AMG 479 In Advanced Carcinoid And Pancreatic Neuroendocrine Tumors

Study Overview

AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

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.

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

Neuroendocrine Tumor
Carcinoid Tumor
Pancreatic Neuroendocrine Tumor

DRUG: AMG 479

09-240

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2009-12-01	Results First Submitted 2017-11-30	Last Update Submitted that met QC Criteria 2018-02-07
First Submitted that Met QC Criteria 2009-12-01	Results First Submitted that Met QC Criteria 2017-11-30	Last Update Posted (ACTUAL) 2018-03-08
First Posted (ACTUAL) 2009-12-02	Results First Posted 2017-12-27	Last Verified 2018-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: AMG 479 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.	DRUG: AMG 479

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: AMG 479

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.

DRUG: AMG 479

Primary Outcome Measures	Measure Description	Time Frame
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.	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 Measures	Measure Description	Time Frame
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).	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).
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.	Toxicity was evaluated every cycle (3 weeks) on treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).
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.	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.
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.	Patients in this study cohort were followed up to 20 months.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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 ]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Brigham and Women's Hospital
Massachusetts General Hospital
H. Lee Moffitt Cancer Center and Research Institute
Amgen

Investigators

PRINCIPAL_INVESTIGATOR: Matthew Kulke, MD, Dana-Farber Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

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