Lung CancerPhase 1/2NCT00278148
Erlotinib, Paclitaxel, and Carboplatin Combined With Radiation Therapy for Stage III Non-Small Cell Lung Cancer
A Phase 1/2 study testing carboplatin, Erlotinib and paclitaxel in people with Lung Cancer, run by Nathan Pennell, MD, PhD 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. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- carboplatin, Erlotinib and paclitaxel
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Feb 2011
- 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
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed non-small cell lung cancer
- Surgically determined stage IIIA or IIIB disease
- Histology from an involved mediastinal or supraclavicular lymph nodes alone will be allowed if a separate distal primary lesion is clearly evident on radiographs
- Histological or cytological proof of mediastinal nodal involvement by mediastinoscopy, Chamberlain procedure, thoracoscopy, thoracotomy, or CT-guided biopsy is required except for cases of paralysis of left true vocal cord with separate left lung primary distinct from enlarged nodes > 1 cm in the anterior-posterior window seen on the CT scan
- Patients with N3 or T4 status must be evaluated and deemed potentially resectable after induction chemotherapy and radiation therapy
- Measurable and evaluable disease
- No malignant pleural effusion except for effusion visible only on CT scan and deemed too small to tap
- No pericardial effusion
- No small or mixed small cell/non-small cell lung cancer
- No massive lesions requiring radiation to the entire lung
- No metastatic cancer to the lungs
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- WBC ≥ 3,000/mm^3
- Platelet count > 100,000/mm^3
- Serum creatinine ≤ 2.0 mg/dL
- Alkaline phosphatase, AST, and ALT < 2 times upper limit of normal
- Albumin > 3.0 g/dL
- Serum bilirubin < 1.5 mg/dL
- Adequate pulmonary function
- No clinical evidence of another uncontrolled malignancy
- No requirement for urgent therapy for severe local symptoms such as post-obstructive pneumonia
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiation therapy, or immunotherapy for lung cancer
- No prior surgery to treat the cancer
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
Official title: A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib, paclitaxel, and carboplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I/II trial is studying the best dose of erlotinib and the side effects of erlotinib, paclitaxel, and carboplatin when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for stage III non-small cell lung cancer.
Read the detailed description
OBJECTIVES:
Primary
- Assess the safety and feasibility of erlotinib hydrochloride, paclitaxel, and carboplatin in combination with accelerated hyperfractionated radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer.
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients.
- Assess the safety and tolerability of long-term maintenance erlotinib hydrochloride after completion of adjuvant chemoradiotherapy in these patients.
Secondary
- Evaluate the clinical and pathological response rate in these patients after neoadjuvant erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy.
- Assess the impact of erlotinib hydrochloride on disease-free survival, overall survival, locoregional control, and distant metastatic control in these patients.
OUTLINE: This is an open-label, phase I dose-escalation study of erlotinib hydrochloride followed by a non-randomized phase II study.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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.
- Phase I:
- Neoadjuvant chemoradiotherapy: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15 in the absence of disease progression or unacceptable toxicity. Patients concurrently undergo radiotherapy twice daily on days 1-5 and 8-12. Patients with complete response, partial response, or stable disease proceed to surgery. Patients who develop a medical contraindication to surgery (i.e., medically unresectable) receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as above within 2 weeks after completion of neoadjuvant chemoradiotherapy.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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.
- Surgery: Within 4 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection and then proceed to adjuvant chemoradiotherapy.
- Adjuvant chemoradiotherapy: Within 6-8 weeks after surgery, patients receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as in neoadjuvant chemoradiotherapy.
- Maintenance therapy: All patients receive oral erlotinib hydrochloride once daily for 2 years in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive treatment as in phase I with erlotinib hydrochloride at the MTD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
- Conditions
- Lung Cancer
- Being tested
- carboplatin, Erlotinib, paclitaxel, conventional surgery, radiation therapy
- Keywords
- stage IIIA non-small cell lung cancer, stage IIIB 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.
carboplatinDrug
Also called Carbo
AUC2 weekly x 3 weeks
ErlotinibDrug
Also called OSI-774, Tarceva
Daily
paclitaxelDrug
50mg/m2/weekly x 3 weeks
conventional surgeryProcedure or surgery
conventional surgery
radiation therapyRadiation
150 cGy bid
| Study group | Role | What they receive |
|---|---|---|
| Dose Level A | Experimental | Erlotinib, Paclitaxel, and Carboplatin with Radiation
Dose Level A: 50 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin Receives: Drug: carboplatin; Drug: Erlotinib; Drug: paclitaxel; Procedure: conventional surgery; Radiation: radiation therapy |
| Dose Level B | Experimental | Erlotinib, Paclitaxel, and Carboplatin with Radiation
Dose Level B: 100 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin Receives: Drug: carboplatin; Drug: Erlotinib; Drug: paclitaxel; Procedure: conventional surgery; Radiation: radiation therapy |
| Dose Level C | Experimental | Erlotinib, Paclitaxel, and Carboplatin with Radiation
Dose Level C: 150 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin Receives: Drug: carboplatin; Drug: Erlotinib; Drug: paclitaxel; Procedure: conventional surgery; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)
The Phase I portion of this study is to determine the Maximum Tolerated Dose (MTD) of combining OSI-774 with the paclitaxel-carboplatin chemoradiation protocol and to assess the safety and feasiblity of this combination.
Measured: 2 weeks after surgery
Tolerability of Long-term OSI-774 (Phase II)
Number of patients who experienced grade >/= 3 toxicities on maintanance erolotinib (OSI-774)
Measured: 2 years
Secondary outcomes (5)
Pathological Complete Response Rate
Number of participants with an pathological complete response rate using the RECIST criteria.
Complete response: Disappearance of all measurable and evaluable disease Partial response: A 30% or greater decline in the sum of the longest diameter of target lesions compared to the baseline measurement.
Progressive disease: A 20% or greater increase in the sum of the longest diameter of the target lesions compared to the baseline.
Stable disease: Disease that did not meet the criteria for a CR / PR or progressive disease.
Measured: 2 years
Overall Survival
Percent of participants still alive from the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up.
Measured: 3 years
Progression Free Survival (PFS)
Months from the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up
Measured: 3 years
Locoregional Control
Estimated by the Kaplan-Meier method and summarized at various follow-up points as the number of patients remaining at risk, the event estimate, standard error, and median.From the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up, assessed up to 2 years
Measured: 2 years
Distant Control
Estimated by the Kaplan-Meier method and summarized at various follow-up points as the number of patients remaining at risk, the event estimate, standard error, and median.From the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up, assessed up to 2 years
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2006 (estimated)
- Study startOct 2005
- Primary completionFeb 2011
- Study completionFeb 2011
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.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Pennell, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Nathan Pennell, MD, PhD, Case Comprehensive Cancer Center
- Investigators
- Nathan Pennell, MD, Study chair, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00278148
- Sponsor's protocol ID
- CCF5876
- Other IDs
- P30CA043703, CCF-5876
- Status last verified
- Jul 2020
- First submitted
- 16 Jan 2006
- Last updated
- 20 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00278148
- Acronym / sponsor ID
- CCF5876
- Conditions
- Lung Cancer
- Keywords
- stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Nathan Pennell, MD, PhDUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2005
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 18 Jan 2006 (estimated)
- Results
- Posted 20 Jul 2020
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. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib, paclitaxel, and carboplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I/II trial is studying the best dose of erlotinib and the side effects of erlotinib, paclitaxel, and carboplatin when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for stage III non-small cell lung cancer.
Detailed description
OBJECTIVES:
Primary
- Assess the safety and feasibility of erlotinib hydrochloride, paclitaxel, and carboplatin in combination with accelerated hyperfractionated radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer.
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients.
