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Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers

Primary Purpose

Neuroendocrine Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carfilzomib
Sponsored by
SCRI Development Innovations, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Cancer focused on measuring neuroendocrine malignancies, pancreatic neuroendocrine tumors (PNETs), gastrointestinal (GI) carcinoids, carfilzomib, Kyprolis, proteasome inhibitors

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Rocky Mountain Cancer Center
  • Florida Cancer Specialists
  • Florida Hospital Cancer Institute
  • Florida Cancer Specialists - North
  • Ingalls Cancer Research Center
  • Research Medical Center
  • Oncology Hematology Care, INC.
  • Spartanburg Regional Medical Center/Gibbs Cancer Center
  • Tennessee Oncology PLLC
  • Center for Cancer and Blood Disorders

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Carfilzomib

Arm Description

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

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
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.

Secondary Outcome Measures

Disease Control Rate (DCR)
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.
Progression Free Survival (PFS)
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.
Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
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

Full Information

First Posted
December 12, 2014
Last Updated
June 7, 2022
Sponsor
SCRI Development Innovations, LLC
Collaborators
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT02318784
Brief Title
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

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
July 15, 2015 (Actual)
Primary Completion Date
May 15, 2021 (Actual)
Study Completion Date
May 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SCRI Development Innovations, LLC
Collaborators
Amgen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Cancer
Keywords
neuroendocrine malignancies, pancreatic neuroendocrine tumors (PNETs), gastrointestinal (GI) carcinoids, carfilzomib, Kyprolis, proteasome inhibitors

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Carfilzomib
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years
Secondary Outcome Measure Information:
Title
Disease Control Rate (DCR)
Description
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.
Time Frame
every 3 cycles (1 cycle= 28 days) until treatment discontinuation up to 4 years
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
up to 4 years
Title
Number of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability
Description
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
Time Frame
From the day of the first dose to 30 days after the last dose of study medication, up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Measurable disease per Response Evaluation Criteria in Solid Tumors RECIST v 1.1 criteria. 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. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. Adequate hematologic, renal, and hepatic function. Predicted life expectancy > 12 weeks. Exclusion Criteria: 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. 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. 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. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. 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. Known diagnosis of human immunodeficiency virus, hepatitis B or hepatitis C.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Spigel, M.D.
Organizational Affiliation
SCRI Development Innovations, LLC
Official's Role
Study Chair
Facility Information:
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Florida Cancer Specialists
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33916
Country
United States
Facility Name
Florida Hospital Cancer Institute
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Florida Cancer Specialists - North
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
Facility Name
Ingalls Cancer Research Center
City
Harvey
State/Province
Illinois
ZIP/Postal Code
60426
Country
United States
Facility Name
Research Medical Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64132
Country
United States
Facility Name
Oncology Hematology Care, INC.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Spartanburg Regional Medical Center/Gibbs Cancer Center
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
Tennessee Oncology PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Center for Cancer and Blood Disorders
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States

12. IPD Sharing Statement

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Carfilzomib for the Treatment of Patients With Advanced Neuroendocrine Cancers

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