AMG 479 in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors

• ClinicalTrials.gov Identifier: NCT01024387
• Recruitment Status: Completed
• First Posted: December 2, 2009
• Results First Posted: December 27, 2017
• Last Update Posted: March 8, 2018
• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Brigham and Women's Hospital; Massachusetts General Hospital; H. Lee Moffitt Cancer Center and Research Institute; Amgen
• Information provided by (Responsible Party): Matthew H. Kulke, MD, Dana-Farber Cancer Institute

Tracking Information

• First Submitted Date: December 1, 2009
• First Posted Date: December 2, 2009
• Results First Submitted Date: November 30, 2017
• Results First Posted Date: December 27, 2017
• Last Update Posted Date: March 8, 2018
• Actual Study Start Date: March 2010
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2017)

Objective Response Rate [ 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). ]

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.

• Original Primary Outcome Measures (submitted: December 1, 2009): To determine the objective response rate associated with AMG 479 in patients with advanced carcinoid or pancreatic neuroendocrine tumors. [ Time Frame: 2 years ]

Current Secondary Outcome Measures (submitted: November 30, 2017)

• Duration of Response [ 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). ]
  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 [ 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). ]
  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 [ 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. ]
  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 [ Time Frame: Patients in this study cohort were followed up to 20 months. ]
  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.

Original Secondary Outcome Measures (submitted: December 1, 2009)

• To determine the duration of response associated with AMG 479 in this patient population. [ Time Frame: 4 years ]
• To determine the safety and tolerability of AMG 479 in this patient population. [ Time Frame: 2 years ]
• To determine the progression free survival and overall survival of carcinoid or pancreatic neuroendocrine tumor patients receiving AMG 479. [ Time Frame: 4 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Neuroendocrine Tumor
• Carcinoid Tumor
• Pancreatic Neuroendocrine Tumor

Intervention

Drug: AMG 479

Other Name: ganitumab

Study Arms

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.

Intervention: Drug: AMG 479

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 1, 2009): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2017
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

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 ]

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01024387
• Other Study ID Numbers: 09-240
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Matthew H. Kulke, MD, Dana-Farber Cancer Institute
• Study Sponsor: Dana-Farber Cancer Institute

Collaborators

• 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

• PRS Account: Dana-Farber Cancer Institute
• Verification Date: February 2018