Modified FOLFIRINOX Alternated With Biweekly Gemcitabine Plus Nab-Paclitaxel Untreated Pancreatic Cancer

Modified FOLFIRINOX Alternated With Biweekly Gemcitabine Plus Nab-Paclitaxel in Untreated Metastatic Adenocarcinoma of the Pancreas

The main objective of the clinical trial is to determine if modified FOLFIRINOX (mFFX) alternated with biweekly Gemcitabine plus Nab-Paclitaxel (mGnabP) administered as a combined, front-line therapy will result in longer time to treatment failure (TTF) compared to the current standard of care with mFFX alone in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (PDAC).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Pancreatic Cancer
• Intervention / Treatment: Drug: Folfirinox alternating with Gemcitabine-nab-Paclitaxel

Detailed Description

1. Primary objective:

   To determine whether mFFX and mGnabP administered as a combined, alternating, front-line therapy can provide longer first line treatment for patients with metastatic pancreatic cancer, with the primary metric of time to treatment failure (TTF), including progression of disease (PD), death or treatment discontinuation due to toxicity.

   • Primary endpoint: TTF (treatment discontinuation due to toxicity, disease progression, or death).

2. Secondary objectives:

1) To determine objective response rate (ORR) of the regimen. 2) To determine progression-free survival (PFS) rate of the regimen. 3) To determine overall survival (OS) rate of the regimen. 4) To assess biomarker response (CA-19.9) to the regimen. 5) To examine safety and tolerability of the new regimen. 6) To examine health-related quality of life in patients receiving this regimen.

• Secondary endpoints:

1. ORR as determined by the proportion of subjects with either complete response (CR) or partial response (PR), as defined by RECIST 1.1.
2. PFS as determined by the time interval from the date of first dose of study regimen to first documented PD or death from any cause, whichever occurs first.
3. Overall survival (OS) as defined as the time interval from the date of the first dose of study regimen to date of death from any cause.
4. Biomarker response, measured by serum CA 19-9 levels every 4 weeks.
5. Safety and tolerability of the mFFX alternating with mGnabP regimen; Grade 3 and 4 toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Follow up for toxicity will be recorded for the first 30 days following the last chemotherapy cycle, and any long-term toxicity will be followed for up to 2 years after completion of study therapy.

3. Exploratory objectives:

1. To determine the tumor molecular profile prior to initiation of chemotherapy and correlate with treatment response.
2. To analyze ct-DNA as a biomarker of response to therapy and early detection of disease progression.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lyudmyla Berim, MD; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu

Study Locations

• United States
  • New Jersey
    • Hamilton, New Jersey, United States, 08690
      • Recruiting
      • RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton
      • Contact: Lyudmyla Berim; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu
    • Jersey City, New Jersey, United States, 07302
      • Recruiting
      • RWJBarnabas Health - Jersey City Medical Center, Jersey City
      • Contact: Lyudmyla Berim; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu
    • Livingston, New Jersey, United States, 07039
      • Recruiting
      • RWJBarnabas Health - Saint Barnabas Medical Center, Livingston
      • Contact: Lyudmyla Berim; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu
    • Long Branch, New Jersey, United States, 07740
      • Recruiting
      • Monmouth Medical Center
      • Contact: Seth Cohen, MD; Phone Number: 732-222-1711
    • New Brunswick, New Jersey, United States, 08903
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
      • Contact: Lyudmila Berim, MD; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu
      • Principal Investigator: Lyudmila Berim, MD
    • Newark, New Jersey, United States, 07112
      • Recruiting
      • RWJBarnabas Health - Newark Beth Israel Medical Center
      • Contact: Lyudmyla Berim; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu
    • Somerset, New Jersey, United States, 08873
      • Recruiting
      • RWJBarnabas Health - Robert Wood Johnson University Hospital, Somerset
      • Contact: Lyudmyla Berim; Phone Number: 732-235-6779; Email: lb830@cinj.rutgers.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically and/or cytologically confirmed pancreatic adenocarcinoma.
2. Stage IV disease. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data.
3. Subject must have received no prior therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed. If a subject received prior neoadjuvant or adjuvant chemotherapy, tumor recurrence must have occurred more than 6 months after completing the last dose of chemotherapy.
4. ECOG performance status of 0-1.
5. At least 18 years of age.
6. Evidence of measurable or non-measurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Tumors within a previously irradiated field will be designated as "nontarget" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy.
7. Female patients of childbearing potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male and female patients must agree to use effective barrier contraception during the period of therapy.
8. Adequate bone marrow function:

8a. ANC ≥ 1500/uL 8b.platelet count ≥ 100,000/uL 8c. hemoglobin ≥ 9.0 g/dL 9. Adequate hepatic function: 9a. Total bilirubin ≤ 1.5 X ULN 9b. AST (SGOT) ≤ 5 X ULN 9c. ALT (SGPT) ≤ 5 X ULN Patients with biliary obstruction must have restored biliary flow by placement of an endoscopic common bile duct stent or a percutaneous drainage.

