Clinical trial NCT00096226: Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage III Non-Small Cell Lung Cancer
Official title: A Phase II Trial Of Neoadjuvant Therapy With Concurrent Chemotherapy And High Dose Radiotherapy Followed By Surgical Resection And Consolidative Therapy For Locally Advanced Non-Small Cell Lung Carcinoma
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: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-11-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
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 paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving paclitaxel and carboplatin together with radiation therapy before surgery may shrink the tumor so that it can be removed. Giving chemotherapy after surgery may kill any tumor cells remaining after surgery.

PURPOSE: This phase II trial is studying how well giving paclitaxel and carboplatin together with radiation therapy works in treating patients who are undergoing surgery for stage III non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Determine the mediastinal node clearance rate in patients with stage IIIA or IIIB non-small cell lung cancer treated with neoadjuvant induction chemoradiotherapy comprising paclitaxel, carboplatin, and high-dose radiotherapy followed by surgical resection for patients found to be resectable and consolidative chemotherapy comprising paclitaxel and carboplatin.
* Determine the rate of complete pathological response in patients treated with this regimen.
* Determine the feasibility of surgical resection after neoadjuvant induction chemoradiotherapy in these patients.
* Determine disease-free and overall survival of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.

Eligibility criteria: Inclusion Criteria:

1. Patients with Stage IIIA (T1-3 N2) or Stage IIIB (N3, excluding supraclavicular involvement) non-small cell lung cancer documented by biopsy or cytology (Pancoast tumors are eligible if pathologic evidence of mediastinal nodal disease is present);
2. Disease must be measurable;
3. Mediastinal lymph nodes must be proven positive by pathologic review. All patients must undergo mediastinoscopy, thoracoscopy, Chamberlain procedure, or transbronchial needle aspirate to evaluate extent of nodal involvement. Any lymph node assessed by mediastinoscopy and found to be positive will be defined as N2 disease;
4. Patients ≥ 18 years of age;
5. Life expectancy ≥ 6 months;
6. Zubrod performance status 0- 1 (See Appendix II);
7. Pretreatment laboratory values must be as follows: White blood cell count (WBC) count: ≥ 3,000/mm\^3; Absolute granulocyte count: ≥ 1,500/mm\^3; Platelets: ≥ 100,000/mm3; Total bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN); Serum creatinine: ≤ 1.5 x institutional ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x institutional ULN; serum albumin: ≥ 3.0 g/dL
8. Baseline forced expiratory volume (FEV1) must be at least 2.0 liters; if less than 2.0 then V/Q scan is required and projected post-operative FEV1 must be \> 800 cc based on the following formula using the quantitative Ventilation/perfusion (V/Q) scan: FEV1 = FEV1 x % perfusion to uninvolved lung from quantitative lung V/Q scan report.
9. Patient evaluation and acceptance by thoracic surgery, medical oncology, and radiation oncology; patient must be a potential surgical candidate prior to the initiation of therapy;
10. Women of childbearing potential and male participants must practice an effective method of contraception during the study;
11. Pretreatment evaluations required for eligibility include:

    * A complete medical history \& physical examination to include Zubrod performance status, neurologic assessment, recent weight loss, usual weight, concurrent non-malignant disease and therapy;
    * Location, type, and size of measurable lesion must be recorded prior to treatment;
    * Complete blood count (CBC) with differential, platelet count, electrolytes, and Mg++ within 14 days prior to study entry;
    * Twelve-channel serum multiple analysis (SMA-12): Total protein, Albumin, Calcium, Glucose, Blood urea nitrogen (BUN), Creatinine, Alkaline Phosphatase, Lactate dehydrogenase (LDH), Total Bilirubin, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) within 14 days prior to study entry;
    * Women of childbearing potential must have a negative pre-study serum or urine pregnancy test within 14 days prior to study entry.
    * Mediastinoscopy, thoracoscopy, Chamberlain procedure, or bronchoscopy with transbronchial needle aspirate to evaluate the extent of lymph node involvement;
    * Computed tomography (CT) scan of the chest to include liver, and adrenal glands within 6 weeks prior to study entry;
    * Positron emission tomography (PET) scan within 8 weeks prior to study entry. Any suspicious areas outside of the local regional disease requires documented evaluation of these findings to exclude metastatic disease;
    * CT scan or magnetic resonance imaging (MRI) of the brain within 6 weeks prior to study entry;
    * Electrocardiogram (EKG) and pulmonary function tests including forced vital capacity (FVC), FEV-1, and diffusing capacity of carbon monoxide (DLCO), within 8 weeks prior to study entry; V/Q scan, if applicable, within 8 weeks prior to study entry.
12. Patients must sign a study-specific informed consent prior to study entry.

