Open Label Extension Study of Conatumumab and Ganitumab (AMG 479)

A Phase 2 Open Label Extension Study of Conatumumab and AMG 479

The purpose of this protocol is to allow continued treatment with conatumumab and/or ganitumab, with or without chemotherapy, to participants who completed a separate Amgen-sponsored conatumumab or ganitumab study without disease progression whose previous studies were closed.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Lymphoma; Colorectal Cancer; Non-Small Cell Lung Cancer; Advanced Solid Tumors; Metastatic Cancer; Solid Tumors; Carcinoid; Locally Advanced
• Intervention / Treatment: Biological: Conatumumab; Biological: Ganitumab; Drug: Modified FOLFOX6; Biological: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Szczecin, Poland, 70-891
    • Research Site
• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
• United States
  • California
    • Duarte, California, United States, 91010
      • Research Site
    • La Jolla, California, United States, 92093-0957
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80218
      • Research Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • New York
    • Buffalo, New York, United States, 14263
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Utah
    • Ogden, Utah, United States, 84403
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• To be enrolled in this study, subjects must be currently enrolled in a prior Amgen-sponsored conatumumab or AMG 479 study and are eligible according to the parent study to receive their next dose of conatumumab (with or without co-therapy), or AMG 479 alone.

Subjects must have their eligibility assessed for this study and be enrolled within 30 days of their last treatment on the parent protocol

Exclusion Criteria:

• Discontinued from a conatumumab study due to an adverse event considered by the investigator to be related to conatumumab treatment, including intolerance to conatumumab
• Subjects determined to have disease progression during their participation in the parent Amgen study
• Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last dose of protocol-specified therapy administration
• Subject is pregnant or breast feeding, or planning to become pregnant within 6 months after the last dose of protocol-specified therapy administration
• Male subject with a pregnant partner who is not willing to use a condom during treatment and for an additional 6 months after the last dose of protocol-specified therapy administration
• Subject has previously entered this study
• Subject will not be available for protocol required study visits, to the best of the subject and investigator's knowledge
• Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conatumumab Monotherapy; Participants will continue to receive conatumumab every 2 weeks (Q2W) or every 3 weeks (Q3W) at the same dose and regimen as at the conclusion of the parent study.	Biological: Conatumumab; Administered by intravenous infusion Q2W or Q3W.; Other Names: AMG 655
Experimental: Conatumumab + Ganitumab; Participants will receive conatumumab and ganitumab by intravenous infusion at the same dose and regimen as at the conclusion of the parent study.	Biological: Conatumumab; Administered by intravenous infusion Q2W or Q3W.; Other Names: AMG 655; Biological: Ganitumab; Administered by intravenous infusion Q3W or Q4W.; Other Names: AMG 479
Experimental: Ganitumab Monotherapy; Participants will continue to receive ganitumab Q3W or every 4 weeks (Q4W) at the same dose and regimen as at the conclusion of the parent study.	Biological: Ganitumab; Administered by intravenous infusion Q3W or Q4W.; Other Names: AMG 479
Experimental: Conatumumab + mFOLFOX6 ± Bevacizumab; Participants will continue to receive conatumumab by intravenous infusion in addition to modified FOLFOX6 chemotherapy with or without bevacizumab.	Biological: Conatumumab; Administered by intravenous infusion Q2W or Q3W.; Other Names: AMG 655; Drug: Modified FOLFOX6; The mFOLFOX6 regimen is a combination therapy of oxaliplatin 85 mg/m² administered as a 2-hour intravenous (IV) infusion on day 1 and leucovorin 400 mg/m² racemate or 200 mg/m² levo-leucovorin administered as a 2-hour infusion on day 1, followed by a loading dose of 5-fluorouracil (5-FU) 400 mg/m² IV bolus administered on day 1, then 5-FU 2400 mg/m² via ambulatory pump administered for a period of 46 to 48 hours every 14 days.; Other Names: Oxaliplatin-Leucovorin-Fluorouracil chemotherapy; Biological: Bevacizumab; Administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle.; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	An adverse event is defined as any untoward medical occurrence in a clinical trial participant, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment.	From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
Number of Participants With Serious Adverse Events	A serious adverse event is defined as an adverse event that met at least 1 of the following serious criteria: fatal,; life threatening (places the participant at immediate risk of death),; required in-patient hospitalization or prolongation of existing hospitalization,; resulted in persistent or significant disability/incapacity,; congenital anomaly/birth defect, and/or; other medically important serious event.	From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Change From Baseline in Blood Pressure	Maximum change from baseline is defined for each participant as the maximum change from baseline value observed across all visits.	Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
Minimum Change From Baseline in Blood Pressure	Minimum change from baseline is defined for each participant as the minimum change from baseline value observed across all visits.	Baseline and day 1 of each treatment cycle (every 2, 3, or 4 weeks depending on dosing schedule) up to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
Number of Participants With CTCAE Grade 3 or Higher Clinical Laboratory Toxicities	Laboratory toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.	From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
Best Overall Response	Radiological assessments to evaluate disease extent (with change compared to nadir from the parent protocol) were performed at regular intervals, at a minimum once every 6 months or more frequently if clinically indicated (starting from their last scan on the parent protocol), per standard of care (SOC) at each facility. Tumor response was assessed by the Investigator as either complete response, partial response, stable disease, or progressive disease.	Approximately every 6 months until end of treatment; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.
Number of Participants With Disease Progression or Death Due to Disease Progression		From first dose of study drug in the extension study to 30 days after last dose; median duration of treatment with conatumumab was 1190.5 days and 1163.0 days for ganitumab.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2011
• Primary Completion (Actual): February 5, 2020
• Study Completion (Actual): February 5, 2020

Study Registration Dates

• First Submitted: March 3, 2011
• First Submitted That Met QC Criteria: March 31, 2011
• First Posted (Estimate): April 1, 2011

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 3, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Bevacizumab; Lymphoma; Monoclonal Antibody; FOLFOX; AMG 479; Tumor Necrosis Factor; Apoptosis; AMG 655; Insulin-like Growth Factor; mFOLFOX6; Modified FOLFOX6; Trail Receptor; ganitumab; conatumumab
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Neuroendocrine Tumors; Neoplasms; Neoplasm Metastasis; Carcinoid Tumor; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Bevacizumab; Leucovorin; Conatumumab
• Other Study ID Numbers: 20101116; 2010-022270-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR