Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin

Brief summary public domain (ClinicalTrials.gov)

This phase II trial studies how well liposomal irinotecan, leucovorin, and fluorouracil work in treating patients with high grade neuroendocrine cancer of gastrointestinal, unknown, or pancreatic origin that does not respond to treatment and has spread to other places in the body. Lliposomal irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin, 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 liposomal irinotecan, leucovorin and fluorouracil may work better in treating patients with neuroendocrine cancer.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: I. To determine the objective response rate liposomal irinotecan (nanoliposomal irinotecan \[Nal-IRI\]) + fluorouracil (5FU) and leucovorin in patients with refractory advanced high grade neuroendocrine cancer of gastrointestinal (GI), unknown or pancreatic origin. SECONDARY OBJECTIVES: I. To determine overall survival, progression-free survival, time to treatment failure, safety, clinical response and, quality of life (QOL) changes resulting from the combination treatment of nanoliposomal irinotecan (Nal-IRI) + fluorouracil (5FU) and leucovorin. EXPLORATORY OBJECTIVES: I. Genetic profiling for mutations will be conducted on all pre-study tumor samples and compared to changes in immune response. OUTLINE: Patients receive liposomal irinotecan intravenously (IV) over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days, then every 2 months thereafter.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Within 6 months of treatment initiation]. Count Of Participants, Participants. Objective Response (CR+PR): Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=9): 1. No Objective Response (SD+PD): Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=9): 8. Analysis, Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil): Proportion 0.091 (80% CI 0.033 to 0.301); other.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Overall Survival [From first dosing of study treatment combination to time of death or imitation of a new therapy, assessed up to 3 years]. Median, months (95% Confidence Interval). Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 8.3 (2.3 to 18.2).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Progression-free Survival Assessed by RECIST 1.1 [From first dosing of study treatment combination to disease progression, assessed up to 3 years]. Median, months (95% Confidence Interval). Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 3.9 (0.5 to 5.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Time-to Treatment Failure [From enrollment to discontinuation of treatment, assessed up to 3 years]. Median, months (90% Confidence Interval). Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 3.9 (1.7 to 4.4).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Proportion of Patients Achieving an Objective Response Based on Prior Response to Platinum Etoposide [Up to 3 years]. Count Of Participants, Participants. No Objective Response: Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=4): 3. Objective Response: Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=4): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Clinical Benefit Response [Up to 3 years].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Quality of Life (QOL) as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) [From treatment initiation until treatment completion/progression (up to 3 years).]. Mean, units on a scale (Standard Deviation). Pre Treatment QoL: Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 5.9 (1.4). End of Treatment QoL: Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 5.5 (1.7). Analysis, Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil): p=0.289; Sign test; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Incidence of Grade 3+ Treatment Related Adverse Events (TRAE) [Up to 3 years]. Count Of Participants, Participants. No Grade 3+ TRAE: Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 4. Grade 3+ TRAE: Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) (n=11): 7.