Clinical trial NCT01024387: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumor
Carcinoid Tumor
Pancreatic Neuroendocrine Tumor
Keywords: AMG 479
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
name: H. Lee Moffitt Cancer Center and Research Institute
name: Amgen
First posted: 2009-12-02
Enrollment: 60
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 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.

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 \[insulin like growth factor \]

Primary outcomes:
measure: Objective Response Rate
timeFrame: 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 outcomes:
measure: Duration of Response
timeFrame: 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).
measure: Grade 3-4 Toxicity Rate
timeFrame: Toxicity was evaluated every cycle (3 weeks) on treatment. Patients in this study cohort received a median of 6 treatment cycles (18 weeks).
measure: Progression Free Survival
timeFrame: 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.
measure: 1-Year Overall Survival
timeFrame: Patients in this study cohort were followed up to 20 months.
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Matthew Kulke, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.