Lung CancerPhase 1/2NCT00408499
Erlotinib and Cetuximab in Treating Patients With Advanced Solid Tumors With Emphasis on Non-Small Cell Lung Cancer
A Phase 1/2 study testing cetuximab and erlotinib in people with Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.
Trial summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- cetuximab and erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Jan 2013
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- For the phase I portion of the study (completed 10/05/08), patients must have cytologically or histologically proven advanced solid tumors for which there is no standard effective therapy available.
- Any number of prior chemotherapy regimens are allowed for the both the Phase I and Phase II portions
- For the phase II portion patients must have cytologically or histologically proven selected stage IIIB (pleural effusion) or IV NSCLC. Patients with NSCLC that have progressed or recurred after first-line therapy for stage IIIA or IIIB may also be considered.
- Patients must have measurable disease by RECIST criteria for the Phase II portion. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy. Patients with evaluable disease (bone metastases, pleural fluid, ascites, etc.) may be included in the phase I portion of the trial (completed 10/08/08).
- Must be 18 years of age or older.
- Patients must have a performance status of 0 -2.
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- Patients must have an estimated survival of at least 3 months.
- Any prior chemotherapy must have been completed at least 4 weeks prior to start of treatment. For prior mitomycin chemotherapy a 6-week interval is required. Prior radiation must have been completed at least 2 weeks prior to start of therapy. Patients must have recovered from acute reversible medically significant side effects of prior chemotherapy regimens or radiotherapy to NCI-CTC < grade 1 (excluding alopecia). Prior herceptin is allowed.
- Patients must have adequate renal function as documented by a serum creatinine < 1.5 mg/dl or a calculated creatinine clearance of > 45 ml/min (see protocol Appendix D for formula for calculating creatinine clearance).
- Patients must have adequate liver function as documented by serum bilirubin < 1.5 x ULN. AST must be < 2.5 x institutional upper limit of normal.
- Patients must have a pretreatment granulocyte count of >1500/mm3 and platelet count of >100 000/mm3.
- Patients with asymptomatic treated brain metastasis (surgical resection or radiotherapy) may be included if they are neurologically stable and have been off steroids and anticonvulsants for at least 2 weeks.
- All patients must give voluntary written informed consent.
- Patients must be able to take and retain oral medication.
- Documentation of a negative serum pregnancy test.
- Patients on coumadin should have their INR monitored at least once per week or more frequently depending on the investigator's judgment. There have been some case reports of increased INR when coumadin is co-administered with erlotinib.
Who cannot join
- Patients who have received erlotinib, cetuximab, or any other EGFR-directed therapy (excluding herceptin).
- Patients with symptomatic brain metastasis or still requiring steroids and anti-convulsants may not be included.
- For the phase II portion of the study, no other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, and any other cancer from which the patient has been disease-free for over five years
- Patients with acute hepatitis or known HIV.
- Patients with active or uncontrolled infection.
- Patients with significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
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- Patients with prior severe infusion reaction to a monoclonal antibody.
- Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
- Pregnant or breastfeeding females as the effects of these drugs on the unborn fetus are unknown.
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: Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving erlotinib together with cetuximab may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib and cetuximab and to see how well they work in treating patients with advanced solid tumors or progressive or recurrent stage III or stage IV non-small cell lung cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the safety and feasibility of erlotinib hydrochloride and cetuximab in patients with advanced solid tumors. (Phase I)
- Determine the efficacy of this regimen, in terms of objective tumor response rate, in patients with advanced non-small cell lung cancer (NSCLC) pre-treated with platinum. (Phase II)
Secondary
- Determine the maximum tolerated dose of this regimen in these patients. (Phase I)
- Determine the efficacy of this regimen, in terms of response rate, in these patients. (Phase I)
- Determine the progression-free and overall survival of patients treated with this regimen. (Phase II)
- Determine the frequency and severity of toxicities of this regimen in these patients. (Phase II)
- Determine epidermal growth factor receptor (EGFR) and K-RAS mutation status. (Phase II)
- Evaluate EGFR protein expression and protein expression of downstream markers (e.g., pMAPK, pAKT, p27, and Ki-67). (Phase II)
- Evaluate the levels of marker proteins (e.g., pMAPK, pAKT, p27, and Ki-67) in buccal cells. (Phase II)
- Determine gene copy number by EGFR fluorescent in situ hybridization (FISH). (Phase II)
- Identify EGFR polymorphisms by analysis of genomic DNA from peripheral blood mononuclear cells. (Phase II)
- Determine if the continued presence or absence of mutant K-RAS tumor DNA correlates with response and/or outcome. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study.