Exclusion Criteria:

1. Small cell lung cancer; distant metastatic disease;
2. Evidence of clinical or radiographic supraclavicular lymph node involvement;
3. Bronchioalveolar carcinoma with lobar or multilobar involvement;
4. Unintentional weight loss \> 5% within 6 months prior to study entry, or Zubrod performance status 2 or greater;
5. Primary tumor location prevents delivery of 60 Gy and simultaneously limiting spinal cord dose to 48 Gy;
6. Patients with malignant pleural effusion;
7. Clinically evident superior vena cava syndrome;
8. Prior systemic chemotherapy or radiation therapy to the thorax;
9. Patients with known hypersensitivity to Cremophor EL;
10. Patients receiving other investigational therapy;
11. Pregnant or lactating women are ineligible, as treatment involves unforeseeable risks to the participant and to the embryo or fetus;
12. Patients with an active serious infection or other serious underlying medical condition that would impair their ability to complete protocol treatment;
13. Dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent.

Primary outcomes:
measure: Mediastinal Nodal Clearance Rate
timeFrame: At completion of concurrent chemotherapy and radiation therapy, up to 14 weeks.
Secondary outcomes:
measure: Percentage of Patients With Complete Pathological Response After Concurrent Chemotherapy and Radiation Therapy
timeFrame: At time of surgery (16-18 weeks)
measure: Percentage of Patients With Major Surgical Morbidities Within 30 Days of Surgery
timeFrame: From 0 to 30 days following surgery (surgery occurs within 16-18 weeks after registration)
measure: Percentage of Patients Able to Undergo Surgical Resection
timeFrame: At time of surgery (16-18 weeks)
measure: Distribution of R0, R1, and R2 Resections After Chemotherapy
timeFrame: At time of surgery (16-18 weeks)
measure: Overall Survival at Two Years
timeFrame: From registration to two years
measure: Progression-free Survival at Two Years
timeFrame: From registration to two years
measure: Distribution of Highest Grade Adverse Event
timeFrame: From start of treatment to end of follow-up, a maximum of 64.3 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
state: Arizona
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Camden
country: United States
facility: Cancer Institute of New Jersey at Cooper University Hospital - Camden
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center at ECU Medical School
state: North Carolina
city: Bethlehem
country: United States
facility: St. Luke's Cancer Network at St. Luke's Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Wheeling
country: United States
facility: Schiffler Cancer Center at Wheeling Hospital
state: West Virginia
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
Study officials:
affiliation: University of Maryland Greenebaum Cancer Center
name: Mohan Suntharalingam, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Suntharalingam M, Paulus R, Edelman MJ, Krasna M, Burrows W, Gore E, Wilson LD, Choy H. Radiation therapy oncology group protocol 02-29: a phase II trial of neoadjuvant therapy with concurrent chemotherapy and full-dose radiation therapy followed by surgical resection and consolidative therapy for locally advanced non-small cell carcinoma of the lung. Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):456-63. doi: 10.1016/j.ijrobp.2011.11.069. Epub 2012 Apr 28.
citation: Suntharalingam M, Paulus R, Edelman MJ, et al.: RTOG 0229: A phase II trial of neoadjuvant therapy with concurrent chemotherapy and high-dose radiotherapy (XRT) followed by resection and consolidative therapy for LA-NSCLC. [Abstract] J Clin Oncol 28 (Suppl 15): A-7024, 2010.