Erlotinib, Paclitaxel, and Carboplatin Combined With Radiation Therapy for Stage III Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00278148
• Other study ID #: CCF5876
• Secondary ID: P30CA043703CCF-5
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2005
• Est. completion date: February 2011

Study information

• Verified date: July 2020
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• carboplatin
AUC2 weekly x 3 weeks
• Erlotinib
Daily
• paclitaxel
50mg/m2/weekly x 3 weeks

Procedure:
• conventional surgery
conventional surgery

Radiation:
• radiation therapy
150 cGy bid

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Nathan Pennell, MD, PhD	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 weeks after surgery
Primary	Tolerability of Long-term OSI-774 (Phase II)	Number of patients who experienced grade >/= 3 toxicities on maintanance erolotinib (OSI-774)	2 years
Secondary	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.	2 years
Secondary	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.	3 years
Secondary	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	3 years
Secondary	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	2 years
Secondary	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	2 years

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database