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

• ClinicalTrials.gov Identifier: NCT04672005
• Recruitment Status: Recruiting
• First Posted: December 17, 2020
• Last Update Posted: June 10, 2021
• Sponsor: Lyudmyla Berim
• Information provided by (Responsible Party): Lyudmyla Berim, Rutgers, The State University of New Jersey

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Metastatic Pancreatic Cancer	Drug: Folfirinox alternating with Gemcitabine-nab-Paclitaxel	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: single group assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Modified FOLFIRINOX Alternated With Biweekly Gemcitabine Plus Nab-Paclitaxel in Untreated Metastatic Adenocarcinoma of the Pancreas
• Actual Study Start Date: January 6, 2021
• Estimated Primary Completion Date: June 1, 2024
• Estimated Study Completion Date: June 1, 2024

Arms and Interventions

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: Oxaliplatin; Leucovorin; Irinotecan; Nab-Paclitaxel; Gemcitabine

Outcome Measures

Primary Outcome Measures :

1. Time to treatment failure (TTF) [ Time Frame: 24 weeks ]
   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).

Secondary Outcome Measures :

1. Response Evaluation Criteria in Solid Tumors (RECIST 1.1 [ Time Frame: 24 weeks ]
   Response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1 by independent radiology review) at 8 week intervals.
2. Progression-free survival (PFS) [ Time Frame: 24 weeks ]
   To determine progression-free survival (PFS) rate of the regimen.
3. Overall survival (OS) [ Time Frame: 24 weeks ]
   To determine overall survival (OS) rate of the regimen.
4. Safety and tolerability assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [ Time Frame: 24 weeks ]
   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.
5. EORTC QLQ-CIPN20 questionnaire [ Time Frame: 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 ]
   Patient reported outcomes, examined through the EORTC QLQ-CIPN20 questionnaire
6. Correlation between variation in variant allele fraction (% cfDNA) or amplifications and tumor objective response during chemotherapy [ Time Frame: Assessed at baseline prior to therapy, every 8 weeks interval through duration of therapy, and at end of treatment, average 1 year ]
   Correlation between variation in the variant allele fraction (% cfDNA) or amplifications and tumor objective response during chemotherapy

Other Outcome Measures:

1. Correlation between variation of ctDNA and progression free survival [ Time Frame: 24 weeks ]
   Correlation between variation of ctDNA and progression free survival

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Lyudmyla Berim, MD; 732-235-6779; lb830@cinj.rutgers.edu

Locations

United States, New Jersey

Monmouth Medical Center; Recruiting

Long Branch, New Jersey, United States, 07740

Contact: Seth Cohen, MD 732-222-1711

Rutgers Cancer Institute of New Jersey; Recruiting

New Brunswick, New Jersey, United States, 08903

Contact: Lyudmila Berim, MD 732-235-6779 lb830@cinj.rutgers.edu

Principal Investigator: Lyudmila Berim, MD

Sponsors and Collaborators

Lyudmyla Berim

Investigators

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

More Information

• Responsible Party: Lyudmyla Berim, Assistant Professor of Medicine, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT04672005
• Other Study ID Numbers: Pro2020002395; 072011 ( Other Identifier: Rutgers Cancer Institute of New Jersey )
• First Posted: December 17, 2020
• Last Update Posted: June 10, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Leucovorin; Gemcitabine; Paclitaxel; Albumin-Bound Paclitaxel; Oxaliplatin; Irinotecan; Folfirinox; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Topoisomerase I Inhibitors