Georgia's Online Cancer Information Center

Find A Clinical Trial

Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients with Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer

Status
Closed
Cancer Type
Colon/Rectal Cancer
Trial Phase
Phase I
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT03337087
Protocol IDs
ACCRU-GI-1603 (primary)
NCI-2017-01976
Study Sponsor
Academic and Community Cancer Research United

Summary

This phase I/II trial studies the side effects and best dose of liposomal irinotecan and rucaparib when given together with fluorouracil and leucovorin calcium and to see how well they work in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as liposomal irinotecan, fluorouracil, and leucovorin calcium, 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. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as rucaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving liposomal irinotecan and rucaparib together with fluorouracil and leucovorin calcium may work better in treating patients with pancreatic, colorectal, gastroesophageal, or biliary cancer.

Objectives

PRIMARY OBJECTIVES:
I. To establish the recommended dose level for the phase Ib and phase II trial of liposomal irinotecan (nal-IRI) and fluorouracil (5-FU) with rucaparib (MFR) in patients with metastatic disease from pancreatic cancer (up to 2 lines of prior therapy), colorectal cancer (up to 3 lines of prior therapy), gastroesophageal cancer (up to 1 line of prior therapy) and biliary tract cancer (with 1 line of prior therapy allowed). (Phase I)
II. To assess, in a preliminary fashion, antitumor efficacy, in terms of disease control rate and further tolerability, of the recommended dose level of combination of nal-IRI and 5-FU with rucaparib in patients with metastatic disease from pancreatic cancer (=< 1 line of prior therapy in the metastatic setting). (Phase Ib)
III. To estimate the proportion of evaluable patients who reach complete response (CR)/partial response (PR) =< 32 weeks after registration among patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1, BRCA2, and PALB2 mutation, treated with the combination of nal-IRI and 5FU with rucaparib (MFR). (Phase II)

SECONDARY OBJECTIVES:
I. To estimate the progression-free survival (PFS) and overall survival (OS) for patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1, BRCA2, and PALB2 mutation, treated with the combination of nal-IRI and 5-FU with rucaparib (MFR). (Phase II)
II. To assess the toxicity of the combination of nal-IRI and 5-FU with rucaparib in patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD), specifically BRCA1/2 and PALB2 mutations. (Phase II)

EXPLORATORY OBJECTIVES:
I. To evaluate the role of genomic markers (signature) of HRD, mutation other than BRCA1, BRCA2, and PALB2 as predictive biomarkers of response to MFR.
II. To evaluate BRCA1, BRCA2, and PALB2 mutations as predictive biomarker of response to MFR.

OUTLINE: This is phase I, dose-escalation study of liposomal irinotecan and rucaparib and followed by a phase II study.

PHASE Ia: Patients receive liposomal irinotecan intravenously (IV) over 90 minutes, leucovorin calcium IV, and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib orally (PO) twice daily (BID) on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.

PHASE Ib/II: Patients receive liposomal irinotecan IV over 90 minutes and fluorouracil IV over 46 hours on days 1 and 15. Patients also receive rucaparib PO BID on days 4-13 and 18-27. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Eligibility

  1. Phase I only: Histologic confirmation of pancreatic, colorectal, gastroesophageal or biliary adenocarcinoma, as follows: * Patients with metastatic disease from pancreatic cancer who received no more than 2 lines of prior therapy in the metastatic setting * Patients with metastatic disease from colorectal cancer who received no more than 3 lines of prior therapy in the metastatic setting * Patients with metastatic disease from gastroesophageal cancer who received no more than 1 line of prior therapy in the metastatic setting * Patients with metastatic disease from biliary tract cancer who received no more than 1 line of prior therapy in the metastatic setting * NOTE: No prior exposure to irinotecan in the metastatic setting will be allowed except in the phase I dose escalation portion and in colon cancer patients only; in pancreas cancer, exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
  2. Phase Ib only: Patients with metastatic adenocarcinoma of the pancreas who have who received no more than 1 line of prior therapy in the metastatic setting * NOTE: Exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
  3. Phase II only: Patients with metastatic adenocarcinoma of the pancreas with genomic markers (signature) of homologous recombination deficiency (HRD) or BRCA1 or BRCA2 or PALB2 mutation, or HRD (non-BRCA, non-PALB) who have not received any systemic therapy in the metastatic setting * NOTE: Exposure to irinotecan is only allowed in the neoadjuvant setting and no progressive disease < 3 months from last dose of irinotecan
  4. Measurable disease
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  6. Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 21 days prior to registration)
  7. Platelet count >= 100,000/mm^3 (obtained =< 21 days prior to registration)
  8. Hemoglobin > 9.0 g/dL (obtained =< 21 days prior to registration)
  9. Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 21 days prior to registration)
  10. Aspartate transaminase (AST) =< 3 x ULN, =< 5.0 x ULN for patients with metastatic disease to the liver (obtained =< 21 days prior to registration)
  11. Aminotransferase (ALT) =< 3.0 x ULN, =< 5.0 x ULN for patients with metastatic disease to the liver (obtained =< 21 days prior to registration)
  12. Creatinine =< 1.0 mg/dL or creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 21 days prior to registration)
  13. Negative serum or urine pregnancy test done =< 7 days prior to registration and repeated prior to dosing on day 1 of each cycle, for individuals of childbearing potential only; NOTE: Individuals are considered to be of childbearing potential unless one of the following applies: * Is postmenopausal, defined as no menses for at least 12 months without an alternative medical cause; a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state: or * Considered to be permanently sterile; permanent sterilization includes hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy
  14. Provide informed written consent
  15. Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study) * Note: During the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  16. Willing to provide tissue and blood samples for mandatory correlative research purposes
  17. Individuals of reproductive potential and their partners willing to practice total abstinence or use a highly effective method of contraception (failure rate < 1% per year) during treatment and for 6 months following the last dose of rucaparib; the following are allowable only: * Ongoing use of progesterone-only injectable or implantable contraceptives (eg, Depo Provera, Implanon, Nexplanon) * Placement of an intrauterine device or intrauterine system * Bilateral tubal occlusion * Sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate * True, complete (as opposed to periodic) abstinence
  18. Patients must discontinue prior chemotherapy >= 28 days before registration

Treatment Sites in Georgia

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
Georgia CORE

 

Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.