Clinical trial NCT02318784: Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers
Official title: Phase II Study of Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Cancer
Keywords: neuroendocrine malignancies
pancreatic neuroendocrine tumors (PNETs)
gastrointestinal (GI) carcinoids
carfilzomib
Kyprolis
proteasome inhibitors
Lead sponsor: SCRI Development Innovations, LLC
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2014-12-17
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Adults with biopsy-proven advanced, unresectable or metastatic, well-to-moderately differentiated (or low grade) neuroendocrine carcinoma, including typical carcinoid, pancreatic islet cell and other well-to-moderately differentiated neuroendocrine carcinomas.
2. Measurable disease per Response Evaluation Criteria in Solid Tumors RECIST v 1.1 criteria.
3. Patients currently receiving or previously treated with single agent sandostatin LAR® are eligible. However, this is not a mandatory criterion to be included in the study.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
5. Adequate hematologic, renal, and hepatic function.
6. Predicted life expectancy \> 12 weeks.

Exclusion Criteria:

1. Patients with poorly differentiated neuroendocrine carcinoma, high-grade neuroendocrine carcinoma, adenocarcinoid, globlet cell carcinoid, atypical carcinoid, anaplastic carcinoid, pulmonary neuroendocrine and small cell carcinoma are not eligible.
2. Patients who had radiation therapy, hormonal therapy, biologic therapy, investigational agents, or chemotherapy for cancer within 21 days or 5 half-lives of any chemotherapy or biologic/targeted agent, whichever is longer, prior to first treatment day of the study.
3. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would impair the ability of the patient to receive protocol treatment.
4. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
5. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.
6. Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years
measure: Progression Free Survival (PFS)
timeFrame: up to 4 years
measure: Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
timeFrame: From the day of the first dose to 30 days after the last dose of study medication, up to 4 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North
state: Florida
city: Harvey
country: United States
facility: Ingalls Cancer Research Center
state: Illinois
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Cincinnati
country: United States
facility: Oncology Hematology Care, INC.
state: Ohio
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center/Gibbs Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Fort Worth
country: United States
facility: Center for Cancer and Blood Disorders
state: Texas
Study officials:
affiliation: SCRI Development Innovations, LLC
name: David Spigel, M.D.
role: STUDY_CHAIR
References: