Phase 1 and 2 Study of PX-866 and Cetuximab

May 14, 2018 updated by: Cascadian Therapeutics Inc.

Phase 1/2 Study of PX-866 and Cetuximab

The purpose of this Phase 1/2 open-label study is to determine the safety and efficacy of a cetuximab and PX-866 combination treatment. In the Phase 1 part of the study, the dose of PX-866 to be given in combination with cetuximab will be determined in patients with incurable metastatic CRC or incurable progressive, recurrent or metastatic SCCHN. The Phase 2 part of the study is a randomized evaluation of the antitumor activity and safety of PX-866 in combination with cetuximab versus cetuximab alone in patients with either incurable metastatic CRC who have a history of progression or recurrence following prior irinotecan and oxaliplatin containing regimens or are intolerant of irinotecan (Group 1) or incurable progressive, recurrent or metastatic SCCHN (Group 2).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Phase 1 will determine the maximally tolerated or recommended dose of PX-866 to be given orally on Days 1-21 in combination with cetuximab 250 mg/m2 administered IV weekly on Days 1, 8, and 15 of a 21-day cycle. All patients will receive an initial loading dose of 400 mg/m2 cetuximab rather than 250 mg/m2 on Cycle 1 Day 1. Patients may receive premedication with an H1 antagonist per the cetuximab package insert. Up to 3 dose levels of PX-866 will be evaluated to determine the MTD/RD in cohorts of up to 6 patients using a standard 3+3 dose-escalation design. At least 6 patients will be treated at the MTD/RD. All patients in Phase 1 will be required to undergo PK assessments during Cycle 1 Week 3 to measure cetuximab levels. Exploratory PD assessments will include evaluation of changes in levels of fasting C-peptide as well as changes in EGFR and PI-3K signaling pathways in peripheral blood mononuclear cells (PBMC) and platelets. Additional optional evaluations will include changes in EGFR and PI-3K signaling in paired tumor biopsies provided before and after one cycle of treatment. All patients will be asked, but not required, to provide an archived tumor biopsy sample for evaluation for potential biomarkers of response to PX-866 and cetuximab.

Phase 2 is an open-label, randomized evaluation of the antitumor activity and safety of PX-866 administered orally or via PEG tube (if applicable) at the MTD/RD in combination with cetuximab, versus cetuximab alone in cetuximab-naïve patients with incurable metastatic CRC who have a history of progression or recurrence following prior irinotecan and oxaliplatin containing regimens or are intolerant of irinotecan (Group 1) or patients with incurable progressive, recurrent or metastatic SCCHN (Group 2). Seventy two evaluable patients (36 patients per arm) will be evaluated per indication. Patients will be randomized 1:1 to receive PX-866 + cetuximab or cetuximab alone.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency - Vancouver Centre
    • Ontario
      • Barrie, Ontario, Canada, L4M 6M2
        • Royal Victoria Regional Health Centre
      • London, Ontario, Canada, N6A 4L6
        • London Regional Cancer Program
      • Sudbury, Ontario, Canada, P3E 5J1
        • Northeast Cancer Centre of Health Sciences North
      • Thunder Bay, Ontario, Canada, P7B 6V4
        • Thunder Bay Regional Health Sciences Centre
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • Hôpital Charles-LeMoyne
      • Laval, Quebec, Canada, H7M 3L9
        • Cité de la santé de Laval
      • Montreal, Quebec, Canada, H1T 2M4
        • Maisonneuve-Rosemont Hospital Research Centre
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • University of Alabama Birmingham
      • Birmingham, Alabama, United States, 35223
        • Birmingham Hematology and Oncology Assocs.
    • California
      • Escondido, California, United States, 92025
        • Southwest Cancer Care
      • Monterey, California, United States, 93940
        • Monterey Bay Oncology
      • Oxnard, California, United States, 93030
        • Ventura County Hematology Oncology Specialists
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, United States, 80220
        • Eastern Colorado Health Care System - (Denver VA)
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • George Washington University - Medical Faculty Associates
    • Florida
      • Jacksonville, Florida, United States, 32256
        • Integrated Community Oncology Network
      • Miami, Florida, United States, 33176
        • Advanced Medical Specialties
      • New Port Richey, Florida, United States, 34652
        • Pasco Pinellas Cancer Center
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Peachtree Hematology-Oncology Consultants
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Center for Cancer and Blood Disorders
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Missouri
      • Bridgeton, Missouri, United States, 63044
        • Saint Louis Cancer Care LLP
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • Oregon
      • Tualatin, Oregon, United States, 97062
        • Northwest Cancer Specialists, P.C.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • MUSC Hollings Cancer Center
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology - Baylor Charles A. Sammons
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Center
      • Fort Worth, Texas, United States, 76104
        • Texas Oncology - Fort Worth
      • Round Rock, Texas, United States, 78665
        • Texas Oncology - Seton Williamson
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC
      • Newport News, Virginia, United States, 23606
        • Virginia Oncology Associates
      • Newport News, Virginia, United States, 23601
        • Peninsula Cancer Institute
      • Roanoke, Virginia, United States, 24014
        • Oncology and Hematology Associates of Southwest Virginia
    • Washington
      • Kennewick, Washington, United States, 99336
        • Columbia Basin Hematology and Oncology
      • Spokane, Washington, United States, 99208
        • Medical Oncology Associates

