Malignant Solid TumourPhase 1NCT00388427
Safety Study Of Cetuximab Plus Dasatinib (BMS-354825) in Treating Advanced Solid Malignancies
A Phase 1 study testing Dasatinib (BMS-354825) and Cetuximab (Erbitux, C225) in people with Malignant Solid Tumour, run by University of Pittsburgh at 1 site in United States.
Trial summary
This is an open-label, safety study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion weekly. Dasatinib will be taken orally, once a day, on a continuous schedule at differing dose levels. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Solid Tumour
- What is being tested?
- Dasatinib (BMS-354825) and Cetuximab (Erbitux, C225)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2007to Feb 2013
- 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
- Histologically or cytologically confirmed solid malignancy which is recurrent or metastatic or resistant to therapy. Patients w/plan of surgery for recurrent disease post cetuximab/dasatinib are eligible providing that they receive at least 2 cycles of therapy and provide baseline and post-treatment tumor tissue for correlatives.
- Any number of prior regimens but no prior EGFR or src inhibitors.
- Age greater or equal to 18 years.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
- Life expectancy greater than 12 weeks.
- Patients must have normal organ and marrow function:
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- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
- creatinine up to 1.5 x normal institutional limits
- Ability to understand and the willingness to sign a written informed Consent document.
- No concomitant medication that are CYP3A4 inducers or potent inhibitors and should not take proton pump inhibitors and H2 antagonists in the first cycle of therapy and should try to avoid taking proton pump inhibitors and H2 antagonists during rest of treatment period.
- Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. All WOCBP must have a negative pregnancy test prior to first receiving investigational product.
Who cannot join
- Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Any other concurrent investigational agents.
- Patients w/ untreated brain metastases. However, patients who have stable brain disease (should be off corticosteroids) at least 4 weeks after completion of appropriate therapy are eligible.
- History of allergic reaction to monoclonal antibodies.
- Inability to swallow oral medications unless patients use a feeding tube.
- Uncontrolled angina or hypertension or any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes).
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- Prolonged QTc interval on pre-entry electrocardiogram (greater than 450 msec) on both the Fridericia and Bazett's correction.
- Diagnosed or suspected congenital long QT syndrome.
- Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
- Any other uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements.
- History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease), diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies).
- HIV-positive patients receiving combination antiretroviral therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Cancer Institute - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase I Study of Cetuximab Plus Dasatinib (BMS-354825) in Advanced Solid Malignancies
This is an open-label, safety study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion weekly. Dasatinib will be taken orally, once a day, on a continuous schedule at differing dose levels. The primary objective of this study is to determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors.
Read the detailed description
This is an open-label, phase I study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion on a standard dose and schedule (weekly, with the first dose at 400 mg/m2 and all subsequent weekly doses at 250 mg/m2). Dasatinib will be administered orally on a continuous schedule at the following dose levels: 100 mg QD (once a day), 150 mg QD, and 200 mg QD. Three to six patients will be enrolled at each dose level, and the final recommended phase II cohort will be expanded to include up to 12 additional patients. The doses will be escalated in successive cohorts of patients. On cycle 1, dasatinib administration will start one day prior to cetuximab administration. One cycle will be defined as 21 days, and cycles will continue until progression of disease or intolerable toxicities occur. Peripheral blood samples and pharmacokinetic blood samples will be taken on days 0, 1, 15, and 16 of Cycle 1 only. In patients with accessible tumor that give consent, patients will undergo a baseline tumor biopsy and a repeat biopsy after 14-21 days of the first cycle.
- Conditions
- Malignant Solid Tumour
- Being tested
- Dasatinib (BMS-354825), Cetuximab (Erbitux, C225)
- Keywords
- advanced cancer, solid tumor, solid malignancies, phase I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dasatinib (BMS-354825)Drug
100 mg, 150 mg, or 200 mg per dose escalation schedule; continuous oral dosing on Days 1-21 of each 21-day cycle until progression or unacceptable toxicity develops.
Cetuximab (Erbitux, C225)Drug
Loading dose of IV 400 mg/m^2 on Day 1 of Cycle 1; IV 250 mg/m^2 weekly thereafter each 21-day cycle until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Advanced Solid Malignancies | Other | Not described Receives: Drug: Dasatinib (BMS-354825); Drug: Cetuximab (Erbitux, C225) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors
Measured: Anticipated completion date December 2008
Secondary outcomes (5)
To determine the objective response rate and overall survival in patients enrolled in the study
Measured: Anticipated completion date December 2008
To evaluate tissue biomarkers that relate to EGFR and Src signaling pathways on baseline tumor tissue and to study their modulation with cetuximab/dasatinib on post-treatment tumor tissue
Measured: Anticipated completion date December 2008
To measure Src in peripheral blood mononuclear cells (PBMCs) before and after therapy
Measured: Anticipated completion date December 2008
To evaluate EGFR gene copy number by FISH on baseline tumor tissue
Measured: Anticipated completion date December 2008
To determine pharmacokinetic parameters of dasatinib in patients with and without feeding tubes
Measured: Anticipated completion date December 2008
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2006 (estimated)
- Study startJun 2007
- Primary completionJul 2009
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Solid TumourStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Edward Chu, MD, University of Pittsburgh
- Investigators
- Edward Chu, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00388427
- Sponsor's protocol ID
- 06-038
- Other IDs
- CA180049
- Status last verified
- Jan 2014
- First submitted
- 13 Oct 2006
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Cetuximab Plus Dasatinib (BMS-354825) in Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT00388427
- Acronym / sponsor ID
- 06-038
- Conditions
- Malignant Solid Tumour
- Keywords
- advanced cancer, solid tumor, solid malignancies, phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Jun 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 16 Oct 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.
