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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00530634
• Other study ID #: 99077
• Secondary ID: P30CA033572CHNMC
• Status: Terminated
• Phase: Phase 2
• First received: September 13, 2007
• Last updated: October 7, 2015
• Start date: August 1999
• Est. completion date: June 2013

Study information

• Verified date: October 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

OBJECTIVES:

• 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for lung cancer

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• cisplatin

• gemcitabine hydrochloride

Genetic:
• gene expression analysis

• reverse transcriptase-polymerase chain reaction

Other:
• immunohistochemistry staining method

Procedure:
• adjuvant therapy

• conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Two-year Progression-free Survival From the Date of Surgery	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).	2 years post-surgery	No