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

• ClinicalTrials.gov Identifier: NCT00248495
• Recruitment Status: Completed
• First Posted: November 4, 2005
• Results First Posted: May 19, 2017
• Last Update Posted: July 12, 2017
• Sponsor: Roswell Park Cancer Institute
• Information provided by (Responsible Party): Roswell Park Cancer Institute

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: cisplatin; Drug: pemetrexed disodium; Procedure: adjuvant therapy; Procedure: conventional surgery; Procedure: neoadjuvant therapy	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 8, 2005
• Actual Primary Completion Date: April 29, 2011
• Actual Study Completion Date: April 5, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	Drug: cisplatin; Given IV; Drug: pemetrexed disodium; Given IV; Procedure: adjuvant therapy; Metastasis prevention/control; Procedure: conventional surgery; Undergoing tissue removal; Procedure: neoadjuvant therapy; Tumor Reduction

Outcome Measures

Primary Outcome Measures :

1. Pathologically Complete Response [ Time Frame: 1 year ]
   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 :

1. Number of Participants With Adverse Events [ Time Frame: 1 year ]
   Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Please refer to the adverse event reporting for more detail.
2. Overall Survival [ Time Frame: Every 6 months until the time of death up to 126 months ]
   Overall survival was defined as time from date of treatment initiation until date of death due to any cause.
3. Disease Free Survival [ 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 ]
   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.
4. Correlation Between Response and Markers Such as Presence or Absence of ERCC1 and DHFR, TS, DPD and GARFT [ Time Frame: 1 year ]
5. Percent Change in SUV Level Between Pre and Post Chemotherapy [ Time Frame: Baseline and post-chemotherapy ]
   Percent change of PET/SUV levels between baseline and post-chemotherapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263-0001

Sponsors and Collaborators

Roswell Park Cancer Institute

Investigators

• Principal Investigator: Grace K. Dy, MD; Roswell Park Cancer Institute

More Information

• Responsible Party: Roswell Park Cancer Institute
• ClinicalTrials.gov Identifier: NCT00248495
• Obsolete Identifiers: NCT01731626
• Other Study ID Numbers: CDR0000441025; RPCI I-31104
• First Posted: November 4, 2005
• Results First Posted: May 19, 2017
• Last Update Posted: July 12, 2017
• Last Verified: June 2017

Keywords provided by Roswell Park Cancer Institute:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors