Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00376727
Cetuximab in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing cetuximab, molecular diagnostic method and immunologic technique in people with Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.
Trial summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- cetuximab, molecular diagnostic method and immunologic technique
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2004to Dec 2007
- Phase
- Phase 1
- 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
- Signed written informed consent
- Histologically or cytologically proven advanced solid tumors not curable by surgery, radiation therapy or standard chemo-, immuno-, or hormonal therapy. A specific primary cancer need not have been identified (i.e., unknown primary is eligible).
- Patients must have received at least one prior regimen (chemotherapy and/or radiation) for metastatic disease. There is no limit to the number of prior therapies.
- Any prior chemotherapy must have been completed at least 4 weeks prior to start of study therapy. Previous radiation therapy must have been completed at least 2 weeks prior to start of study therapy. All side effects of prior therapy must be resolved prior to the start of study therapy.
- Patients with ZUBROD performance status 0-2 (see Appendix 1).
- Patients must have measurable disease or evaluable disease.
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- Patients must have an estimated survival of at least 3 months.
- Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids for at least 4 weeks.
- Patients >/= 18 years of age.
- Patients of reproductive potential must agree to use an effective contraceptive method while on treatment and for 3 months afterward as the effects of cetuximab on the unborn fetus are unknown.
- Patients must have adequate hematologic function defined as: ANC >/= 1,500/mm3, platelets >/= 100,000/mm3.
- Patients must have adequate hepatic function defined as SGOT </= 3 x institutional UNL and serum bilirubin </= 2.0 mg/dL.
- Patients must have adequate renal function defined as a serum creatinine level </= 1.6 mg/dL or a calculated creatinine clearance of >/= 40 ml/min.
Who cannot join
- Female patients cannot be pregnant or breastfeeding as the effects of cetuximab on the unborn fetus are unknown. Documentation of a negative pregnancy test prior to treatment is required for all women of reproductive potential.
- Uncontrolled intercurrent illness including but not limited to ongoing infection or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Patients with symptomatic brain metastasis or still requiring steroids.
- Patients who have received prior cetuximab therapy, prior therapy with any other drug that targets the EGF receptor (including, but not limited to, Iressa, Tarceva, Herceptin, CI1033, etc.), or prior therapy with a monoclonal antibody.
- Patients who have received prior chemotherapy within 4 weeks or radiation therapy within 2 weeks prior to the start of study therapy.
- Prior hypersensitivity reaction to chimerized or murine monoclonal antibody therapy.
- Patients may not receive any other chemotherapy, radiation therapy, or biologic therapy while on study.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Cancer Center
Sacramento, California, 95817
About this study
Official title: A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of cetuximab in treating patients with advanced solid tumors.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of cetuximab in patients with advanced solid tumors.
Secondary
- Evaluate the safety and tolerability of this drug in these patients.
- Develop a detailed scale for assessment of rash in these patients.
- Investigate potential predictors of response using correlative studies on patient tissue, buccal mucosa, and blood samples.
- Obtain preliminary efficacy data and evaluate the relationship of efficacy to grade of rash.
- Correlate downstream markers (e.g., pMAPK, pAKT, and Ki-67) and the presence of epidermal growth factor receptor (EGFR) polymorphisms with clinical response and/or survival.
- Examine the levels of downstream marker proteins in buccal cells obtained pre- and post-treatment.
- Correlate basal p27 expression levels with response and/or survival.
- Determine if the presence of a K-RAS mutation influences response or survival outcome.
- Correlate the presence or absence of mutant K-RAS tumor DNA shed into patient plasma with response and/or outcome.
- Correlate levels of cytokines and chemokines with rash and clinical response.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive cetuximab IV over 90 minutes once weekly for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo blood and buccal mucosa collection at baseline and prior to courses 2 and 3 of treatment for molecular correlative studies. Archival tumor tissue specimens are also used for molecular correlative studies. Immunologic correlative studies are performed using patient blood samples.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
- Being tested
- cetuximab, molecular diagnostic method, immunologic technique, laboratory biomarker analysis
- Keywords
- unspecified adult solid tumor, protocol specific
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
Also called IMC-C225, Erbitux
Dose level 0: cetuximab 400 mg/m2 week 1, 250 mg/m2 weekly; Dose level 1: cetuximab 400 mg/m2 week 1, 300 mg/m2 weekly; Dose level 2: cetuximab 400 mg/m2 week 1, 350 mg/m2 weekly; Dose level 3: cetuximab 400 mg/m2 week 1, 400 mg/m2 weekly
molecular diagnostic methodGenetic
Tissue and Blood Specimens; IHC Methodology; IHC Scoring; K-RAS Mutation Analysis
immunologic techniqueOther
Peripheral Blood Mononuclear Cells (PBMC)
laboratory biomarker analysisOther
Cetuximab Pharmacodynamics
| Study group | Role | What they receive |
|---|---|---|
| Phase I dose escalation study | Experimental | Not described Receives: Biological: cetuximab; Genetic: molecular diagnostic method; Other: immunologic technique; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of cetuximab
Measured: December 2007
Secondary outcomes (4)
Safety and tolerability of cetuximab
Measured: December 2007
Potential predictors of response using correlative studies
Measured: December 2007
Correlation of efficacy of cetuximab with grade of skin rash
Measured: December 2007
Development of a detailed scale for assessing skin rash
Measured: December 2007
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2006 (estimated)
- Study startDec 2004
- Primary completionNov 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Investigators
- Angela Davies, MD, Study chair, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376727
- Sponsor's protocol ID
- CDR0000506089
- Other IDs
- P30CA093373, UCDCC-165, BMS-CA225027, 200412499, IMCL-8420
- Status last verified
- Mar 2010
- First submitted
- 13 Sep 2006
- Last updated
- 29 Mar 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of the Safety and Tolerability of Four Doses of Cetuximab (C225) in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00376727
- Acronym / sponsor ID
- CDR0000506089
- Keywords
- unspecified adult solid tumor, protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2004
- Primary completion
- Nov 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 15 Sep 2006 (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.
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase I trial is studying the side effects and best dose of cetuximab in treating patients with advanced solid tumors.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of cetuximab in patients with advanced solid tumors.
Secondary
- Evaluate the safety and tolerability of this drug in these patients.
- Develop a detailed scale for assessment of rash in these patients.
- Investigate potential predictors of response using correlative studies on patient tissue, buccal mucosa, and blood samples.
- Obtain preliminary efficacy data and evaluate the relationship of efficacy to grade of rash.
- Correlate downstream markers (e.g., pMAPK, pAKT, and Ki-67) and the presence of epidermal growth factor receptor (EGFR) polymorphisms with clinical response and/or survival.
- Examine the levels of downstream marker proteins in buccal cells obtained pre- and post-treatment.
- Correlate basal p27 expression levels with response and/or survival.
- Determine if the presence of a K-RAS mutation influences response or survival outcome.
- Correlate the presence or absence of mutant K-RAS tumor DNA shed into patient plasma with response and/or outcome.
- Correlate levels of cytokines and chemokines with rash and clinical response.
OUTLINE: This is an open-label, dose-escalation study.
Patients receive cetuximab IV over 90 minutes once weekly for 4 weeks. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
Patients undergo blood and buccal mucosa collection at baseline and prior to courses 2 and 3 of treatment for molecular correlative studies. Archival tumor tissue specimens are also used for molecular correlative studies. Immunologic correlative studies are performed using patient blood samples.
After completion of study treatment, patients are followed periodically for survival.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I dose escalation study | Experimental | Biological: cetuximab, Genetic: molecular diagnostic method, Other: immunologic technique, Other: laboratory biomarker analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Signed written informed consent
- Histologically or cytologically proven advanced solid tumors not curable by surgery, radiation therapy or standard chemo-, immuno-, or hormonal therapy. A specific primary cancer need not have been identified (i.e., unknown primary is eligible).
- Patients must have received at least one prior regimen (chemotherapy and/or radiation) for metastatic disease. There is no limit to the number of prior therapies.
- Any prior chemotherapy must have been completed at least 4 weeks prior to start of study therapy. Previous radiation therapy must have been completed at least 2 weeks prior to start of study therapy. All side effects of prior therapy must be resolved prior to the start of study therapy.
- Patients with ZUBROD performance status 0-2 (see Appendix 1).
Key exclusion criteria (7 listed)
- Female patients cannot be pregnant or breastfeeding as the effects of cetuximab on the unborn fetus are unknown. Documentation of a negative pregnancy test prior to treatment is required for all women of reproductive potential.
- Uncontrolled intercurrent illness including but not limited to ongoing infection or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Patients with symptomatic brain metastasis or still requiring steroids.
- Patients who have received prior cetuximab therapy, prior therapy with any other drug that targets the EGF receptor (including, but not limited to, Iressa, Tarceva, Herceptin, CI1033, etc.), or prior therapy with a monoclonal antibody.
- Patients who have received prior chemotherapy within 4 weeks or radiation therapy within 2 weeks prior to the start of study therapy.
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 |
|---|---|---|
| cetuximabAlso: IMC-C225, ErbituxDose level 0: cetuximab 400 mg/m2 week 1, 250 mg/m2 weekly; Dose level 1: cetuximab 400 mg/m2 week 1, 300 mg/m2 weekly; Dose level 2: cetuximab 400 mg/m2 week 1, 350 mg/m2 weekly; Dose level 3: cetuximab 400 mg/m2 week 1, 400 mg/m2 weekly | Biological | Phase I dose escalation study |
| molecular diagnostic methodTissue and Blood Specimens; IHC Methodology; IHC Scoring; K-RAS Mutation Analysis | Genetic | Phase I dose escalation study |
| immunologic techniquePeripheral Blood Mononuclear Cells (PBMC) | Other | Phase I dose escalation study |
| laboratory biomarker analysisCetuximab Pharmacodynamics | Other | Phase I dose escalation study |
Primary outcome
Maximum tolerated dose of cetuximab
Time frame: December 2007
4 secondary outcomes
Safety and tolerability of cetuximab
Time frame: December 2007
Potential predictors of response using correlative studies
Time frame: December 2007
Correlation of efficacy of cetuximab with grade of skin rash
Time frame: December 2007
Development of a detailed scale for assessing skin rash
Time frame: December 2007
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 29 Mar 2010.
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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.
Angela Davies, MD study chair
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cetuximab, molecular diagnostic method and immunologic technique in people with Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.
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 13 inclusion and 7 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 29 Mar 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
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?
Maximum tolerated dose of cetuximab (time frame: December 2007). 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 29 Mar 2010.