Alternating Chemotherapy Regimens (FOLFOX and FOLFIRI) for the Treatment of Metastatic Pancreatic Cancer in Older Patients
This phase II trial tests the safety and side effects of alternating chemotherapy regimens, leucovorin, fluorouracil and oxaliplatin (FOLFOX) and leucovorin, fluorouracil, and irinotecan (FOLFIRI) in treating older patients with pancreatic cancer that has spread to other places in the body (metastatic). Chemotherapy drugs such as leucovorin, fluorouracil, oxaliplatin, and irinotecan 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. Giving FOLFOX and FOLFIRI on an alternating schedule, whereby two of the drugs are given at a time rather than all 3, and switching off every other cycle, may minimize side effects and maintain the effect on the cancer.
Inclusion Criteria
- Age 65 years or older
- The treating physician will use their discretion when assessing if the patient is eligible for this treatment
- Patients must have newly diagnosed and previously untreated, histologically or cytologically confirmed adenocarcinoma of the pancreas, with at least one site of metastatic disease (local recurrences after surgery allowed), with lesions that are measurable by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. In patients with mixed histology tumors, the predominant feature must be adenocarcinoma
- Eastern Cooperative Oncology Group Performance status of 0-2
- Previous surgery, adjuvant chemotherapy and/or radiation therapy will be allowed, provided radiation therapy is completed at least 2 weeks prior to signing consent and adjuvant therapy was administered more than 6 months prior to signing consent
- Absolute Neutrophil Count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< 2 X upper limit of normal (ULN)
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT)/alkaline phosphatase =< 3 X ULN or =< 5 X ULN if liver metastasis present
- Creatinine =< 2.0 mg/dL
- Estimated glomerular filtration rate (eGFR) (using Cockcroft Gault equation) > 40ml/min
- Patients must be fluent in English or Spanish and must be able and willing to undergo Comprehensive Geriatric Assessment. Patients who are Spanish-speaking can be enrolled if an interpreter is available to conduct the baseline geriatric assessment
- Chemotherapy is harmful to the human fetus. For this reason, sexually active males with partners of childbearing potential must agree to use an accepted and effective method of contraception prior to study entry and for the duration of the study
- Patients must demonstrate ability to understand and the willingness to sign a written informed consent document
- Men and women, regardless of race, ethnic group or sexual orientation are eligible for this study
Exclusion Criteria
- Endocrine or acinar pancreatic carcinoma
- Patients who have had any systemic chemotherapy in the metastatic or locally advanced inoperable setting (adjuvant or neoadjuvant therapy is allowed)
- Patients who have received radiation therapy within 2 weeks of signing consent
- Patients who are currently receiving or have previously received any other investigational therapy for metastatic pancreatic cancer
- Patients with known brain metastases – treated or untreated, are excluded from this study because of their poor prognosis and frequent development of progressive neurological dysfunction that would confound the evaluation of neurologic and other adverse events
- Any patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Patients with untreated and active human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection are not eligible for this trial.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active bacterial infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with evidence of active malignancy within 2 years of enrollment without definitive treatment. Patients with localized prostate cancer status-post surgical resection or definitive radiation, localized estrogen receptor (ER)/progesterone receptor positive (PR+)/HER2 negative (-) breast cancer status-post definitive local treatment with a low OncotypeDx (registered trademark) on adjuvant hormonal therapy, or local skin cancers that were previously resected will be eligible for inclusion. Patients with a history of in situ cancers treated with definitive local therapy will also be eligible
- Patients with grade 3 or higher baseline sensory neuropathy
- Patients with chronic diarrhea (> 4 bowel movements/day) unresolved despite best supportive care for greater than 2 weeks
- Patients with any of the following documented criteria: * > 2 falls in the past month * Body mass index (BMI) =<18
Additional locations may be listed on ClinicalTrials.gov for NCT05360732.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To assess the toxicity profile of a regimen of alternating FOLFOX and FOLFIRI at 2 months in newly diagnosed and untreated metastatic pancreatic adenocarcinoma patients over the age of 65 years deemed ineligible to receive the leucovorin, 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) regimen.
SECONDARY OBJECTIVE:
I. To assess the progression free survival (PFS), overall survival (OS), objective response rate (ORR) and delayed toxicities (> 2 months) of newly diagnosed and untreated metastatic pancreatic adenocarcinoma patients over the age of 65 deemed ineligible for FOLFIRINOX, treated with alternating FOLFOX and FOLFIRI.
EXPLORATORY OBJECTIVES:
I. Explore the ability of geriatric assessment variables to predict for grade 3 or higher adverse events among newly diagnosed and untreated metastatic pancreatic cancer patients over the age of 65 years treated with alternating regimen of FOLFOX and FOLFIRI (aFOLFOXIRI).
II. To evaluate the association between pre-treatment levels of biomarkers of aging (IL6, c-reactive protein [CRP], D-Dimer), and grades of toxicities with alternating FOLFOX and FOLFIRI chemotherapy.
III. Explore the ability of activity level (Fitbit recording) to predict for grade 3 or higher adverse events among newly diagnosed and untreated metastatic pancreatic cancer patients over the age of 65 years treated with aFOLFOXIRI.
IV. Assess quality of life measures of treatment in all patients treated with aFOLFOXIRI.
V. Correlation of physician determined performance status and objectively determined activity level (through Fitbit Charge [Trademark]).
OUTLINE:
Patients receive FOLFOX regimen consisting of the following: 1) oxaliplatin intravenously (IV) over 120 minutes on day 1 of each cycle, 2) leucovorin IV over 120 minutes on day 1 of each cycle, and 3) 5-fluorouracil IV continuous infusion over 46-48 hours on day 1 of each cycle. Patients also receive FOLFIRI regimen consisting of the following: 1) irinotecan IV over 90 minutes on day 14 of each cycle, 2) leucovorin IV over 90 minutes on day 14 of each cycle, and 5-fluorouracil IV continuous infusion over 46-48 hours on day 14 of each cycle. Cycles repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) every eight weeks during the first 6 cycles and then every eight to twelve weeks thereafter.
After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 24 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationFox Chase Cancer Center
Principal InvestigatorDina Ioffe
- Primary ID20-1027
- Secondary IDsNCI-2022-05648, GI-170
- ClinicalTrials.gov IDNCT05360732