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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

Molecular and Genetic Changes in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Cisplatin and Alimta - Phase II Study

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00248495
Enrollment
38
Registered
2005-11-04
Start date
2005-06-08
Completion date
2017-04-05
Last updated
2017-07-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGcisplatin

Given IV

DRUGpemetrexed disodium

Given IV

PROCEDUREadjuvant therapy

Metastasis prevention/control

PROCEDUREconventional surgery

Undergoing tissue removal

PROCEDUREneoadjuvant therapy

Tumor Reduction

Sponsors

Roswell Park Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Pathologically Complete Response1 yearPathologic Complete Response is defined by a surgical pathology specimen, which is free of all gross and microscopic evidence of viable tumor.

Secondary

MeasureTime frameDescription
Number of Participants With Adverse Events1 yearFrequency of Adverse Events, Graded According to NCI CTCAE v3.0. Please refer to the adverse event reporting for more detail.
Overall SurvivalEvery 6 months until the time of death up to 126 monthsOverall survival was defined as time from date of treatment initiation until date of death due to any cause.
Disease Free SurvivalAt 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 monthsProgressive 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 GARFT1 year
Percent Change in SUV Level Between Pre and Post ChemotherapyBaseline and post-chemotherapyPercent change of PET/SUV levels between baseline and post-chemotherapy.

Countries

United States

Participant flow

Participants by arm

ArmCount
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 cisplatin: Given IV pemetrexed disodium: Given IV adjuvant therapy: Metastasis prevention/control conventional surgery: Undergoing tissue removal neoadjuvant therapy: Tumor Reduction
38
Total38

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyWithdrawal by Subject1

Baseline characteristics

CharacteristicNeoadjuvant Chemotherapy
Age, Continuous60.8 years
STANDARD_DEVIATION 9.4
Sex: Female, Male
Female
19 Participants
Sex: Female, Male
Male
19 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
37 / 38
serious
Total, serious adverse events
14 / 38

Outcome results

Primary

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.

Time frame: 1 year

Population: ll treated and eligible patients

ArmMeasureValue (NUMBER)
Neoadjuvant ChemotherapyPathologically Complete Response0 percentage of participants
Secondary

Correlation Between Response and Markers Such as Presence or Absence of ERCC1 and DHFR, TS, DPD and GARFT

Time frame: 1 year

Population: No participants were analyzed as there was no budget left to do the analysis.

Secondary

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.

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

Population: All treated and eligible patients

ArmMeasureValue (MEDIAN)
Neoadjuvant ChemotherapyDisease Free Survival34.5 months
Secondary

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.

Time frame: 1 year

Population: All treated and eligible patients

ArmMeasureCategoryValue (COUNT_OF_PARTICIPANTS)
Neoadjuvant ChemotherapyNumber of Participants With Adverse EventsGrade 12 Participants
Neoadjuvant ChemotherapyNumber of Participants With Adverse EventsGrade 213 Participants
Neoadjuvant ChemotherapyNumber of Participants With Adverse EventsGrade 319 Participants
Neoadjuvant ChemotherapyNumber of Participants With Adverse EventsGrade 44 Participants
Secondary

Overall Survival

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

Population: All treated and eligible patients

ArmMeasureValue (MEDIAN)
Neoadjuvant ChemotherapyOverall Survival100.7 months
Secondary

Percent Change in SUV Level Between Pre and Post Chemotherapy

Percent change of PET/SUV levels between baseline and post-chemotherapy.

Time frame: Baseline and post-chemotherapy

Population: All treated and eligible patients

ArmMeasureValue (MEAN)Dispersion
Neoadjuvant ChemotherapyPercent Change in SUV Level Between Pre and Post Chemotherapy-36.1 Percentage change in SUV levelStandard Deviation 40.6

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026