Cabozantinib and Panitumumab to Treat KRAS Wild-Type Metastatic Colorectal Cancer

NCT02008383 | Completed Phase 1 DMC

• 1 other identifier: Pro00049983
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

There will be three parts to this phase I study: 1) the Combination Dose Finding cohort; 2) the Combination Expansion cohort; and 3) the Monotherapy MET Amplified cohort. In the Combination Dose Finding cohort and the Combination Expansion cohort, we will combine cabozantinib and panitumumab in patients with KRAS wild-type metastatic colorectal cancer (CRC). In the Monotherapy MET Amplified cohort, we will screen at least 50 patients for MET gene amplification ("MET amplification"). Patients with MET amplification will receive cabozantinib only (monotherapy). The primary objective of this open-label phase Ib trial are:

1. 1.To determine the maximum tolerated dose and the recommended phase II dose for the combination of cabozantinib and panitumumab in patients with KRAS wild-type metastatic colorectal cancer and
2. 2.To identify the objective response rate (ORR) of cabozantinib monotherapy in patients with prospectively identified MET amplified metastatic colorectal cancer.
3. 3.To describe the non-dose limiting toxicities of cabozantinib and panitumumab.
4. 4.To describe the clinical activity (ORR, PFS, OS) of cabozantinib and panitumumab.
5. 5.To describe the safety and tolerability of cabozantinib monotherapy in patients with MET amplified colorectal cancer.
6. 6.To describe the clinical activity (PFS, OS) of cabozantinib monotherapy in patients with MET amplified colorectal cancer.

Conditions

Colorectal Cancer

Keywords

Colorectal cancer; Panitumumab; Cabozantinib

Outcome Measures

Primary Outcomes (2)

• Recommended phase II dose (RPTD) for the combination of cabozantinib and panitumumab

  RPTD for the study will be determined at the completion of Phase I dose escalation cohort; estimated as 1 year

• Objective response rate (ORR) of cabozantinib monotherapy in patients with prospectively identified MET amplified metastatic colorectal cancer

  Approximately every 8 weeks and/or restaging

Secondary Outcomes (7)

• Non-dose limiting toxicities of cabozantinib and panitumumab.

  Continuous, every 4 weeks minimum until end of study estimated at 4 years

• Response rate of cabozantinib and panitumumab

  approximately every 8 weeks and/or restaging

• Progression free survival associated with the cabozantinib and panitumumab regimen

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

• Overall survival associated with the cabozantinib and panitumumab regimen

  From date of randomization until the date of death from any cause assessed up to 60 months

• Progression free survival associated with cabozantinib monotherapy in patients with MET amplified colorectal cancer

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Study Arms (2)

Cabozantinib and Panitumumab

EXPERIMENTAL

60 mg Cabozantinib PO daily and 6 mg/kg Panitumumab IV every 2 weeks.

Biological: Panitumumab; Drug: Cabozantinib

Cabozantinib

EXPERIMENTAL

60 mg Cabozantinib PO daily.

Drug: Cabozantinib

Interventions

Panitumumab BIOLOGICAL

The FDA approved dose for panitumumab is 6mg/kg IV, every two weeks. This is the dose and schedule that will be used in this study.

Also known as: Vectibix

Cabozantinib and Panitumumab

Cabozantinib DRUG

There will be three parts to this phase I study: 1) the Combination Dose Finding cohort; 2) the Combination Expansion cohort; and 3) the Monotherapy MET Amplified cohort. Cabozantinib will start at a dose of 60 mg daily with reductions to 40 and 20 mg daily possible in the dose finding cohort. The combination expansion cohort dose will determined by the dose finding cohort. The Monotherapy MET Amplified cohort will recieve 60 mg Cabozantinib daily.

Also known as: Cometriq

Cabozantinib; Cabozantinib and Panitumumab

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed and radiographically measurable KRAS wild-type adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable. Subjects must have been treated with a fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan and bevacizumab or have contraindication to such treatment.
• Prior treatment with anti-EGFR therapy (either panitumumab or cetuximab).
• At least one site of disease that is measurable by RECIST (version 1.1) criteria that has not been previously irradiated; if the patient has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy greater than 3 months.
• Capable of understanding and complying with the protocol requirements and has signed the informed consent document.
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,000/μl without colony stimulating factor support
• Platelets ≥ 75,000/μl
• Hemoglobin ≥ 8 g/dL
• AST/ALT ≤ 3 X upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
• Serum albumin ≥ 2.5 g/dL

You may not qualify if:

• Presence of or known history of brain/ CNS tumor or metastases.
• KRAS exon 2 (codons 12 or 13) mutation detected in tumor tissue specimen.
• Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study, including impaired heart function or clinically significant heart disease.
• Concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). Low dose aspirin (≤ 81 mg/day), low-dose warfarin (≤ 1 mg/day), and prophylactic LMWH are permitted.
• Previously experienced any of the following:
• clinically significant gastrointestinal bleeding within the last 6 months
• hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within the last 3 months
• any other signs indicative of pulmonary hemorrhage within the last 3 months
• Radiographic evidence of cavitating pulmonary lesion(s).
• Tumor in contact with, invading or encasing any major blood vessels.
• Evidence of endotracheal or endobronchial tumor.
• Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• i. Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
• ii. Any history of congenital long QT syndrome

Sponsors & Collaborators

• John Strickler, M.D.: lead
• Exelixis: collaborator

Study Sites (1)

Duke Cancer Center, Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• Strickler JH, Rushing CN, Uronis HE, Morse MA, Niedzwiecki D, Blobe GC, Moyer AN, Bolch E, Webb R, Haley S, Hatch AJ, Altomare IP, Sherrill GB, Chang DZ, Wells JL, Hsu SD, Jia J, Zafar SY, Nixon AB, Hurwitz HI. Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer. Oncologist. 2021 Jun;26(6):465-e917. doi: 10.1002/onco.13678. Epub 2021 Feb 9.

  PMID: 33469991 RESULT

• Jia J, Howard L, Liu Y, Starr MD, Brady JC, Niedzwiecki D, Strickler JH, Nixon AB. Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers. Cancer Chemother Pharmacol. 2022 Mar;89(3):413-422. doi: 10.1007/s00280-022-04404-8. Epub 2022 Feb 16.

  PMID: 35171350 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Panitumumab; cabozantinib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal 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

Study Officials

• John Strickler, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 3, 2013
• First Posted: December 11, 2013
• Study Start: January 1, 2014
• Primary Completion: May 10, 2018
• Study Completion: August 29, 2018
• Last Updated: February 12, 2021

Record last verified: 2021-02

Locations

US (1)