Surgery, Gemcitabine, Cisplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Non-Small Cell Lung Cancer

This study has been terminated.
(Poor accrual)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center Identifier:
First received: September 13, 2007
Last updated: October 7, 2015
Last verified: October 2015

RATIONALE: Drugs used in chemotherapy, such as gemcitabine 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) together with radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well surgery followed by gemcitabine, cisplatin, and radiation therapy works in treating patients with stage II or stage III non-small cell lung cancer.

Condition Intervention Phase
Lung Cancer
Drug: cisplatin
Drug: gemcitabine hydrochloride
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: immunohistochemistry staining method
Procedure: adjuvant therapy
Procedure: conventional surgery
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multimodality Therapy for Stages II and III Non-Small Cell Lung Cancer: Surgical Resection Followed by Sequential Administration of Gemcitabine Plus Cisplatin Chemotherapy and Radiation Therapy

Resource links provided by NLM:

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Two-year Progression-free Survival From the Date of Surgery [ Time Frame: 2 years post-surgery ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier. Progression defined as a 25% increase or an increase of 10 cm2 (whichever is smaller) in the sum of the products of all measurable lesions over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion that had disappeared, or appearance of any new lesion/site, or failure to return for evaluation or death, or deteriorating condition (unless clearly unrelated to this cancer).

Enrollment: 3
Study Start Date: August 1999
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine + Cisplatin
Surgical resection followed by (within 60 days) by chemotherapy (Gemcitabine at 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle and Cisplatin at 75 mg/m2 IV over 1 hour on day 8 of a 21 day cycle) followed by radiation therapy (treated using linear accelerator with photon beam energy of 6-21 MV) upon completion of 3 cycles of chemotherapy.
Drug: cisplatin Drug: gemcitabine hydrochloride Genetic: gene expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: immunohistochemistry staining method Procedure: adjuvant therapy Procedure: conventional surgery Radiation: radiation therapy

Detailed Description:


  • To assess overall survival and progression-free survival of patients with stage II-IIIB non-small cell lung cancer undergoing surgical resection, followed by adjuvant chemotherapy comprising gemcitabine and cisplatin, and radiotherapy.
  • To assess the toxicities of this regimen in these patients.
  • To evaluate the mRNA expression of enzymes (i.e., excision repair cross complementing protein, ribonucleotide reductase, and cytidine/deoxycytidine deaminase and kinase), which may be important in regulating the cytotoxicity of gemcitabine and cisplatin in patient tumors.
  • To correlate mRNA levels with progression-free survival of patients treated with this regimen.
  • To assess BCL2, P53, and HER2-neu expression by IHC and correlation with progression-free survival.

OUTLINE: Patients undergo surgical resection of their tumor and mediastinal lymph node dissection. Patients with complete surgical eradication of their disease or pathologic evidence of microscopic residual disease proceed to adjuvant chemotherapy.

Within approximately 60 days after surgical resection, patients receive adjuvant chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Beginning 130-144 days after surgery, patients undergo radiotherapy once daily, five days a week, for approximately 6 weeks.

Tumor tissue specimens are obtained at the time of surgical resection for pharmacodynamic and biomarker correlative studies. Specimens are examined by reverse transcriptase-polymerase chain reaction to measure mRNA expression of target oncogenes (i.e., DNA repair gene ERCC-1 and M2 subunit of the DNA repair gene ribonucleotide reductase) and enzymes (i.e., cytidine/deoxycytidine deaminase and kinase). Resected specimens are also assessed by IHC for the expression of BCL2, P53, and HER2-neu genes.

After completion of study therapy, patients are followed every 6 months for 5 years and annually thereafter.


Ages Eligible for Study:   18 Years to 120 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed single, primary bronchogenic non-small cell lung cancer meeting the following subtypes:

    • Adenocarcinoma (no bronchioalveolar cell histology)
    • Squamous cell carcinoma
    • Large cell carcinoma
  • Meeting the following staging criteria:

    • Stage IIB (T2, N1, M0, or T3, N0, M0)
    • Stage IIIA (T1-3, N2, M0 or T3, N1, M0)
    • Stage IIIB (Any T, N3, M0 or T4, Any N, M0)
  • No more than 1 parenchymal lesion in the same lung or in both lungs
  • No tumor involving the superior sulcus (e.g., Pancoast tumor)
  • Patients must undergo evaluation by the involved thoracic surgeon, medical oncologist, and radiation oncologist prior to registration
  • No evidence of metastatic disease

    • Biopsy or aspiration cytology required to confirm the benign diagnosis of CT or MRI abnormalities that potentially represent metastatic disease
    • Biopsy required if all noninvasive tests are indeterminant


  • Karnofsky performance status 70-100%
  • Absolute granulocyte count ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Bilirubin ≤ 3 times upper limit of normal (ULN)
  • SGOT and SGPT ≤ 3 times ULN
  • Creatinine clearance > 50 mL/min
  • No prior malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or any other cancer from which the patient has been disease-free for 5 years
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective protection
  • No significant hearing loss or patient unwilling to accept potential for further hearing loss
  • No uncontrolled medical illness by appropriate medical therapy (e.g., myocardial infarction within the past 3 months or liver cirrhosis)
  • No symptomatic peripheral neuropathy affecting activities of daily living


  • No prior chemotherapy or radiotherapy for lung cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00530634

Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Marianna Koczywas, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center Identifier: NCT00530634     History of Changes
Other Study ID Numbers: 99077, P30CA033572, CHNMC-99077, CDR0000564760
Study First Received: September 13, 2007
Results First Received: August 19, 2015
Last Updated: October 7, 2015
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Anti-Infective Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on November 25, 2015