This is an open-label, safety study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion weekly. Dasatinib will be taken orally, once a day, on a continuous schedule at differing dose levels. The primary objective of this study is to determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors.
Detailed description
This is an open-label, phase I study of cetuximab and differing dose levels of dasatinib in adult patients with advanced solid malignancies. Cetuximab will be administered as an intravenous infusion on a standard dose and schedule (weekly, with the first dose at 400 mg/m2 and all subsequent weekly doses at 250 mg/m2). Dasatinib will be administered orally on a continuous schedule at the following dose levels: 100 mg QD (once a day), 150 mg QD, and 200 mg QD. Three to six patients will be enrolled at each dose level, and the final recommended phase II cohort will be expanded to include up to 12 additional patients. The doses will be escalated in successive cohorts of patients. On cycle 1, dasatinib administration will start one day prior to cetuximab administration. One cycle will be defined as 21 days, and cycles will continue until progression of disease or intolerable toxicities occur. Peripheral blood samples and pharmacokinetic blood samples will be taken on days 0, 1, 15, and 16 of Cycle 1 only. In patients with accessible tumor that give consent, patients will undergo a baseline tumor biopsy and a repeat biopsy after 14-21 days of the first cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Advanced Solid Malignancies | Other | Drug: Dasatinib (BMS-354825), Drug: Cetuximab (Erbitux, C225) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histologically or cytologically confirmed solid malignancy which is recurrent or metastatic or resistant to therapy. Patients w/plan of surgery for recurrent disease post cetuximab/dasatinib are eligible providing that they receive at least 2 cycles of therapy and provide baseline and post-treatment tumor tissue for correlatives.
- Any number of prior regimens but no prior EGFR or src inhibitors.
- Age greater or equal to 18 years.
- ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
- Life expectancy greater than 12 weeks.
Key exclusion criteria (12 listed)
- Chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Any other concurrent investigational agents.
- Patients w/ untreated brain metastases. However, patients who have stable brain disease (should be off corticosteroids) at least 4 weeks after completion of appropriate therapy are eligible.
- History of allergic reaction to monoclonal antibodies.
- Inability to swallow oral medications unless patients use a feeding tube.
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 |
|---|---|---|
| Dasatinib (BMS-354825)100 mg, 150 mg, or 200 mg per dose escalation schedule; continuous oral dosing on Days 1-21 of each 21-day cycle until progression or unacceptable toxicity develops. | Drug | Advanced Solid Malignancies |
| Cetuximab (Erbitux, C225)Loading dose of IV 400 mg/m^2 on Day 1 of Cycle 1; IV 250 mg/m^2 weekly thereafter each 21-day cycle until progression or unacceptable toxicity develops. | Drug | Advanced Solid Malignancies |
Primary outcome
To determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors
Time frame: Anticipated completion date December 2008
5 secondary outcomes
To determine the objective response rate and overall survival in patients enrolled in the study
Time frame: Anticipated completion date December 2008
To evaluate tissue biomarkers that relate to EGFR and Src signaling pathways on baseline tumor tissue and to study their modulation with cetuximab/dasatinib on post-treatment tumor tissue
Time frame: Anticipated completion date December 2008
To measure Src in peripheral blood mononuclear cells (PBMCs) before and after therapy
Time frame: Anticipated completion date December 2008
To evaluate EGFR gene copy number by FISH on baseline tumor tissue
Time frame: Anticipated completion date December 2008
To determine pharmacokinetic parameters of dasatinib in patients with and without feeding tubes
Time frame: Anticipated completion date December 2008
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 28 May 2015.
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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.
Edward Chu, MD principal investigator
University of Pittsburgh
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 Dasatinib (BMS-354825) and Cetuximab (Erbitux, C225) in people with Malignant Solid Tumour, run by University of Pittsburgh 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 15 inclusion and 12 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 28 May 2015. 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?
To determine the toxicities and the maximum tolerated doses of dasatinib when combined with cetuximab for the treatment of advanced solid tumors (time frame: Anticipated completion date December 2008). 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 28 May 2015.