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AMG 386 Phase 2 Open-Label Renal Cell Carcinoma (RCC) Study 1st Line or After Cytokine Failure in Combination With Sunitinib

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00853372
First received: February 26, 2009
Last updated: September 5, 2016
Last verified: August 2016
  Purpose
This phase 2 study is an open-label, multi-center study to determine the safety and tolerability of AMG 386 in combination with sunitinib in the treatment of subjects with metastatic renal cell carcinoma.

Condition Intervention Phase
Advanced Renal Cell Carcinoma
Drug: Sunitinib
Drug: AMG386
Drug: AMG 386
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Open-Label, Multi-Center Study to Evaluate the Safety and Efficacy of Sunitinib Malate in Combination With AMG 386 as First Line or Second Line Therapy for Subjects With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Safety and tolerability of AMG 386 in combination with Sunitinib in subjects with metastatic renal cell carcinoma. [ Time Frame: The primary endpoint is safety and tolerability, as measured by the incidence of adverse events, dose interruptions due to adverse events, dose reductions of sunitinib during the first 12 weeks of study treatment and significant laboratory abnormalities. ] [ Designated as safety issue: No ]
    Incidence of adverse events, dose interruptions due to adverse events, dose reductions of sunitinib during the first 12 weeks of study treatment and significant laboratory abnormalities


Secondary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    The incidence of either a confirmed complete response (CR) or partial response (PR) per modified RECIST criteria (responder). A confirmed CR requires 2 consecutive assessments of CR at least 28 days apart. A confirmed PR requires 2 consecutive assessments at least 28 days apart of PR or CR. All subjects that do not meet the criteria for an objective response by the analysis cutoff date will be considered non responders.

  • Duration of response (DOR) [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Duration of response (DOR) (calculated only for subjects who had an objective response): The time from first confirmed objective response to disease progression or death due to any cause. Subjects not meeting criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date.

  • Disease Control Rate (DCR) [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Defined as the percentage of subjects with confirmed CR or PR or have stable disease (SD), as defined by modified RECIST (CRs or PRs will be confirmed at least 28 days after the criteria for response are first met).

  • Progression Free Survival (PFS) [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    The time from enrollment date to date of disease progression (ie, radiographic progression) per the modified RECIST criteria or death. Subjects not meeting criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. Radiological imaging to assess disease status will be performed until subjects develop disease progression. Events of radiographic progression per RECIST 1.0 with modifications that occur after initiation of subsequent anticancer therapy will not be considered PFS events. Deaths occurring after initiation of subsequent anticancer therapy will be considered PFS events. Further details on events and censoring times of PFS are provided in the Statistical Analysis Plan.

  • Overall Survival (OS) [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    The time from enrollment date to date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.

  • Change in continuous measures of tumor burden [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Change in continuous measures of tumor burden

  • Pharmacokinetic parameters (Cmax and Cmin) for AMG 386 [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters (Cmax and Cmin) for AMG 386 when used in combination with sunitinib

  • Pharmacokinetic parameter (Cmin) for sunitinib and its primary active metabolite [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (Cmin) for sunitinib and its primary active metabolite when used in combination with AMG 386 in a sub-group of subjects at selected sites outside of Europe

  • Incidence of the occurrence of anti-AMG 386 antibody formation [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Incidence of the occurrence of anti-AMG 386 antibody formation


Other Outcome Measures:
  • Baseline values of and changes from baseline in pharmacodynamic markers as assessed by blood levels of angiogenic cytokines (eg VEGF, PIGF, ANG-1, ANG-2) and tumor apoptosis and other markers [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Baseline values of and changes from baseline in pharmacodynamic markers as assessed by blood levels of angiogenic cytokines (eg VEGF, PIGF, ANG-1, ANG-2) and tumor apoptosis and other markers

  • Baseline values of and changes from baseline in immunologic, biochemical and pharmacogenomic markers in tumor biopsies or blood samples [ Time Frame: 48 months after LSE ] [ Designated as safety issue: No ]
    Baseline values of and changes from baseline in immunologic, biochemical and pharmacogenomic markers in tumor biopsies or blood samples


Enrollment: 85
Study Start Date: May 2009
Estimated Study Completion Date: March 2017
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMG 386 10mg/kg (Cohort A)
Cohort A: AMG 386 10mg/kg IV QW plus Sunitinib 50 mg PO QD 4 wks on/2 wks off
Drug: Sunitinib
Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of RCC and will be administered to all subjects.
Other Name: SUTENT (oral multi-kinase inhibitor)
Drug: AMG386
10 mg/kg IV QW AMG 386 will be administered until a subject develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.
Other Name: Angiogenesis inhibitor
Experimental: AMG 386 15mg/kg (Cohort B)
Cohort B: AMG 386 15mg/kg IV QW plus Sunitinib 50 mg PO QD 4 wks on/2 wks off
Drug: Sunitinib
Sunitinib will be administered 50 mg QD and is considered to be the background therapy as it is licensed for treatment of RCC and will be administered to all subjects.
Other Name: SUTENT (oral multi-kinase inhibitor)
Drug: AMG 386
15 mg/kg IV QW AMG 386 will be administered until a subject develops disease progression, clinical progression, unacceptable toxicity, withdraws consent, or death.
Other Name: Angiogenesis inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have a histologically confirmed metastatic RCC with a clear cell component
  • Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification
  • Measurable disease with at least one unidimensionally measurable lesion per RECIST guidelines with modifications
  • Adequate organ and hematological function as evidenced by laboratory studies conducted at Screening
  • ECOG of 0 or 1

Exclusion Criteria:

Disease related

  • Known history of central nervous system metastases.
  • Previous treatment (excluding surgery, prior cytokine-based immunotherapy and palliative radiotherapy) for advanced or metastatic renal cell carcinoma
  • Focal radiation therapy for palliation of pain from bony metastases within 14 days of enrollment.

Medications

  • Currently or previously treated with sunitinib or other small molecule inhibitors of VEGF
  • Currently or previously treated with agents that neutralizing VEGF
  • Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
  • Currently or previously treated with agents inhibiting the mammalian target of rapamycin (mTOR)
  • Current or within 30 days prior to enrollment treatment with immune modulators
  • Concomitant or previous use within 30 days prior to enrollment of any strong inducer of CYP3A4
  • Concomitant or previous use of amiodarone within 6 months prior to enrollment

General medical

  • Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
  • Major surgery within 28 days prior to enrollment or still recovering from prior surgery
  • Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >150 mmHg. The use of anti-hypertensive medications to control hypertension is permitted.

Other

  • Other investigational procedures are excluded
  • Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00853372

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00853372     History of Changes
Other Study ID Numbers: 20080579 
Study First Received: February 26, 2009
Last Updated: September 5, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Trebananib
Angiogenesis Inhibitors
Antineoplastic Agents
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016