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AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

Primary Purpose

Neuroendocrine Tumor, Carcinoid Tumor, Pancreatic Neuroendocrine Tumor

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AMG 479
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroendocrine Tumor focused on measuring AMG 479

Eligibility Criteria

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

Inclusion Criteria:

  • Locally unresectable or metastatic carcinoid or pancreatic neuroendocrine tumors. To be classified as having a pancreatic neuroendocrine tumor, patients must have clinical evidence of currently having or having had a primary pancreatic neuroendocrine lesion.
  • Measurable disease by RECIST criteria
  • Evidence of progressive disease (by RECIST) within 12 months of study entry.
  • Tumors must be considered well- or moderately-differentiated. Patients with poorly differentiated neuroendocrine carcinoma of small cell carcinoma are excluded from this study.
  • Adequate hepatic, renal, bone marrow and glycemic function as outlined in the protocol
  • Prior treatment with chemotherapy, hepatic artery embolization, surgery or other therapeutic agents is allowed.
  • Prior or concurrent therapy with somatostatin analogs is permitted: however patients must continue on a stable dose of somatostatin analogs while receiving study treatment.
  • 18 years of age or older
  • ECOG performance status 0, 1, or 2 [Eastern Cooperative Oncology Group ]
  • Life expectancy of at least 12 weeks
  • Negative pregnancy test
  • Ability to sign informed consent

Exclusion Criteria:

  • Poorly differentiated or small cell neuroendocrine carcinomas
  • Insulin secreting pancreatic neuroendocrine tumors (insulinomas)
  • Clinically apparent central nervous system metastases or carcinomatous meningitis.
  • Myocardial infraction in the past 6 months
  • Major surgery 4 weeks prior to enrollment
  • Uncontrolled serious medical or psychiatric illness
  • Pregnant or lactating women. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study.
  • Prior antitumor therapy within 4 weeks of enrollment (with the exception of somatostatin analogs).
  • Recent infection requiring systemic anti-infective treatment that was completed 14 days or less prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection).
  • Known positive test for human immunodeficiency virus, hepatitis C, chronic or active hepatitis B
  • Prior IGF or IGF receptor inhibitor therapy [insulin like growth factor ]

Sites / Locations

  • H. Lee Moffitt Cancer Center
  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AMG 479

Arm Description

Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.

Outcomes

Primary Outcome Measures

Objective Response Rate
Objective response rate is the percentage of patients achieving partial response (PR) or complete response (CR) per RECIST 1.0 criteria. For target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR status must be confirmed by repeat assessments performed no fewer than 4 weeks or more than 6 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Secondary Outcome Measures

Duration of Response
The duration of response is measured from the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Grade 3-4 Toxicity Rate
Grade 3-4 toxicity rate is the percentage of patients who experienced a grade 3 or 4 adverse event with treatment attribution of possible, probable or definite based on CTCAEv4.
Progression Free Survival
Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the time from the start of treatment to the date of the first documented disease progression or death due to any cause. Patients without an event were censored at the earliest date of last disease assessment or initiation of non-protocol anti-cancer therapy. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
1-Year Overall Survival
Overall survival (OS) based on the Kaplan-Meier method is defined as the time from treatment start to the date of death or censored at the date last known alive. 1-year overall survival is the probability (%) of remaining alive 1 year from the start of treatment.

Full Information

First Posted
December 1, 2009
Last Updated
February 7, 2018
Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Massachusetts General Hospital, H. Lee Moffitt Cancer Center and Research Institute, Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT01024387
Brief Title
AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors
Official Title
A Multi-Institutional, Phase II Open-Label Study of AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
March 2010 (Actual)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Massachusetts General Hospital, H. Lee Moffitt Cancer Center and Research Institute, Amgen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this research study is to determine the effectiveness of AMG 479 against carcinoid and pancreatic neuroendocrine tumors. AMG 479 is an antibody that is made in the laboratory. Antibodies are highly specific proteins produced by the body's immune system that recognize foreign substances in the body. AMG 479 has been used in other research studies and information from those other research studies suggests that AMG 479 may help to prevent the growth of some neuroendocrine tumors. The observed antitumor activity of AMG 479, together with the current limited treatment options available for patients with neuroendocrine tumors, warrant further investigation of AMG 479 in this patient population.
Detailed Description
Neuroendocrine tumors (NETs) comprise a heterogeneous spectrum of neoplasms. NETs are commonly subclassified into two broad subgroups according to their site of origin: pancreatic NETs are thought to arise from the endocrine cells of the pancreas, whereas NETs of other sites such as the lungs or gastrointestinal tract are often referred to as carcinoid tumors. While histologically similar, carcinoid tumors and pancreatic neuroendocrine tumors have demonstrated different response rates in prior phase II studies of antitumor agents. Because of these differences, we will perform the current study using two cohorts of patients (30 with carcinoid and 30 with pancreatic neuroendocrine tumors). The statistical design, however, is the same for both cohorts. With 30 patients in each cohort, this study has 80% power assuming type I error of 6% to differentiate a >/=17% objective response rate from a </=5% objective response rate using a single stage design. The proposed regimen would be promising in either cohort if at least 4 of 30 patients achieve an objective response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumor, Carcinoid Tumor, Pancreatic Neuroendocrine Tumor
Keywords
AMG 479

