Phase 1 and 2 Study of PX-866 and Cetuximab



Status:Completed
Conditions:Colorectal Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:5/18/2018
Start Date:December 2010
End Date:January 2014

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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).

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.

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
We found this trial at
32
sites
8503 Arlington Blvd., Ste. 400
Fairfax, Virginia 22031
(703) 280-5390
Virginia Cancer Specialists, PC Now the world's most advanced cancer treatment capabilities can be found...
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1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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800 Washington St
Boston, Massachusetts 02111
(617) 636-5000
Tufts Medical Center Tufts Medical Center is an internationally-respected academic medical center – a teaching...
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Boston, MA
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8940 N Kendall Dr # 300E
Miami, Florida 33176
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5347 Main St # 203
New Port Richey, Florida 34652
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13001 E. 17th Pl
Aurora, Colorado 80045
303-724-5000
University of Colorado Denver The University of Colorado Denver | Anschutz Medical Campus provides a...
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6410 Rockledge Dr #660
Bethesda, Maryland 20817
(301) 571-0019
Center for Cancer & Blood Disorders Widely recognized for its compassionate, expert care, the Center...
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Birmingham, Alabama 35223
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Bridgeton, Missouri 63044
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Charleston, South Carolina 29425
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Dallas, Texas 75201
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Denver, Colorado 80218
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Detroit, Michigan 48201
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Edmonton, Alberta
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Escondido, California 92025
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Fort Worth, Texas 76104
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Jacksonville, Florida 32256
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7360 W. Deschutes
Kennewick, Washington 99336
509-783-0144
Columbia Basin Hematology and Oncology Our collaboration with Seattle Cancer Care Alliance gives you convenient...
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9280 W. Sunset Road Suite 100
Las Vegas, Nevada 89148
702.952.1251
Comprehensive Cancer Centers of Nevada Comprehensive Cancer Centers of Nevada (CCCN) is the award-winning multidisciplinary...
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Monterey, California 93940
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Newport News, Virginia 23601
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Newport News, Virginia 23606
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Oxnard, CA
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3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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Roanoke, VA
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Round Rock, Texas 78665
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Spokane, Washington 99208
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Tualatin, Oregon 97062
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Washington, District of Columbia 20037
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