NCT02581215

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

Completed Phase 2 Results posted Last updated 1 January 2025

What this trial tests

Phase 2 trial testing mFOLFIRINOX in Pancreatic Cancer in 84 participants. Completed in 27 January 2022.

Timeline

11 September 2016

Primary endpoint
5 August 2021

27 January 2022

Quick facts

Lead sponsor	Walid Shaib, MD
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	84
Start date	11 September 2016
Primary completion	5 August 2021
Estimated completion	27 January 2022
Sites	8 locations across United States

Drugs / interventions tested

• mFOLFIRINOX
• Ramucirumab (RAMUCIRUMAB) — full drug profile →
• Placebo

Conditions studied

• Pancreatic Cancer — all drugs for Pancreatic Cancer →

Sponsor

Walid Shaib, MD

Who can join

18 and older, any sex, with Pancreatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) at 9 Month Primary · 9 months

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.

Group	Value	95% CI
Arm A: Experimental Arm	25.1	11.6 – 41.3
Arm B: Placebo Arm	35	19.8 – 50.6

Overall Survival (OS) Secondary · Up to a maximum of 53 months

Overall survival is defined by the date of randomization to date of death from any cause.

Group	Value	95% CI
Arm A: Experimental Arm	10.3	6 – 11.8
Arm B: Placebo Arm	9.7	6.4 – 15.9

Response Rate (RR) Secondary · Up to 44 months

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. Overall Response (OR) = CR + PR.

Group	Value	95% CI
Arm A: Experimental Arm	17.7
Arm B: Placebo Arm	22.6

Number of Participants With Adverse Events Secondary · From date of first dose until 30 days after the last treatment, assessed up to 44 months

Adverse events will be assessed to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.

Group	Value	95% CI
Arm A: Experimental Arm	42
Arm B: Placebo Arm	40

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality was monitored up to a maximum of 53 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored up to 44 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A: Experimental Arm

Serious: 19/42 (45%)

Deaths: 33/42

Arm B: Placebo Arm

Serious: 17/40 (43%)

Deaths: 35/40

Serious adverse events (41 terms)

Reaction	System	Arm A: Experimental Arm	Arm B: Placebo Arm
DIARRHEA	Gastrointestinal disorders	—	—
DUODENAL OBSTRUCTION	Gastrointestinal disorders	—	—
SEPSIS	Infections and infestations	—	—
VOMITING	Gastrointestinal disorders	—	—
ABDOMINAL PAIN	Gastrointestinal disorders	—	—
BLOOD BILIRUBIN INCREASED	Investigations	—	—
DEHYDRATION	Metabolism and nutrition disorders	—	—
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	—	—
UPPER GASTROINTESTINAL HEMORRHAGE	Gastrointestinal disorders	—	—
ABDOMINAL DISTENSION	Gastrointestinal disorders	—	—
ANOREXIA	Metabolism and nutrition disorders	—	—
CHOLECYSTITIS	Hepatobiliary disorders	—	—
COLITIS	Gastrointestinal disorders	—	—
CONFUSION	Psychiatric disorders	—	—
CONSTIPATION	Gastrointestinal disorders	—	—
DYSPNEA	Respiratory, thoracic and mediastinal disorders	—	—
ENCEPHALOPATHY	Nervous system disorders	—	—
ESOPHAGITIS	Gastrointestinal disorders	—	—
FATIGUE	General disorders	—	—
GASTRITIS	Gastrointestinal disorders	—	—
GASTROINTESTINAL DISORDERS - OTHER, SPECIFY	Gastrointestinal disorders	—	—
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY	General disorders	—	—
GENERALIZED MUSCLE WEAKNESS	Musculoskeletal and connective tissue disorders	—	—
HYPOKALEMIA	Metabolism and nutrition disorders	—	—
HYPOTENSION	Vascular disorders	—	—

Other adverse events (182 terms — click to expand)

