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Phase 1/2 Study of PX-866 and Cetuximab

Phase 1/Phase 2
18 Years
Open (Enrolling)
Incurable Metastatic Colorectal Carcinoma, Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

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Trial Information

Phase 1/2 Study of PX-866 and Cetuximab

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

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.

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Diana Hausman, MD

Investigator Role:

Study Director

Investigator Affiliation:

Oncothyreon Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

January 2014

Related Keywords:

  • Incurable Metastatic Colorectal Carcinoma
  • Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
  • CRC
  • PX-866
  • Cetuximab
  • Colon
  • Head and Neck
  • Colorectal cancer
  • Squamous cell carcinoma
  • PI-3K
  • PI3 kinase
  • PI3K
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Colorectal Neoplasms
  • Head and Neck Neoplasms



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