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

NantBioscience

Status and phase: Completed; Phase 2; Phase 1

Conditions: Metastatic Colorectal Cancer; Gastrointestinal Cancer; Colon Cancer; Rectal Cancer; Colorectal Cancer

Treatments: Drug: Placebo; Drug: Rilotumumab; Drug: Panitumumab; Drug: Ganitumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00788957

20060447

Details and patient eligibility

About

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.

Full 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.

Enrollment: 177 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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177 participants in 6 patient groups

Part 1: Panitumumab + Rilotumumab

Experimental group

Description:

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.

Treatment:

Drug: Panitumumab

Drug: Rilotumumab

Part 2: Panitumumab Alone

Active Comparator group

Description:

Participants received panitumumab 6 mg/kg and placebo by intravenous infusion once every 2 weeks until progressive disease, intolerability, withdrawal, death or sponsor decision.

Treatment:

Drug: Panitumumab

Part 2: Panitumumab + Rilotumumab

Experimental group

Description:

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.

Treatment:

Drug: Panitumumab

Drug: Rilotumumab

Drug: Placebo

Part 2: Panitumumab + Ganitumab

Experimental group

Description:

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.

Treatment:

Drug: Ganitumab

Drug: Panitumumab

Drug: Placebo

Part 3: Rilotumumab

Experimental group

Description:

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.

Treatment:

Drug: Rilotumumab

Drug: Placebo

Part 3: Ganitumab

Experimental group

Description:

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.

Treatment:

Drug: Ganitumab

Drug: Placebo