Clinical trial NCT00788957: Panitumumab Combination Study With Rilotumumab or Ganitumab in Wild-type Kirsten Rat Sarcoma Virus Oncogene Homolog (KRAS) Metastatic Colorectal Cancer (mCRC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colon Cancer
Colorectal Cancer
Gastrointestinal Cancer
Metastatic Colorectal Cancer
Rectal Cancer
Keywords: panitumumab
vectibix
AMG 102
AMG 479
colon cancer
rectal cancer
colorectal cancer
metastatic colorectal cancer
EGFR inhibitor
IGF inhibitor
c-MET inhibitor
Lead sponsor: NantBioScience, Inc.
Sponsor class: INDUSTRY
First posted: 2008-11-11
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Part 1: Number of Participants With Dose-limiting Toxicities (DLT)
timeFrame: 7 weeks
measure: Part 2: Percentage of Participants With an Objective Response
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
Secondary outcomes:
measure: Duration of Response - Part 2
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
measure: Time to Response - Part 2
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
measure: Disease Control Rate - Part 2
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
measure: Progression-free Survival (PFS) - Part 2
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
measure: On-treatment Progression-free Survival (PFS) - Part 2
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Up to 56 weeks.
measure: Overall Survival - Part 2
timeFrame: From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.
measure: Cmin, Cmax of Panitumumab
timeFrame: 14 days
measure: Cmin, Cmax, for Rilotumumab
timeFrame: 14 days
measure: Cmin for Panitumumab - Part 2
timeFrame: Up to 23 weeks
measure: Cmax for Panitumumab - Part 2
timeFrame: Up to 23 weeks
measure: Cmin for Rilotumumab - Part 2
timeFrame: Up to 23 weeks
measure: Cmax for Rilotumumab - Part 2
timeFrame: Up to 23 weeks
measure: Cmin for Ganitumab - Part 2
timeFrame: Up to 23 weeks
measure: Cmax for Ganitumab - Part 2
timeFrame: Up to 23 weeks
measure: Total Anti-Panitumumab Antibody Incidence - Part 2
timeFrame: First dose of any study drug and before 120 days of last dose of study drugs; up to 1 year, eight months
measure: Total Anti-AMG 102 Antibody Incidence - Part 2
timeFrame: First dose of any study drug and before 120 days of last dose of study drugs, up to 1 year, eight months.
measure: Total Anti-AMG 479 Antibody Incidence - Part 2
timeFrame: First dose of any study drug and before 120 days of last dose of study drugs, up to 1 year, eight months.
measure: AUC for Rilotumumab
timeFrame: 14 Days
measure: AUC for Panitumumab
timeFrame: 14 Days
Other outcomes:
Locations:
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Van Cutsem E, Eng C, Nowara E, Swieboda-Sadlej A, Tebbutt NC, Mitchell E, Davidenko I, Stephenson J, Elez E, Prenen H, Deng H, Tang R, McCaffery I, Oliner KS, Chen L, Gansert J, Loh E, Smethurst D, Tabernero J. Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer. Clin Cancer Res. 2014 Aug 15;20(16):4240-50. doi: 10.1158/1078-0432.CCR-13-2752. Epub 2014 Jun 11.
citation: Peeters M, Kafatos G, Taylor A, Gastanaga VM, Oliner KS, Hechmati G, Terwey JH, van Krieken JH. Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials. Eur J Cancer. 2015 Sep;51(13):1704-13. doi: 10.1016/j.ejca.2015.05.017. Epub 2015 Jun 3.