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Modified Chemotherapy Alternated with Biweekly Gemcitabine plus Nab-Paclitaxel for the Treatment of Stage IV Pancreatic Cancer

Trial Status: Active

This phase II trial studies how well modified combination chemotherapy alternated with biweekly gemcitabine plus nab-paclitaxel works in treating patients with stage IV pancreatic cancer. Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, oxaliplatin, gemcitabine, and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to examine the effects of two active chemotherapy regiments, modified combination chemotherapy and biweekly gemcitabine plus nab-paclitaxel, administered as a combined, alternating treatments in patients with pancreatic cancer.

Inclusion Criteria

  • Histologically and/or cytologically confirmed pancreatic adenocarcinoma
  • 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
  • Subject must have received no prior therapy for the treatment of metastatic disease. Prior treatment with fluorouracil (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
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Evidence of measurable or nonmeasurable 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
  • 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
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet count >= 100,000/uL
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =< 1.5 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 5 X ULN
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [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
  • Creatinine < 1.5 x institutional ULN or calculated creatinine clearance >= 50 mL/min as estimated using the Cockcroft-Gault formula
  • Partial thromboplastin time (PTT) < 1.2 x ULN and international normalized ratio (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
  • Subject must have no clinically significant abnormalities in urinalysis results (obtained =< 14 days prior to starting cycle 1 day 1)
  • Ability to understand the nature of this study protocol and give written informed consent
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria

  • Ineligible histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas
  • 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
  • Presence of central nervous system metastases
  • Life expectancy < 12 weeks
  • Pregnancy (positive pregnancy test) or lactation
  • Pre-existing sensory neuropathy > grade 1
  • 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
  • Major surgery without complete recovery in the past 4 weeks prior to screening
  • 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
  • Concurrent active infection
  • Patient with uncontrolled and/ or active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
  • Patient who has a history of allergy or hypersensitivity to any of the study drugs
  • Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis
  • Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study

New Jersey

Long Branch
Monmouth Medical Center
Status: ACTIVE
Contact: Seth D. Cohen
Phone: 732-222-1711
New Brunswick
Rutgers Cancer Institute of New Jersey
Status: ACTIVE
Contact: Lyudmyla Berim
Phone: 732-235-6779

PRIMARY OBJECTIVE:

I. To determine whether modified fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) (mFFX) and gemcitabine plus nab-paclitaxel (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.

SECONDARY OBJECTIVES:

I. To determine objective response rate (ORR) of the regimen.

II. To determine progression-free survival (PFS) rate of the regimen.

III. To determine overall survival (OS) rate of the regimen.

IV. To assess biomarker response (CA-19.9) to the regimen.

V. To examine safety and tolerability of the new regimen.

VI. To examine health-related quality of life in patients receiving this regimen.

EXPLORATORY OBJECTIVES:

I. To determine the tumor molecular profile prior to initiation of chemotherapy and correlate with treatment response.

II. To analyze circulating tumor(ct)-deoxyribonucleic acid (DNA) as a biomarker of response to therapy and early detection of disease progression.

OUTLINE:

Patients receive alternating cycles of mFFX (cycles 1, 3, every odd number cycle) and mGnabP (cycles 2, 4, every even number cycle). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

mFFX: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive pegylated-granulocyte colony stimulating factor subcutaneously (SC) on days 3 and 17.

mGnabP: Patients nab-paclitaxel IV over 30 minutes and gemcitabine hydrochloride IV over 120 minutes on day 1 and 15. Patients also receive pegylated-granulocyte colony stimulating factor SC on days 2 and 16.

After completion of study treatment, patients are followed up at 30-60 days and then every 3 months for up to 2 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Rutgers Cancer Institute of New Jersey

Principal Investigator
Lyudmyla Berim

  • Primary ID 072011
  • Secondary IDs NCI-2020-07802, Pro2020002395
  • Clinicaltrials.gov ID NCT04672005