Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Carcinoma, Neuroendocrine

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Carcinoid Tumor

Carcinoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Proteasome Inhibitors

Carfilzomib will be administered as intravenous (IV) infusion over 30 minutes on Days 1, 2, 8, 9, 15 and 16 of each 28-day cycle.

Cycle 1: First two doses of Carfilzomib 20 mg/m2 IV; subsequent doses at 56 mg/m2 IV

Cycle 2 onwards: Carfilzomib 56 mg/m2 IV

Carfilzomib

David Spigel, M.D.

The purpose of this study is to determine if carfilzomib is safe and effective in the treatment of patients with advanced neuroendocrine tumors.

Neuroendocrine malignancies such as pancreatic neuroendocrine tumors (PNETs) and gastrointestinal (GI) carcinoids, are generally rare but their incidences are increasing. In vitro and in vivo studies have shown that proteasome inhibitors have activity against a variety of tumor types. Carfilzomib (Kyprolis®) is an irreversible proteasome inhibitor with a favorable safety profile that has been studied in a variety of hematologic and solid tumors. Carfilzomib received accelerated approval from the U.S. FDA in 2012, based on a favorable response rate, for the treatment of patients with multiple myeloma who received at least two prior therapies, and demonstrated disease progression within 60 days of completing the last therapy. In this multi-center study, the investigators propose to evaluate carfilzomib for the treatment of patients with advanced neuroendocrine cancers.

Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers

Phase II Study of Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers

Percentage of participants with confirmed complete response (CR) or partial response (PR) (i.e. 2 CRs or PRs at least 4 weeks apart) to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) CR=disappearance of all target lesions. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) (≥ 6 cycles) according to RECIST v1.1 criteria. Complete Response is defined per RECIST as the disappearance of all target/non-target lesions and normalization of tumor markers. Partial Response is defined per RECIST as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable disease is defined per RECIST as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (nadir) sum LD since the treatment started.

Measured from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on the study. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions. Patients who did not have disease progression or death documented were censored on the date of the last visit with adequate assessment.

The number of treatment-emergent adverse events will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03

Amgen

SCRI Development Innovations, LLC

All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from the day of the first dose to 30 days after the last dose of the study medication and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Carfilzomib - administered as an intravenous (IV) infusion over 30 minutes on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.

Cycle 1: First two doses of Carfilzomib 20 mg/m\^2 IV; subsequent doses at 56 mg/m2 IV

Cycle 2 onwards: Carfilzomib 56 mg/m\^2 IV

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Full analysis set - all enrolled patients who receive at least one full or partial dose of the study group and who have measurable disease at baseline

Sarah Cannon Development Innovations, LLC

All enrolled patients who received at least one full or partial dose of the study drug and who had measurable disease at baseline were included in the analysis.

Overall Response Rate (ORR)

Disease Control Rate (DCR)

Progression Free Survival (PFS)

All enrolled patients who received at least one full or partial dose of the study drug.

Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability

Overall Study

Antineoplastic Agents

Temozolomide

Lenograstim

Mitogens

Antimetabolites

Antineoplastic Agents, Alkylating

Alkylating Agents

Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.

Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.

TAS-102

Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Filgrastim

Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Pegfilgrastim

Nataliya Uboha, MD

The goal of this study is to establish maximum tolerated doses/recommended phase 2 dose (RP2D) of temozolomide (TMZ) and TAS-102 when these agents are used in combination and to evaluate the safety profile of this drug combination.

The study is a two part phase 1B clinical trial consisting of three study periods: a screening period of 14 days or less, a treatment period, and a safety follow-up period 30 days after treatment discontinuation.

Part 1 is a dose finding phase with the objective to assess the safety and tolerability of the proposed drug combination and to identify the maximum tolerated dose (MTD) and a recommended phase 2 dose.

Part 2 is an open-label expansion study, which will enroll patients with metastatic pNETs who have not been previously treated with chemotherapy. Part 2 will obtain further safety data of the proposed drug combination.

Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs

Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic Neuroendocrine Tumors

Investigate the safety and determine the MTD of TAS-102 administered in combination with TMZ in patients with advanced NETs. Treatments will continue to disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST).

Response rate defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR), assessed as per RECIST criteria. Assessments performed using RECIST criteria.

Defined as the time from the start of treatment to the date of first documented progression or any cause of death during the study, assessed according to RECIST. Analyzed using the Kaplan-Meier method.

Defined as the time from the start of treatment to the date of expiration. Analyzed using the Kaplan-Meier method.

Defined as the percentage of patients who achieved complete response, partial response, and stable disease by investigator assessment as per RECIST.

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

A major biochemical response will be defined as normalization or \>50% reduction in levels of Chromogranin A. Chromogranin A is elevated in up to 60% of functioning and nonfunctioning pancreatic endocrine tumors.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers	NCT02318784	Neuroendocrine ...	Carfilzomib	18 Years -	SCRI Development Innovations, LLC
Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs	NCT02943733	Neuroendocrine ... Neoplasms Cancer Tumors	TAS-102 Temozolomide Filgrastim Pegfilgrastim	18 Years -	University of Wisconsin, Madison
Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs	NCT02943733	Neuroendocrine ... Neoplasms Cancer Tumors	TAS-102 Temozolomide Filgrastim Pegfilgrastim	18 Years -	University of Wisconsin, Madison

Spots Global Cancer Trial Database for pancreatic neuroendocrine tumors (pnets)