Panitumumab Combination Study With Rilotumumab or Ganitumab in Wild-type Kirsten Rat Sarcoma Virus Oncogene Homolog (KRAS) Metastatic Colorectal Cancer (mCRC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00788957
First received: October 23, 2008
Last updated: January 22, 2015
Last verified: November 2014
  Purpose

This study is a global, multicenter, open-label phase 1b and randomized, double-blinded, 2 part, phase 2 study designed to evaluate the safety and efficacy of rilotumumab or ganitumab in combination with panitumumab versus panitumumab alone in patients with metastatic colorectal cancer whose tumors are wild-type KRAS status.


Condition Intervention Phase
Colon Cancer
Colorectal Cancer
Gastrointestinal Cancer
Metastatic Colorectal Cancer
Rectal Cancer
Drug: Panitumumab
Drug: Ganitumab
Drug: Rilotumumab
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Phase 1b/2 Trial of AMG 102 or AMG 479 in Combination With Panitumumab Versus Panitumumab Alone in Subject With Wild-Type KRAS Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Phase 1: subject incidence of selected adverse events and laboratory abnormalities [ Time Frame: Phase 1: after ~6 subjects enrolled + 1-2 months after the 6th subject is enrolled ] [ Designated as safety issue: Yes ]
  • Phase 2: incidence of objective response [ Time Frame: Phase 2: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]
  • Time to response [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]
  • Disease control [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]
  • Incidence of adverse events and clinical laboratory abnormalities [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: Yes ]
  • Incidence of antibody formation to panitumumab, AMG 102, and AMG 479 [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: Yes ]
  • Cmin, Cmax, and AUC for panitumumab and AMG 102 [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]
  • Cmin and Cmax for panitumumab, AMG 102, and AMG 479 [ Time Frame: after ~126 subjects randomized + ~26 months after the 126th subject is randomized ] [ Designated as safety issue: No ]

Enrollment: 153
Study Start Date: October 2008
Study Completion Date: October 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
Drug: Panitumumab
Panitumumab for intravenous infusion
Other Name: Vectibix®
Drug: Rilotumumab
Rilotumumab for intravenous infusion
Other Name: AMG 102
Active Comparator: Part 2: Panitumumab Alone
Participants received panitumumab 6 mg/kg and placebo by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
Drug: Panitumumab
Panitumumab for intravenous infusion
Other Name: Vectibix®
Drug: Placebo
Placebo intravenous infusion
Experimental: Part 2: Panitumumab + Rilotumumab
Participants received panitumumab 6 mg/kg and rilotumumab 10 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
Drug: Panitumumab
Panitumumab for intravenous infusion
Other Name: Vectibix®
Drug: Rilotumumab
Rilotumumab for intravenous infusion
Other Name: AMG 102
Experimental: Part 2: Panitumumab + Ganitumab
Participants received panitumumab 6 mg/kg and ganitumab 12 mg/kg by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.
Drug: Panitumumab
Panitumumab for intravenous infusion
Other Name: Vectibix®
Drug: Ganitumab
Ganitumab for intravenous infusion
Other Name: AMG 479

Detailed Description:

This study consisted of 3 parts:

Part 1: determination of the tolerable dose of rilotumumab in combination with panitumumab to be administered in Part 2.

Part 2: Comparison of the safety and efficacy of rilotumumab or ganitumab in combination with panitumumab versus that of panitumumab alone. In Part 2, participants were randomized 1:1:1 into 3 cohorts: 6 mg/kg panitumumab plus 10 mg/kg rilotumumab, 6 mg/kg panitumumab plus 12 mg/kg ganitumab, or 6 mg/kg panitumumab and placebo (panitumumab alone cohort). Panitumumab was administered open-label, and rilotumumab and ganitumab were double-blinded.

Part 3: Exploratory evaluation of the safety and efficacy of the rilotumumab and ganitumab monotherapy following treatment with panitumumab in Part 2. In Part 3, eligible participants who terminated panitumumab treatment in the Panitumumab Alone arm of Part 2 due to disease progression or intolerability could be randomized 1:1 into 2 double-blind cohorts: 10 mg/kg rilotumumab or 12 mg/kg ganitumab.

Participants who permanently discontinued all the investigational products completed a safety follow-up visit 30 days and a follow-up visit 60 days after the last dose of investigational product. Participants were followed for radiographic disease progression and survival every 3 months after the 30-day safety follow-up visit for up to 2 years after the last participant was enrolled in Part 2.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • metastatic adenocarcinoma of the colon or rectum
  • wild-type KRAS tumor status
  • radiographic evidence of disease progression during or following treatment with irinotecan and/or oxaliplatin containing chemotherapy for mCRC
  • measurable disease >/= 20 mm per Response Evaluation Criteria In Solid Tumors (RECIST)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • adequate laboratory values

Exclusion Criteria:

  • history of central nervous system (CNS) metastases
  • history of another primary cancer, unless:
  • curatively resected non-melanomatous skin cancer
  • curatively treated cervical carcinoma in situ
  • other primary solid tumor treated with curative intent and no known active disease present for >/= 5 years
  • prior treatment with an anti-epithelial growth factor receptor (EGFR), hepatocyte growth factor receptor (HGFR, c-MET), and/or insulin-like growth factor receptor (IGFR) inhibitor
  • prior treatment with AMG 102 or AMG 479
  • prior treatment with chemotherapy or radiotherapy </= 21 days
  • prior treatment with targeted therapy </= 30 days
  • known allergy or hypersensitivity to panitumumab, AMG 102, or AMG 479
  • history of interstitial lung disease
  • clinically significant cardiovascular disease </= 1 year
  • active inflammatory bowel disease
  • known human immunodeficiency virus (HIV), hepatitis C, or hepatitis B infection
  • any co-morbid disease or condition that could increase the risk of toxicity
  • serious or non-healing wound </= 35 days
  • any uncontrolled concurrent illness or history of any medical condition that could interfere with the interpretation of the study results
  • major surgical procedure </= 35 days or minor surgical procedure </= 14 days
  • other investigational procedures or drugs </= 30 days
  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: NCT00788957

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

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00788957     History of Changes
Other Study ID Numbers: 20060447
Study First Received: October 23, 2008
Last Updated: January 22, 2015
Health Authority: Canada: Health Canada
European Union: European Medicines Agency
United States: Food and Drug Administration
United States: Quorom Institutional Review Board
United States: Western Institutional Review Board

Keywords provided by Amgen:
AMG 479
panitumumab
vectibix
AMG 102
colon cancer
rectal cancer
colorectal cancer
metastatic colorectal cancer
EGFR inhibitor
IGF inhibitor
c-MET inhibitor

Additional relevant MeSH terms:
Colorectal Neoplasms
Gastrointestinal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 30, 2015