- Phase I: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
- Phase II: Patients receive erlotinib hydrochloride and cetuximab at the MTD determined in phase I.
Blood and buccal samples are acquired from patients at baseline and prior to courses 2 and 3. Samples are examined by fluorescent in situ hybridization (FISH), immunohistochemistry, polymorphism analysis, and protein expression assays to assess molecular markers (epidermal growth factor receptor, K-RAS, pMAPK, pAKT, p27 and Ki-67) for biologic effects and predictive response.
After completion of phase I treatment, patients are followed for 30 days or until all toxicities resolve. After completion of phase II treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study
- Keywords
- unspecified adult solid tumor, protocol specific, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabDrug
Also called Erbitux
Cetuximab will be administered intravenously weekly at the maximum tolerated dose (determined in Phase I portion of the study) on a 28 day cycle. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.
erlotinibDrug
Also called Tarceva
Erlotinib will be taken by mouth daily on a 28 day cycle. It is in tablet form. The dose will be determined in Phase I portion of the study. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib + Cetuximab | Experimental | Daily erlotinib combined with weekly cetuximab Receives: Drug: cetuximab; Drug: erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Experiencing a DLT
Patients will be followed during cycle 1 for the occurrence of a protocol defined dose limiting toxicity
Measured: baseline through cycle 1 of treatment
Number of Patients Correlated With Best Overall Response.
To determine the efficacy, as measured by objective tumor response rate (RICIST criteria), of daily oral erlotinib and weekly intravenous cetuximab in patients with advanced NSCLC. Best overall response per patient will be reported below.
Measured: Every two cycles from first dose to last dose of study drugs
Secondary outcomes (1)
Patient Outcome
In the Phase II portion of the study, patients will be followed for both disease free progression by capturing disease progression date and for over all survival by capturing death date.
Measured: Patients will be followed until death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2006 (estimated)
- Study startAug 2006
- Primary completionApr 2009
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David R. Gandara, MD, Study chair, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00408499
- Sponsor's protocol ID
- CDR0000517090
- Other IDs
- P30CA093373, UCDCC-177, BMS-4608, BMS-CA225-261
- Status last verified
- Jan 2017
- First submitted
- 6 Dec 2006
- Last updated
- 8 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT00408499
- Acronym / sponsor ID
- CDR0000517090
- Keywords
- unspecified adult solid tumor, protocol specific, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2006
- Primary completion
- Apr 2009 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 7 Dec 2006 (estimated)
- Results
- Posted 8 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Giving erlotinib together with cetuximab may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib and cetuximab and to see how well they work in treating patients with advanced solid tumors or progressive or recurrent stage III or stage IV non-small cell lung cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the safety and feasibility of erlotinib hydrochloride and cetuximab in patients with advanced solid tumors. (Phase I)
- Determine the efficacy of this regimen, in terms of objective tumor response rate, in patients with advanced non-small cell lung cancer (NSCLC) pre-treated with platinum. (Phase II)
Secondary
- Determine the maximum tolerated dose of this regimen in these patients. (Phase I)
- Determine the efficacy of this regimen, in terms of response rate, in these patients. (Phase I)
- Determine the progression-free and overall survival of patients treated with this regimen. (Phase II)
- Determine the frequency and severity of toxicities of this regimen in these patients. (Phase II)
- Determine epidermal growth factor receptor (EGFR) and K-RAS mutation status. (Phase II)
- Evaluate EGFR protein expression and protein expression of downstream markers (e.g., pMAPK, pAKT, p27, and Ki-67). (Phase II)
- Evaluate the levels of marker proteins (e.g., pMAPK, pAKT, p27, and Ki-67) in buccal cells. (Phase II)
- Determine gene copy number by EGFR fluorescent in situ hybridization (FISH). (Phase II)
- Identify EGFR polymorphisms by analysis of genomic DNA from peripheral blood mononuclear cells. (Phase II)
- Determine if the continued presence or absence of mutant K-RAS tumor DNA correlates with response and/or outcome. (Phase II)
OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study.