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • At least 18 years at time of consent
  • Use of a medically accepted form of contraception from the time of consent to completion of all follow-up study visits
  • If female of child-bearing potential, negative pregnancy test
  • Signed an informed consent
  • Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST)
  • Documentation available for last prior systemic treatment including dates of treatment, best response to treatment, duration of best response, and reason for discontinuation of treatment
  • Eastern Cooperative Oncology Group (ECOG) 0 or 1
  • Group 1: Patients with incurable metastatic CRC with a history of progression or recurrence following prior irinotecan and oxaliplatin containing regimens. Patients who have a history of intolerance of irinotecan based therapy or ineligibility to receive irinotecan are also eligible as long as they have received a prior oxaliplatin containing regimen.
  • Group 2: Patients with incurable SCCHN with a history of progression or recurrence following at least one prior platinum based chemotherapy or chemotherapy/radiation containing regimen. Patients who have a history of intolerance of platinum based therapy or history of ineligibility to receive a platinum based regimen are also eligible. SCCHN patients who received cetuximab as a radiosensitizer for locally advanced disease and completed treatment at least 6 months prior to start of study drug treatment are eligible
  • In the opinion of the clinical investigator, life expectancy of greater than 3 months
  • Adequate hematologic function
  • Adequate hepatic function
  • Creatinine level ≤1.5 x ULN
  • Serum magnesium ≥ LLN.

Exclusion Criteria:

  • Has medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures
  • Is breastfeeding
  • Treatment with any systemic chemotherapy, epidermal growth factor receptor (EGFR) inhibitor, radiation or experimental agent within 4 weeks of study drug dosing
  • Received prior cetuximab, except as defined in inclusion criteria
  • Previous treatment with a phosphatidylinositol 3-kinase (PI-3K) inhibitor
  • Known human immunodeficiency virus (HIV)
  • Poorly controlled diabetes mellitus (IFCC-HbA1C ≥ 53 mmol/mol or DCCT -HbA1C ≥ 7%)
  • Kras mutation in codon 12 or 13 (CRC patients only)
  • Known or suspected clinically active brain metastases. Previously treated and stable brain metastases are allowable. Stable brain metastases are defined as no change on CT scan or MRI for minimum of two months AND no change in steroid dose for a minimum of four weeks, unless change due to intercurrent infection or other acute event)
  • Any other significant medical or psychiatric condition that in the opinion of the investigator renders the patient inadequate for participation
  • History of severe hypersensitivity to cetuximab

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PX-866 (SCCHN)
Phase 2 (Squamous Cell Carcinoma of the Head and Neck)
Drug: PX-866 (SCCHN)
PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.
Drug: Cetuximab (SCCHN)
Cetuximab administered weekly on a 21 day cycle, as standard of care in patients.
Other Names:
  • Erbitux
Active Comparator: Cetuximab (SCCHN)
Phase 2 (Squamous Cell Carcinoma of the Head and Neck)
Drug: Cetuximab (SCCHN)
Cetuximab administered weekly on a 21 day cycle, as standard of care in patients.
Other Names:
  • Erbitux
Experimental: PX-866 (CRC)
Phase 2 (Colorectal Carcinoma)
Drug: PX-866 (CRC)
PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.
Drug: Cetuximab (CRC)
Cetuximab administered weekly on a 21 day cycle in patients, as standard of care.
Other Names:
  • Erbitux
Active Comparator: Cetuximab (CRC)
Phase 2 (Colorectal Carcinoma)
Drug: Cetuximab (CRC)
Cetuximab administered weekly on a 21 day cycle in patients, as standard of care.
Other Names:
  • Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The evaluation of antitumor effects of PX-866 in combination with cetuximab versus cetuximab in patients with incurable metastatic colorectal cancer and/or patients with incurable progressive, recurrent or metastatic SCC of the head and neck.
Time Frame: 21 days
21 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cascadian Therapeutics Inc.

Investigators

  • Study Director: Diana Hausman, MD, Cascadian Therapeutics Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

January 1, 2014

Study Registration Dates

First Submitted

December 1, 2010

First Submitted That Met QC Criteria

December 1, 2010

First Posted (Estimate)

December 3, 2010

Study Record Updates

Last Update Posted (Actual)

May 16, 2018

Last Update Submitted That Met QC Criteria

May 14, 2018

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PX-866-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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