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

NCT00788957 | Completed Phase 1 Results

• 1 other identifier: 20060447
• Study Type: interventional
• Target: 177
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (2)

• Part 1: Number of Participants With Dose-limiting Toxicities (DLT)

  A DLT is defined as any grade 3 or 4 rilotumumab-related or combination (panitumumab and rilotumumab)-related adverse event or laboratory abnormality that is deemed clinically significant by the investigator

  7 weeks

• Part 2: Percentage of Participants With an Objective Response

  An objective response is defined as a confirmed complete (CR) or partial response (PR) no less than 4 weeks after the criteria for response are first met, determined by the investigator considering the radiologic response of all existing target and non-target lesions, evidence of new lesions, and cytology evaluation (as appropriate) according to the Modified-Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 criteria: CR: Disappearance of all target and non-target and no new lesions. PR: At least a 30% decrease in the size of target lesions with no increase in non-target lesions, or, the disappearance of all target lesions and persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease. Participants without a post-baseline assessment were considered non-responders. Tumor assessments up to the initiation of another anti-tumor therapy including the Part 3 treatment, if applicable, were used.

  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 (19)

• Duration of Response - Part 2

  From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.

• Time to Response - Part 2

  From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.

• Disease Control Rate - Part 2

  From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.

• Progression-free Survival (PFS) - Part 2

  From the date of first dose until the data cut-off date of 23 July 2010. Median follow-up time was 30 weeks.

• On-treatment Progression-free Survival (PFS) - Part 2

  From the date of first dose until the data cut-off date of 23 July 2010. Up to 56 weeks.

Study Arms (6)

Part 1: Panitumumab + Rilotumumab

EXPERIMENTAL

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; Drug: Rilotumumab

Part 2: Panitumumab Alone

ACTIVE COMPARATOR

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

Part 2: Panitumumab + Rilotumumab

EXPERIMENTAL

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; Drug: Rilotumumab; Drug: Placebo

Part 2: Panitumumab + Ganitumab

EXPERIMENTAL

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; Drug: Ganitumab; Drug: Placebo

Part 3: Rilotumumab

EXPERIMENTAL

Participants randomized to Panitumumab Alone in Part 2 who had disease progression (radiographic or clinical) or intolerability were re-randomized in Part 3 to receive rilotumumab 10 mg/kg every 2 weeks until disease progression, intolerability, withdrawal, death, or sponsor decision.

Drug: Rilotumumab; Drug: Placebo

Part 3: Ganitumab

EXPERIMENTAL

Participants randomized to Panitumumab Alone in Part 2 who had disease progression (radiographic or clinical) or intolerability were re-randomized in Part 3 to receive ganitumab 12 mg/kg every 2 weeks until disease progression, intolerability, withdrawal, death, or sponsor decision.

Drug: Ganitumab; Drug: Placebo

Interventions

Panitumumab DRUG

Panitumumab for intravenous infusion

Also known as: Vectibix®

Part 1: Panitumumab + Rilotumumab; Part 2: Panitumumab + Ganitumab; Part 2: Panitumumab + Rilotumumab; Part 2: Panitumumab Alone

Ganitumab DRUG

Ganitumab for intravenous infusion

Also known as: AMG 479

Part 2: Panitumumab + Ganitumab; Part 3: Ganitumab

Rilotumumab DRUG

Rilotumumab for intravenous infusion

Also known as: AMG 102

Part 1: Panitumumab + Rilotumumab; Part 2: Panitumumab + Rilotumumab; Part 3: Rilotumumab

Placebo DRUG

Placebo intravenous infusion

Part 2: Panitumumab + Ganitumab; Part 2: Panitumumab + Rilotumumab; Part 3: Ganitumab; Part 3: Rilotumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NantBioScience, Inc.: lead

Related Publications (2)

• 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.

  PMID: 24919569 BACKGROUND

• 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.

  PMID: 26049686 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colonic Neoplasms; Colorectal Neoplasms; Gastrointestinal Neoplasms; Rectal Neoplasms

Interventions

Panitumumab; ganitumab; rilotumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Part 3 of the study did not reach the accrual goal. Only 24 out of the 42 planned subjects received treatment in Part 3 of the study.

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@Immunitybio.com

855-797-9277

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2008
• First Posted: November 11, 2008
• Study Start: October 27, 2008
• Primary Completion: July 23, 2010
• Study Completion: July 23, 2010
• Last Updated: August 7, 2024
• Results First Posted: July 20, 2015

Record last verified: 2024-07