Reaction	System	Arm A: Experimental Arm	Arm B: Placebo Arm
DIARRHEA	Gastrointestinal disorders	—	—
NAUSEA	Gastrointestinal disorders	—	—
FATIGUE	General disorders	—	—
WEIGHT LOSS	Investigations	—	—
VOMITING	Gastrointestinal disorders	—	—
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	—	—
ABDOMINAL PAIN	Gastrointestinal disorders	—	—
ANOREXIA	Metabolism and nutrition disorders	—	—
NEUTROPHIL COUNT DECREASED	Investigations	—	—
ANEMIA	Blood and lymphatic system disorders	—	—
HYPOKALEMIA	Metabolism and nutrition disorders	—	—
PLATELET COUNT DECREASED	Investigations	—	—
HYPERTENSION	Vascular disorders	—	—
ALKALINE PHOSPHATASE INCREASED	Investigations	—	—
CONSTIPATION	Gastrointestinal disorders	—	—
ALANINE AMINOTRANSFERASE INCREASED	Investigations	—	—
ANXIETY	Psychiatric disorders	—	—
HYPERGLYCEMIA	Metabolism and nutrition disorders	—	—
HYPONATREMIA	Metabolism and nutrition disorders	—	—
DEHYDRATION	Metabolism and nutrition disorders	—	—
DEPRESSION	Psychiatric disorders	—	—
GASTROESOPHAGEAL REFLUX DISEASE	Gastrointestinal disorders	—	—
HYPOMAGNESEMIA	Metabolism and nutrition disorders	—	—
WHITE BLOOD CELL DECREASED	Investigations	—	—
ALOPECIA	Skin and subcutaneous tissue disorders	—	—
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	—	—
BACK PAIN	Musculoskeletal and connective tissue disorders	—	—
DYSGEUSIA	Nervous system disorders	—	—
DYSPNEA	Respiratory, thoracic and mediastinal disorders	—	—
FEVER	General disorders	—	—
HYPOALBUMINEMIA	Metabolism and nutrition disorders	—	—
THROMBOEMBOLIC EVENT	Vascular disorders	—	—
EDEMA LIMBS	General disorders	—	—
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - OTHER, SPECIFY	General disorders	—	—
HEADACHE	Nervous system disorders	—	—
MUCOSITIS ORAL	Gastrointestinal disorders	—	—
BLOOD BILIRUBIN INCREASED	Investigations	—	—
COUGH	Respiratory, thoracic and mediastinal disorders	—	—
DIZZINESS	Nervous system disorders	—	—
GENERALIZED MUSCLE WEAKNESS	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: DIARRHEA, DUODENAL OBSTRUCTION, SEPSIS, VOMITING, ABDOMINAL PAIN, BLOOD BILIRUBIN INCREASED, DEHYDRATION, FEBRILE NEUTROPENIA.

Data from ClinicalTrials.gov NCT02581215 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Phage Display Derived Monoclonal Antibodies: From Bench to Bedside.
   Alfaleh MA, Alsaab HO, Mahmoud AB, Alkayyal AA, et al · · 2020 · cited 194× · PMID 32983137 · DOI 10.3389/fimmu.2020.01986
2. Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue.
   Longo V, Brunetti O, Gnoni A, Cascinu S, et al · · 2016 · cited 74× · PMID 27462915 · DOI 10.18632/oncotarget.10765
3. The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.
   Garcia-Sampedro A, Gaggia G, Ney A, Mahamed I, et al · · 2021 · cited 31× · PMID 33546207 · DOI 10.3390/jcm10040566
4. Update on the role of nanoliposomal irinotecan in the treatment of metastatic pancreatic cancer.
   Rahman FAU, Ali S, Saif MW. · · 2017 · cited 25× · PMID 28804517 · DOI 10.1177/1756283x17705328
5. Phase II randomised, double-blind study of mFOLFIRINOX plus ramucirumab versus mFOLFIRINOX plus placebo in advanced pancreatic cancer patients (HCRN GI14-198).
   Shaib WL, Manali R, Liu Y, El-Rayes B, et al · · 2023 · cited 10× · PMID 37268519 · DOI 10.1016/j.ejca.2023.02.030
6. Efficacy and safety of gemcitabine plus anti-angiogenesis therapy for advanced pancreatic cancer: a systematic review and meta-analysis of clinical randomized phase III trials.
   Tong M, Wang J, Zhang H, Xing H, et al · · 2019 · cited 8× · PMID 30854103 · DOI 10.7150/jca.26672
7. The Achilles' Heel of Pancreatic Cancer: Targeting pancreatic cancer's unique immunologic characteristics and metabolic dependencies in clinical trials.
   Siolas D, Morrissey C, Oberstein PE. · · 2020 · cited 7× · PMID 33133736 · DOI 10.1097/jp9.0000000000000052
8. Pancreatic Cancer: Pathogenesis and Clinical Studies.
   Zhou K, Liu Y, Tang C, Zhu H. · · 2025 · cited 6× · PMID 40182139 · DOI 10.1002/mco2.70162