Incurable Metastatic Colorectal CarcinomaPhase 1/2NCT01252628
Phase 1 and 2 Study of PX-866 and Cetuximab
A Phase 1/2 study testing PX-866 (SCCHN), Cetuximab (SCCHN) and PX-866 (CRC) in people with Incurable Metastatic Colorectal Carcinoma and Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck, run by Cascadian Therapeutics Inc. at 40 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Incurable Metastatic Colorectal Carcinoma, Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- PX-866 (SCCHN), Cetuximab (SCCHN) and PX-866 (CRC)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 178 participants
- Where
- 40 sitesin 2 countries
- Study dates
- Dec 2010to Jan 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
40 sites in 2 countries.
40 sites in 2 countries
United States31 sites
Peachtree Hematology-Oncology Consultants
Atlanta, Georgia, 30318
University of Colorado Denver
Aurora, Colorado, 80045
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Birmingham Hematology and Oncology Assocs.
Birmingham, Alabama, 35223
University of Alabama Birmingham
Birmingham, Alabama, 35249
Tufts Medical Center
Boston, Massachusetts, 02111
Saint Louis Cancer Care LLP
Bridgeton, Missouri, 63044
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
Mary Crowley Cancer Center
Dallas, Texas, 75230
Texas Oncology - Baylor Charles A. Sammons
Dallas, Texas, 75246
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Eastern Colorado Health Care System - (Denver VA)
Denver, Colorado, 80220
Karmanos Cancer Institute
Detroit, Michigan, 48201
Southwest Cancer Care
Escondido, California, 92025
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
Texas Oncology - Fort Worth
Fort Worth, Texas, 76104
Integrated Community Oncology Network
Jacksonville, Florida, 32256
Columbia Basin Hematology and Oncology
Kennewick, Washington, 99336
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Advanced Medical Specialties
Miami, Florida, 33176
Monterey Bay Oncology
Monterey, California, 93940
Pasco Pinellas Cancer Center
New Port Richey, Florida, 34652
Peninsula Cancer Institute
Newport News, Virginia, 23601
Virginia Oncology Associates
Newport News, Virginia, 23606
Ventura County Hematology Oncology Specialists
Oxnard, California, 93030
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oncology and Hematology Associates of Southwest Virginia
Roanoke, Virginia, 24014
Texas Oncology - Seton Williamson
Round Rock, Texas, 78665
Medical Oncology Associates
Spokane, Washington, 99208
Northwest Cancer Specialists, P.C.
Tualatin, Oregon, 97062
George Washington University - Medical Faculty Associates
Washington D.C., District of Columbia, 20037
Canada9 sites
Royal Victoria Regional Health Centre
Barrie, Ontario, L4M 6M2
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Northeast Cancer Centre of Health Sciences North
Greater Sudbury, Ontario, P3E 5J1
Hôpital Charles-LeMoyne
Greenfield Park, Quebec, J4V 2H1
Cité de la Santé de Laval
Laval, Quebec, H7M 3L9
London Regional Cancer Program
London, Ontario, N6A 4L6
Maisonneuve-Rosemont Hospital Research Centre
Montreal, Quebec, H1T 2M4
Thunder Bay Regional Health Sciences Centre
Thunder Bay, Ontario, P7B 6V4
British Columbia Cancer Agency - Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: 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).
Read the 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.
- Conditions
- Incurable Metastatic Colorectal Carcinoma, Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
- Being tested
- PX-866 (SCCHN), Cetuximab (SCCHN), PX-866 (CRC), Cetuximab (CRC)
- Keywords
- CRC, SCCHN, PX-866, Cetuximab, ERBITUX, Colon, Head and Neck, Colorectal cancer, Squamous cell carcinoma, PI-3K, PI3 kinase, PI3K
- Medical subject headings
- Recurrence, Colorectal Neoplasms, Carcinoma, Squamous Cell, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PX-866 (SCCHN)Drug
PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.
Cetuximab (SCCHN)Drug
Also called Erbitux
Cetuximab administered weekly on a 21 day cycle, as standard of care in patients.
PX-866 (CRC)Drug
PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle.
Cetuximab (CRC)Drug
Also called Erbitux
Cetuximab administered weekly on a 21 day cycle in patients, as standard of care.
| Study group | Role | What they receive |
|---|---|---|
| PX-866 (SCCHN) | Experimental | Phase 2 (Squamous Cell Carcinoma of the Head and Neck) Receives: Drug: PX-866 (SCCHN); Drug: Cetuximab (SCCHN) |
| Cetuximab (SCCHN) | Active comparator | Phase 2 (Squamous Cell Carcinoma of the Head and Neck) Receives: Drug: Cetuximab (SCCHN) |
| PX-866 (CRC) | Experimental | Phase 2 (Colorectal Carcinoma) Receives: Drug: PX-866 (CRC); Drug: Cetuximab (CRC) |
| Cetuximab (CRC) | Active comparator | Phase 2 (Colorectal Carcinoma) Receives: Drug: Cetuximab (CRC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionNov 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Incurable Metastatic Colorectal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cascadian Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Diana Hausman, MD, Study director, Cascadian Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01252628
- Sponsor's protocol ID
- PX-866-003
- Status last verified
- Jun 2015
- First submitted
- 1 Dec 2010
- Last updated
- 16 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study of PX-866 and Cetuximab
- ClinicalTrials.gov ID
- NCT01252628
- Acronym / sponsor ID
- PX-866-003
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 178 participants (actual)
- Lead sponsor
- Cascadian Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Nov 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 3 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| PX-866 (SCCHN) | Experimental | Drug: PX-866 (SCCHN), Drug: Cetuximab (SCCHN)Phase 2 (Squamous Cell Carcinoma of the Head and Neck) |
| Cetuximab (SCCHN) | Active comparator | Drug: Cetuximab (SCCHN)Phase 2 (Squamous Cell Carcinoma of the Head and Neck) |
| PX-866 (CRC) | Experimental | Drug: PX-866 (CRC), Drug: Cetuximab (CRC)Phase 2 (Colorectal Carcinoma) |
| Cetuximab (CRC) | Active comparator | Drug: Cetuximab (CRC)Phase 2 (Colorectal Carcinoma) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PX-866 (SCCHN)PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle. | Drug | PX-866 (SCCHN) |
| Cetuximab (SCCHN)Also: ErbituxCetuximab administered weekly on a 21 day cycle, as standard of care in patients. | Drug | Cetuximab (SCCHN), PX-866 (SCCHN) |
| PX-866 (CRC)PX-866 administered at the MTD/RD in combination in patients administered weekly on a 21 day cycle. | Drug | PX-866 (CRC) |
| Cetuximab (CRC)Also: ErbituxCetuximab administered weekly on a 21 day cycle in patients, as standard of care. | Drug | Cetuximab (CRC), PX-866 (CRC) |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2018.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Diana Hausman, MD study director
Cascadian Therapeutics Inc.
40 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PX-866 (SCCHN), Cetuximab (SCCHN) and PX-866 (CRC) in people with Incurable Metastatic Colorectal Carcinoma and Incurable Progressive, Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck, run by Cascadian Therapeutics Inc. at 40 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2018.