these tests is ≥2+, then a 24-hour urine test must be collected and must demonstrate \< 1g proteins in 24 hours to allow participation.
• Estimated life expectancy of \>12 weeks, as assessed by the site investigator.
• If sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods) due to unknown risk of teratogenicity of ramucirumab

You may not qualify if:

• Subjects with histology other than adenocarcinoma; Examples include: neuroendocrine tumors, acinar cell cancer, sarcoma or lymphoma of the pancreas.
• Ongoing or active infection.
• Symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia. Symptomatic heart failure per New York Heart Association (NYHA) Class II-IV.
• Uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management.
• Acute or sub-acute intestinal obstruction.
• Interstitial pneumonia or interstitial fibrosis of the lung, which in the opinion of the site investigator could compromise the subject or the study.
• Pleural effusion or ascites that causes \> grade 1 dyspnea.
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) with a history of hepatic encephalopathy or clinical meaningful ascites resulting from cirrhosis; clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis.
• Grade 3 or higher bleeding event ≤ 3 months prior to randomization.
• Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, ≤ 6 months prior to randomization.
• History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to randomization.
• Documented and/or symptomatic or known brain or leptomeningeal metastases.
• GI perforation/fistula
• Documented and/or symptomatic or known brain or leptomeningeal metastases.
• Severely immune-compromised (other than being on steroids), including known HIV infection.

Sponsors & Collaborators

• Walid Shaib, MD: lead
• Eli Lilly and Company: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (8)

Mayo Clinic-Arizona

Scottsdale, Arizona, 85259, United States

Location

Emory University: Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Community Healthcare System

Munster, Indiana, 46321, United States

Location

University of Louisville, James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Thomas Jefferson University Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Shaib WL, Manali R, Liu Y, El-Rayes B, Loehrer P, O'Neil B, Cohen S, Khair T, Robin E, Huyck T, Bekaii-Saab T. Phase II randomised, double-blind study of mFOLFIRINOX plus ramucirumab versus mFOLFIRINOX plus placebo in advanced pancreatic cancer patients (HCRN GI14-198). Eur J Cancer. 2023 Aug;189:112847. doi: 10.1016/j.ejca.2023.02.030. Epub 2023 Mar 11.

  PMID: 37268519 DERIVED

Related Links

• Hoosier Cancer Research Network Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Ramucirumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

317-921-2050

Study Officials

• Walid Shaib, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Site pharmacy staff will be unblinded to the study treatment. Subjects, site investigators, site analysis teams, and other site personnel will be blinded to the study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: October 20, 2015
• Study Start: September 11, 2016
• Primary Completion: August 5, 2021
• Study Completion: January 27, 2022
• Last Updated: January 1, 2025
• Results First Posted: January 1, 2025

Record last verified: 2024-12

Locations

US (8)