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

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cisplatin
pemetrexed disodium
adjuvant therapy
conventional surgery
neoadjuvant therapy
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage II non-small cell lung cancer, stage I non-small cell lung cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant chemotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

Pathologically Complete Response
Pathologic Complete Response is defined by a surgical pathology specimen, which is free of all gross and microscopic evidence of viable tumor.

Secondary Outcome Measures

Number of Participants With Adverse Events
Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Please refer to the adverse event reporting for more detail.
Overall Survival
Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Disease Free Survival
Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions. Disease Free Survival was defined as time from date of treatment initiation until date of first documented progression or date of death from any cause, whichever came first.
Correlation Between Response and Markers Such as Presence or Absence of ERCC1 and DHFR, TS, DPD and GARFT
Percent Change in SUV Level Between Pre and Post Chemotherapy
Percent change of PET/SUV levels between baseline and post-chemotherapy.

Full Information

First Posted
November 3, 2005
Last Updated
June 15, 2017
Sponsor
Roswell Park Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT00248495
Brief Title
Pemetrexed Disodium and Cisplatin in Treating Patients Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer
Official Title
Molecular and Genetic Changes in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Cisplatin and Alimta - Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
June 8, 2005 (Actual)
Primary Completion Date
April 29, 2011 (Actual)
Study Completion Date
April 5, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Roswell Park Cancer Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage II non-small cell lung cancer, stage I non-small cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Neoadjuvant chemotherapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Intervention Description
Metastasis prevention/control
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Description
Undergoing tissue removal
Intervention Type
Procedure
Intervention Name(s)
neoadjuvant therapy
Intervention Description
Tumor Reduction
Primary Outcome Measure Information:
Title
Pathologically Complete Response
Description
Pathologic Complete Response is defined by a surgical pathology specimen, which is free of all gross and microscopic evidence of viable tumor.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Please refer to the adverse event reporting for more detail.
Time Frame
1 year
Title
Overall Survival
Description
Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
Time Frame
Every 6 months until the time of death up to 126 months
Title
Disease Free Survival
Description
Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions. Disease Free Survival was defined as time from date of treatment initiation until date of first documented progression or date of death from any cause, whichever came first.
Time Frame
At least every 3 months after the completion of adjuvant therapy for two years and thereafter every 6 months for 3 years and then yearly up to 126 months
Title
Correlation Between Response and Markers Such as Presence or Absence of ERCC1 and DHFR, TS, DPD and GARFT
Time Frame
1 year
Title
Percent Change in SUV Level Between Pre and Post Chemotherapy
Description
Percent change of PET/SUV levels between baseline and post-chemotherapy.
Time Frame
Baseline and post-chemotherapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Grace K. Dy, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States

12. IPD Sharing Statement

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

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