- Phase I: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.
- Phase II: Patients receive erlotinib hydrochloride and cetuximab at the MTD determined in phase I.
Blood and buccal samples are acquired from patients at baseline and prior to courses 2 and 3. Samples are examined by fluorescent in situ hybridization (FISH), immunohistochemistry, polymorphism analysis, and protein expression assays to assess molecular markers (epidermal growth factor receptor, K-RAS, pMAPK, pAKT, p27 and Ki-67) for biologic effects and predictive response.
After completion of phase I treatment, patients are followed for 30 days or until all toxicities resolve. After completion of phase II treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib + Cetuximab | Experimental | Drug: cetuximab, Drug: erlotinibDaily erlotinib combined with weekly cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- For the phase I portion of the study (completed 10/05/08), patients must have cytologically or histologically proven advanced solid tumors for which there is no standard effective therapy available.
- Any number of prior chemotherapy regimens are allowed for the both the Phase I and Phase II portions
- For the phase II portion patients must have cytologically or histologically proven selected stage IIIB (pleural effusion) or IV NSCLC. Patients with NSCLC that have progressed or recurred after first-line therapy for stage IIIA or IIIB may also be considered.
- Patients must have measurable disease by RECIST criteria for the Phase II portion. Disease in previously irradiated sites is considered measurable if there is clear disease progression following radiation therapy. Patients with evaluable disease (bone metastases, pleural fluid, ascites, etc.) may be included in the phase I portion of the trial (completed 10/08/08).
- Must be 18 years of age or older.
Key exclusion criteria (9 listed)
- Patients who have received erlotinib, cetuximab, or any other EGFR-directed therapy (excluding herceptin).
- Patients with symptomatic brain metastasis or still requiring steroids and anti-convulsants may not be included.
- For the phase II portion of the study, no other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, and any other cancer from which the patient has been disease-free for over five years
- Patients with acute hepatitis or known HIV.
- Patients with active or uncontrolled infection.
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: ErbituxCetuximab will be administered intravenously weekly at the maximum tolerated dose (determined in Phase I portion of the study) on a 28 day cycle. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy. | Drug | Erlotinib + Cetuximab |
| erlotinibAlso: TarcevaErlotinib will be taken by mouth daily on a 28 day cycle. It is in tablet form. The dose will be determined in Phase I portion of the study. Participants will be in this study for at least 2 cycles (8 weeks). If the evaluations show that this treatment has been effective against the participant's cancer, he/she will continue the therapy. | Drug | Erlotinib + Cetuximab |
Primary outcome
Number of Patients Experiencing a DLT
Time frame: baseline through cycle 1 of treatment
Patients will be followed during cycle 1 for the occurrence of a protocol defined dose limiting toxicity
Number of Patients Correlated With Best Overall Response.
Time frame: Every two cycles from first dose to last dose of study drugs
To determine the efficacy, as measured by objective tumor response rate (RICIST criteria), of daily oral erlotinib and weekly intravenous cetuximab in patients with advanced NSCLC. Best overall response per patient will be reported below.
1 secondary outcome
Patient Outcome
Time frame: Patients will be followed until death
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
David R. Gandara, 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 1/2 study testing cetuximab and erlotinib in people with Lung Cancer and 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 16 inclusion and 9 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 8 May 2017. 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 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?
Yes. Results are posted in the registry (first posted 8 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients Experiencing a DLT (time frame: baseline through cycle 1 of treatment). The study lists 2 primary outcomes in all. 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 8 May 2017.