10. Adequate renal function, Creatinine < 1.5x institutional ULN or calculated creatinine clearance ≥ 50 mL/min as estimated using the Cockcroft-Gault formula.

11. Partial thromboplastin time (PTT) < 1.2 x ULN and INR ≤ 1.5 x ULN, if not receiving anticoagulation therapy. For patients receiving anticoagulants, exceptions to these coagulation parameters are allowed if they are within the intended or expected range for their therapeutic use.

12. Subject must have no clinically significant abnormalities in urinalysis results (obtained ≤ 14 days prior to starting Cycle 1 Day 1).

13. Ability to understand the nature of this study protocol and give written informed consent. 14. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

Patients who meet any one of the following criteria will be excluded from this study.

1. Ineligible histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas.
2. Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
3. Presence of central nervous system metastases.
4. Life expectancy < 12 weeks.
5. Pregnancy (positive pregnancy test) or lactation.
6. Pre-existing sensory neuropathy > grade 1.
7. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.
8. Major surgery without complete recovery in the past 4 weeks prior to screening.
9. Prior malignancy except for adequately treated basal cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other form of cancer from which the patient has been disease-free for 5 years.
10. Concurrent active infection.
11. Patient with uncontrolled and/ or active infection with HIV, Hepatitis B or Hepatitis C.
12. Patient who has a history of allergy or hypersensitivity to any of the study drugs.
13. Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis.
14. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Regimen: mFOLFIRINOX + mGnabP; All study participants will receive the following treatment: mFOLFIRINOX (28-day cycle) Day 1 and Day 15: Oxaliplatin 85 mg/m2 2-hour intravenous infusion followed by leucovorin 400 mg/m2 2-hour infusions with the addition of irinotecan 150 mg/m2 as a 90 minute infusion. 5-FU 2400 mg/m2 continuous intravenous infusion over 46 hours will follow irinotecan. Day 3 and Day 17: Pegylated-Granulocyte Colony Stimulating Facotr (peg-GCSF) 6 mg subcutaneous injection following disconnection of 5-FU infusion, first cycle and then per investigator discretion. Biweekly mGnabP (28-day cycle) Day 1 and Day 15: Nab-paclitaxel 125 mg/m2 infused over 30 minutes, immediately followed by Gemcitabine 1200 mg/m2 intravenously infused at the rate of 10mg/m2/min (over 120 minutes). Patients will receive one month of each regimen, alternately monthly until progression of disease.

Drug: Folfirinox alternating with Gemcitabine-nab-Paclitaxel; modified Folfirinox every 2 weeks and biweekly Gemcitabine plus Nab-Paclitaxel; Other Names: Gemcitabine; Leucovorin; Irinotecan; Oxaliplatin; Nab-Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to treatment failure (TTF)	The primary objective of this study is to determine time to treatment failure (TTF) in patients with metastatic pancreatic cancer treated in front line setting with mFOLFIRINOX (mFFX) alternating with biweekly Gemcitabine and nab-Paclitaxel (mGnabP).	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Evaluation Criteria in Solid Tumors (RECIST 1.1	Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1 by independent radiology review) at 8 week intervals.	24 weeks
Progression-free survival (PFS)	To determine progression-free survival (PFS) rate of the regimen.	24 weeks
Overall survival (OS)	To determine overall survival (OS) rate of the regimen.	24 weeks
Safety and tolerability assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0	4. Safety and tolerability of the mFFX alternating with mGnabP regimen; Grade 3 and 4 toxicities will be assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Follow up for toxicity will be recorded for the first 30 days following the last chemotherapy cycle, and any long-term toxicity will be followed for up to 2 years after completion of study therapy.	24 weeks
EORTC QLQ-CIPN20 questionnaire	Patient reported outcomes, examined through the EORTC QLQ-CIPN20 questionnaire	Administered at baseline prior to start of therapy, then every 8 weeks while receiving therapy, and at the end of treatment, average of 1 year
Correlation between variation in variant allele fraction (% cfDNA) or amplifications and tumor objective response during chemotherapy	Correlation between variation in the variant allele fraction (% cfDNA) or amplifications and tumor objective response during chemotherapy	Assessed at baseline prior to therapy, every 8 weeks interval through duration of therapy, and at end of treatment, average 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between variation of ctDNA and progression free survival	Correlation between variation of ctDNA and progression free survival	24 weeks

Collaborators and Investigators

• Sponsor: Lyudmyla Berim
• Investigators: Principal Investigator: Lyudmyla Berim, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Paclitaxel; Oxaliplatin; Leucovorin; Irinotecan; Albumin-Bound Paclitaxel; Folfirinox; Gemcitabine
• Other Study ID Numbers: Pro2020002395; 072011 (Other Identifier: Rutgers Cancer Institute of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No