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
AMG 479
Arm Type
Experimental
Arm Description
Patients receive AMG 479 at a dose of 18 mg/kg administered IV on day 1 (± 3 days) of every 3-week cycle. Treatment should continue until disease progression, unacceptable toxicity or withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
AMG 479
Other Intervention Name(s)
ganitumab
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
Objective response rate is the percentage of patients achieving partial response (PR) or complete response (CR) per RECIST 1.0 criteria. For target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR status must be confirmed by repeat assessments performed no fewer than 4 weeks or more than 6 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame
Disease was evaluated radiologically at baseline, every 3 cycles (9 weeks) on treatment and at end of treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).
Secondary Outcome Measure Information:
Title
Duration of Response
Description
The duration of response is measured from the time measurement criteria are met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time Frame
Disease was evaluated radiologically at baseline, every 3 cycles (9 weeks) on treatment and at end of treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).
Title
Grade 3-4 Toxicity Rate
Description
Grade 3-4 toxicity rate is the percentage of patients who experienced a grade 3 or 4 adverse event with treatment attribution of possible, probable or definite based on CTCAEv4.
Time Frame
Toxicity was evaluated every cycle (3 weeks) on treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).
Title
Progression Free Survival
Description
Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the time from the start of treatment to the date of the first documented disease progression or death due to any cause. Patients without an event were censored at the earliest date of last disease assessment or initiation of non-protocol anti-cancer therapy. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time Frame
Disease was evaluated radiologically at baseline, every 3 cycles (9 weeks) on treatment and at end of treatment. Patients in this study cohort were followed up to 20 months.
Title
1-Year Overall Survival
Description
Overall survival (OS) based on the Kaplan-Meier method is defined as the time from treatment start to the date of death or censored at the date last known alive. 1-year overall survival is the probability (%) of remaining alive 1 year from the start of treatment.
Time Frame
Patients in this study cohort were followed up to 20 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Locally unresectable or metastatic carcinoid or pancreatic neuroendocrine tumors. To be classified as having a pancreatic neuroendocrine tumor, patients must have clinical evidence of currently having or having had a primary pancreatic neuroendocrine lesion. Measurable disease by RECIST criteria Evidence of progressive disease (by RECIST) within 12 months of study entry. Tumors must be considered well- or moderately-differentiated. Patients with poorly differentiated neuroendocrine carcinoma of small cell carcinoma are excluded from this study. Adequate hepatic, renal, bone marrow and glycemic function as outlined in the protocol Prior treatment with chemotherapy, hepatic artery embolization, surgery or other therapeutic agents is allowed. Prior or concurrent therapy with somatostatin analogs is permitted: however patients must continue on a stable dose of somatostatin analogs while receiving study treatment. 18 years of age or older ECOG performance status 0, 1, or 2 [Eastern Cooperative Oncology Group ] Life expectancy of at least 12 weeks Negative pregnancy test Ability to sign informed consent Exclusion Criteria: Poorly differentiated or small cell neuroendocrine carcinomas Insulin secreting pancreatic neuroendocrine tumors (insulinomas) Clinically apparent central nervous system metastases or carcinomatous meningitis. Myocardial infraction in the past 6 months Major surgery 4 weeks prior to enrollment Uncontrolled serious medical or psychiatric illness Pregnant or lactating women. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study. Prior antitumor therapy within 4 weeks of enrollment (with the exception of somatostatin analogs). Recent infection requiring systemic anti-infective treatment that was completed 14 days or less prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection). Known positive test for human immunodeficiency virus, hepatitis C, chronic or active hepatitis B Prior IGF or IGF receptor inhibitor therapy [insulin like growth factor ]
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Kulke, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23572164
Citation
Strosberg JR, Chan JA, Ryan DP, Meyerhardt JA, Fuchs CS, Abrams T, Regan E, Brady R, Weber J, Campos T, Kvols LK, Kulke MH. A multi-institutional, phase II open-label study of ganitumab (AMG 479) in advanced carcinoid and pancreatic neuroendocrine tumors. Endocr Relat Cancer. 2013 May 21;20(3):383-90. doi: 10.1530/ERC-12-0390. Print 2013 Jun.
Results Reference
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AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

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