Phase 1 and 2 Study of PX-866 and Cetuximab

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Oncothyreon Inc.
ClinicalTrials.gov Identifier:
NCT01252628
First received: December 1, 2010
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

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).


Condition Intervention Phase
Incurable Metastatic Colorectal Carcinoma
Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Drug: PX-866 and cetuximab
Drug: Cetuximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/2 Study of PX-866 and Cetuximab

Resource links provided by NLM:


Further study details as provided by Oncothyreon Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 178
Study Start Date: December 2010
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab and PX-866 (SCCHN)
Phase 2 (Squamous Cell Carcinoma of the Head and Neck)
Drug: PX-866 and cetuximab
PX-866 administered at the MTD/RD in combination with cetuximab in patients administered weekly on a 21 day cycle.
Other Name: Erbitux
Active Comparator: Cetuximab (SCCHN)
Phase 2 (Squamous Cell Carcinoma of the Head and Neck)
Drug: Cetuximab
Cetuximab administered weekly on a 21 day cycle, as standard of care in patients.
Other Name: Erbitux
Experimental: Cetuximab and PX-866 (CRC)
Phase 2 (Colorectal Carcinoma)
Drug: PX-866 and cetuximab
PX-866 administered at the MTD/RD in combination with cetuximab in patients administered weekly on a 21 day cycle.
Other Name: Erbitux
Active Comparator: Cetuximab (CRC)
Phase 2 (Colorectal Carcinoma)
Drug: Cetuximab
Cetuximab administered weekly on a 21 day cycle in patients, as standard of care.
Other Name: Erbitux

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01252628

  Show 40 Study Locations
Sponsors and Collaborators
Oncothyreon Inc.
Investigators
Study Director: Diana Hausman, MD Oncothyreon Inc.
  More Information

No publications provided

Responsible Party: Oncothyreon Inc.
ClinicalTrials.gov Identifier: NCT01252628     History of Changes
Other Study ID Numbers: PX-866-003
Study First Received: December 1, 2010
Last Updated: May 10, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Oncothyreon Inc.:
CRC
SCCHN
PX-866
Cetuximab
ERBITUX
Colon
Head and Neck
Colorectal cancer
Squamous cell carcinoma
PI-3K
PI3 kinase
PI3K

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Colorectal Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 14, 2014