Clinical trial NCT00301808: Cisplatin, Pemetrexed Disodium, and Radiation Therapy Followed by Docetaxel in Treating Patients With Stage III Non-Small Cell Lung Cancer
Official title: Phase II Study of Concurrent Cisplatin/Pemetrexed and RT Followed by Docetaxel in Stage III NSCLC (Non Small Cell Lung Cancer)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-03-13
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as cisplatin, pemetrexed disodium, and docetaxel, 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 more than one chemotherapy drug (combination chemotherapy) together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin and pemetrexed disodium together with radiation therapy followed by docetaxel works in treating patients with stage III non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Assess 1-year survival of stage III non-small cell lung cancer (NSCLC) patients treated with cisplatin, pemetrexed disodium, and concurrent thoracic radiotherapy followed by consolidation therapy with docetaxel.

Secondary

* Assess the progression-free survival and overall survival.
* Assess the toxicity of this regimen.

OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over 60 minute on day 1. Treatment repeats every 21 days for 3 courses in the absence of unacceptable toxicity. Patients also receive concurrent thoracic radiotherapy in weeks 1-7. Between 3-8 weeks after completion of chemoradiotherapy, patients with no progressive disease receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for 3 courses.

After completion of study therapy, patients are followed at 1 month and periodically thereafter.

PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria:

  * Stage IIIA disease, meeting all of the following criteria:

    * Mediastinal lymph node involvement

      * Greater than one mediastinal lymph node enlarged on CT scan, confirmed by positron emission tomography (PET) scan
    * Paralyzed left vocal cord with separate lung primary distinct from the aorto-pulmonary lymph nodes on the CT scan
  * Stage IIIB disease, meeting all of the following criteria:

    * N3 lymph node involvement

      * Enlarged N3 lymph nodes on CT scan confirmed by PET scan

        * Lymph node involvement may not extend to cervical lymph nodes other than supraclavicular lymph nodes
    * Right-sided primary tumor with left vocal cord paralysis
    * Evidence of tumor extension into the mediastinum and/or mediastinal structures by mediastinoscopy, bronchoscopy, or CT scan
    * No evidence of malignant pleural effusion unless effusion is only evident on CT scan
    * No more than 1 parenchymal lesions on the same or opposite sides of the lung
* No brain metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

* SWOG performance status 0 or 1
* Platelet count ≥ 100,000/mm³
* Absolute neutrophil count ≥ 1,500/mm³
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* Creatinine clearance ≥ 45 mL/min
* Bilirubin normal
* Transaminases (SGOT and/or SGPT) ≤ 1.5 times ULN
* Alkaline phosphatase ≤ 2.5 times ULN
* Total lung volume (i.e., right and left lung minus the gross tumor volume) receiving greater than 20 Gy of radiation ≤ 40%
* FEV_1 ≥ 70% of predicted
* DLCO ≥ 50 mL/min
* No other concurrent malignancy

  * Prior malignancy allowed provided it is in clinical control and is not likely to impact clinical outcome in the opinion of the treating physician
* No peripheral neuropathy ≥ grade 2
* No serious medical illness, including, but not limited to, any of the following:

  * Uncontrolled congestive heart failure
  * Uncontrolled angina
  * Myocardial infarction
  * Cerebrovascular event within the past 6 months
  * History of chronic active hepatitis
  * History of HIV infection
  * Active bacterial infection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Must be willing and able to take folic acid, cyanocobalamin (vitamin B12), or dexamethasone

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy or radiotherapy for NSCLC
* No concurrent participation in another therapeutic investigational study
* Concurrent ibuprofen (400 mg four times daily) allowed during pemetrexed disodium administration provided the patient has normal renal function
* No concurrent aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) 2 days before, during, and for 2 days after pemetrexed disodium administration

  * Patients on long-acting NSAIDs (e.g. naproxen sodium, diflunisal, nabumetone, or celecoxib) must be willing or able to discontinue usage 5 days prior to, during, and for 2 days after pemetrexed disodium administration

Primary outcomes:
measure: Probability of Overall Survival at One Year
timeFrame: at 1 year
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Approximately 3 weeks after the last cycle of cisplatin/pemetrexed or completion of radiation whichever is the later.
measure: Overall Survival
timeFrame: Date of registration to the date of death
measure: Safety Outcomes
timeFrame: 72 hours after 2nd and 3rd cycles: 30 days after completion of study treatment; Every 2 months thereafter; then once a year
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Veterans Affairs Medical Center - Detroit
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Shirish M. Gadgeel, MD
role: STUDY_CHAIR
References:
citation: Gadgeel SM, Ruckdeschel JC, Patel BB, Wozniak A, Konski A, Valdivieso M, Hackstock D, Chen W, Belzer K, Burger AM, Marquette L, Turrisi A. Phase II study of pemetrexed and cisplatin, with chest radiotherapy followed by docetaxel in patients with stage III non-small cell lung cancer. J Thorac Oncol. 2011 May;6(5):927-33. doi: 10.1097/JTO.0b013e3182156109.