- Assess the safety and tolerability of long-term maintenance erlotinib hydrochloride after completion of adjuvant chemoradiotherapy in these patients.
Secondary
- Evaluate the clinical and pathological response rate in these patients after neoadjuvant erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy.
- Assess the impact of erlotinib hydrochloride on disease-free survival, overall survival, locoregional control, and distant metastatic control in these patients.
OUTLINE: This is an open-label, phase I dose-escalation study of erlotinib hydrochloride followed by a non-randomized phase II study.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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.
- Phase I:
- Neoadjuvant chemoradiotherapy: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15 in the absence of disease progression or unacceptable toxicity. Patients concurrently undergo radiotherapy twice daily on days 1-5 and 8-12. Patients with complete response, partial response, or stable disease proceed to surgery. Patients who develop a medical contraindication to surgery (i.e., medically unresectable) receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as above within 2 weeks after completion of neoadjuvant chemoradiotherapy.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride 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.
- Surgery: Within 4 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo surgical resection and then proceed to adjuvant chemoradiotherapy.
- Adjuvant chemoradiotherapy: Within 6-8 weeks after surgery, patients receive a second course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as in neoadjuvant chemoradiotherapy.
- Maintenance therapy: All patients receive oral erlotinib hydrochloride once daily for 2 years in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive treatment as in phase I with erlotinib hydrochloride at the MTD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level A | Experimental | Drug: carboplatin, Drug: Erlotinib, Drug: paclitaxel, Procedure: conventional surgery, Radiation: radiation therapyErlotinib, Paclitaxel, and Carboplatin with Radiation Dose Level A: 50 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin |
| Dose Level B | Experimental | Drug: carboplatin, Drug: Erlotinib, Drug: paclitaxel, Procedure: conventional surgery, Radiation: radiation therapyErlotinib, Paclitaxel, and Carboplatin with Radiation Dose Level B: 100 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin |
| Dose Level C | Experimental | Drug: carboplatin, Drug: Erlotinib, Drug: paclitaxel, Procedure: conventional surgery, Radiation: radiation therapyErlotinib, Paclitaxel, and Carboplatin with Radiation Dose Level C: 150 mg OSI-774/50 mg/m2 Paclitaxel/2 AUC Carboplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| carboplatinAlso: CarboAUC2 weekly x 3 weeks | Drug | Dose Level A, Dose Level B, Dose Level C |
| ErlotinibAlso: OSI-774, TarcevaDaily | Drug | Dose Level A, Dose Level B, Dose Level C |
| paclitaxel50mg/m2/weekly x 3 weeks | Drug | Dose Level A, Dose Level B, Dose Level C |
| conventional surgeryconventional surgery | Procedure or surgery | Dose Level A, Dose Level B, Dose Level C |
| radiation therapy150 cGy bid | Radiation | Dose Level A, Dose Level B, Dose Level C |
Primary outcome
Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)
Time frame: 2 weeks after surgery
The Phase I portion of this study is to determine the Maximum Tolerated Dose (MTD) of combining OSI-774 with the paclitaxel-carboplatin chemoradiation protocol and to assess the safety and feasiblity of this combination.
Tolerability of Long-term OSI-774 (Phase II)
Time frame: 2 years
Number of patients who experienced grade >/= 3 toxicities on maintanance erolotinib (OSI-774)
5 secondary outcomes
Pathological Complete Response Rate
Time frame: 2 years
Overall Survival
Time frame: 3 years
Progression Free Survival (PFS)
Time frame: 3 years
Locoregional Control
Time frame: 2 years
Distant Control
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Clinical trial summary from the National Cancer Institute's PDQ® databaseLink provided by the sponsor.
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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.
Nathan Pennell, MD study chair
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
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 carboplatin, Erlotinib and paclitaxel in people with Lung Cancer, run by Nathan Pennell, MD, PhD 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?
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 20 Jul 2020. 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 20 Jul 2020). 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?
Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I) (time frame: 2 weeks after surgery). 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 20 Jul 2020.