Pemetrexed Disodium and Cisplatin in Treating Patients Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

NCT ID: NCT00248495

Last Updated: 2017-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-08
• Study Completion Date: 2017-04-05

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving them before and after surgery may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and cisplatin before and after surgery works in treating patients with stage I, stage II, or stage III non-small cell lung cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine the pathologic complete response in patients with stage IB-IIIB non-small cell lung cancer treated with neoadjuvant chemotherapy comprising pemetrexed disodium and cisplatin followed by surgery and adjuvant pemetrexed disodium and cisplatin.

Secondary

• Determine the adverse events of this regimen in these patients.
• Determine the overall and disease-free survival of patients treated with this regimen.
• Correlate response with the presence or absence of ERCC1 and DHFR, thymidylate synthase, DPD, and GARFT in patients treated with this regimen.
• Correlate the fragile site on chromosome 12 within the SMRT gene with metastasis after definitive treatment with this regimen in these patients.

OUTLINE:

• Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over approximately 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients are then evaluated for disease resectability. Patients with no evidence of disease progression proceed to thoracotomy within the next 28-48 days.
• Thoracotomy: Patients found to have unresectable disease during thoracotomy receive further treatment off study. Patients with resectable disease undergo complete surgical resection of the tumor. Forty to eighty days later, patients proceed to adjuvant chemotherapy.
• Adjuvant chemotherapy: Patients receive pemetrexed disodium and cisplatin as before for 2 courses.

Patients with progressive disease after completion of neoadjuvant chemotherapy are followed every 6 months. All other patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study over 6.5 years.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant chemotherapy

Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over approximately 1 hour on day 1. Treatment repeats every 21 days for 3 courses

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

Given IV

pemetrexed disodium

Intervention Type: DRUG

Given IV

adjuvant therapy

Intervention Type: PROCEDURE

Metastasis prevention/control

conventional surgery

Intervention Type: PROCEDURE

Undergoing tissue removal

neoadjuvant therapy

Intervention Type: PROCEDURE

Tumor Reduction

Interventions

cisplatin

Given IV

Intervention Type: DRUG

pemetrexed disodium

Given IV

Intervention Type: DRUG

adjuvant therapy

Metastasis prevention/control

Intervention Type: PROCEDURE

conventional surgery

Undergoing tissue removal

Intervention Type: PROCEDURE

neoadjuvant therapy

Tumor Reduction

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Microscopically confirmed non-small cell lung cancer

• Stage IB (T2, N0, M0), IIA (T1, N1, M0), IIB (T2, N1, M0 or T3, N0, M0), or IIIA (T1-3, N1-2, M0) disease
• Satellite lesions in one lobe (T4) (stage IIIB) allowed
• Meets 1 of the following criteria:

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 10 mm in the longest diameter
• Evaluable disease, defined as lesions on chest CT scan that are not measurable (e.g., ill-defined masses or mediastinal or hilar adenopathy)
• No metastatic disease except peribronchial/hilar lymph nodes (N1) or ipsilateral/subcarinal mediastinal lymph nodes (N2)

• No N3 lymph nodes (e.g., contralateral mediastinal/hilar or supraclavicular/scalene) by CT scan or positron emission tomography (PET) scan AND mediastinoscopy
• No T4 primary tumor (e.g., mediastinal invasion)
• No malignant pleural effusion

• Nonmalignant effusions (i.e., negative cytology, non-bloody, and transudate) allowed
• Effusions visible only by CT scan and not large enough for safe thoracentesis allowed
• No exudative effusion, defined by 1 of the following criteria:

• Pleural fluid protein:serum protein ratio > 0.5
• Pleural fluid lactic dehydrogenase (LDH):serum LDH ratio ≥ 0.6
• Pleural fluid LDH > 200 IU/L
• No more than 1 area of fludeoxyglucose (FDG) uptake outside the area of the primary lung tumor OR evidence of malignant pleural disease as evidenced by pleural nodules by PET scan

• Single areas of FDG uptake will be further evaluated (e.g., by biopsy) for metastatic disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• SGOT or SGPT ≤ 1.5 times upper limit of normal

Renal

• Creatinine clearance ≥ 45 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No other active malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for lung cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for lung cancer

Surgery

• No prior surgery for lung cancer
• At least 12 weeks since prior major surgery to the chest and abdomen

Other

• No concurrent aspirin or other nonsteroidal anti-inflammatory drugs for ≥ 2 days before (5 days for drugs with a long half-life [e.g., naproxen, piraoxicam, difunisal, nabumetone, rofecoxib, or celecoxib] or 8 days for long acting agents), during, and for 2 days after completion of each pemetrexed disodium administration
• No concurrent participation in another study involving chemotherapy or radiotherapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Grace K. Dy, MD

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Other Identifiers

RPCI I-31104

Identifier Type: -

Identifier Source: secondary_id

CDR0000441025

Identifier Type: -

Identifier Source: org_study_id

NCT01731626

Identifier Type: -

Identifier Source: nct_alias