Phase 1 and 2 Study of PX-866 and Cetuximab

NCT01252628 | Completed Phase 1 DMC

• 1 other identifier: PX-866-003
• Study Type: interventional
• Target: 178
• Locations: 2 countries
• Sites: 40

Brief Summary

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).

Conditions

Incurable Metastatic Colorectal Carcinoma; Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Keywords

CRC; SCCHN; PX-866; Cetuximab; ERBITUX; Colon; Head and Neck; Colorectal cancer; Squamous cell carcinoma; PI-3K; PI3 kinase; PI3K

Outcome Measures

Primary Outcomes (1)

• 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.

  21 days

Study Arms (4)

PX-866 (SCCHN)

EXPERIMENTAL

Phase 2 (Squamous Cell Carcinoma of the Head and Neck)

Drug: PX-866 (SCCHN); Drug: Cetuximab (SCCHN)

Cetuximab (SCCHN)

ACTIVE COMPARATOR

Phase 2 (Squamous Cell Carcinoma of the Head and Neck)

Drug: Cetuximab (SCCHN)

PX-866 (CRC)

EXPERIMENTAL

Phase 2 (Colorectal Carcinoma)

Drug: PX-866 (CRC); Drug: Cetuximab (CRC)

Cetuximab (CRC)

ACTIVE COMPARATOR

Phase 2 (Colorectal Carcinoma)

Drug: Cetuximab (CRC)

Interventions

PX-866 (SCCHN) DRUG

PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.

PX-866 (SCCHN)

Cetuximab (SCCHN) DRUG

Cetuximab administered weekly on a 21 day cycle, as standard of care in patients.

Also known as: Erbitux

Cetuximab (SCCHN); PX-866 (SCCHN)

PX-866 (CRC) DRUG

PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.

PX-866 (CRC)

Cetuximab (CRC) DRUG

Cetuximab administered weekly on a 21 day cycle in patients, as standard of care.

Also known as: Erbitux

Cetuximab (CRC); PX-866 (CRC)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Cascadian Therapeutics Inc.: lead

Study Sites (40)

Birmingham Hematology and Oncology Assocs.

Birmingham, Alabama, 35223, United States

Location

University of Alabama Birmingham

Birmingham, Alabama, 35249, United States

Location

Southwest Cancer Care

Escondido, California, 92025, United States

Location

Monterey Bay Oncology

Monterey, California, 93940, United States

Location

Ventura County Hematology Oncology Specialists

Oxnard, California, 93030, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Eastern Colorado Health Care System - (Denver VA)

Denver, Colorado, 80220, United States

Location

George Washington University - Medical Faculty Associates

Washington D.C., District of Columbia, 20037, United States

Location

Integrated Community Oncology Network

Jacksonville, Florida, 32256, United States

Location

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Pasco Pinellas Cancer Center

New Port Richey, Florida, 34652, United States

Location

Peachtree Hematology-Oncology Consultants

Atlanta, Georgia, 30318, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Saint Louis Cancer Care LLP

Bridgeton, Missouri, 63044, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Northwest Cancer Specialists, P.C.

Tualatin, Oregon, 97062, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

Mary Crowley Cancer Center

Dallas, Texas, 75230, United States

Location

Texas Oncology - Baylor Charles A. Sammons

Dallas, Texas, 75246, United States

Location

Texas Oncology - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - Seton Williamson

Round Rock, Texas, 78665, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Virginia Oncology Associates

Newport News, Virginia, 23606, United States

Location

Oncology and Hematology Associates of Southwest Virginia

Roanoke, Virginia, 24014, United States

Location

Columbia Basin Hematology and Oncology

Kennewick, Washington, 99336, United States

Location

Medical Oncology Associates

Spokane, Washington, 99208, United States

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Northeast Cancer Centre of Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Thunder Bay Regional Health Sciences Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Hôpital Charles-LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Cité de la Santé de Laval

Laval, Quebec, H7M 3L9, Canada

Location

Maisonneuve-Rosemont Hospital Research Centre

Montreal, Quebec, H1T 2M4, Canada

Location

MeSH Terms

Conditions

Recurrence; Colorectal Neoplasms; Carcinoma, Squamous Cell; Hereditary Sensory and Autonomic Neuropathies

Interventions

PX-866; Cetuximab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

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

Study Officials

• Diana Hausman, MD

  Cascadian Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 3, 2010
• Study Start: December 1, 2010
• Primary Completion: November 1, 2013
• Study Completion: January 1, 2014
• Last Updated: May 16, 2018

Record last verified: 2015-06

Locations

US (31); CA (9)