Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer

A Phase I Study of Induction Carboplatin / Paclitaxel Chemotherapy, Pre-operative Radiotherapy With Gadolinium Texaphyrin (Gd-Tex), and Surgical Resection in Stage IIIA (N2) Non-small Cell Lung Carcinoma.

Phase I trial to study the effectiveness of combining carboplatin and paclitaxel, radiation therapy with gadolinium texaphyrin, and surgery in treating patients who have stage IIIA non-small cell lung cancer. Drugs used in chemotherapy use 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. Drugs such as gadolinium texaphyrin may make the tumor cells more sensitive to radiation therapy. Combining chemotherapy, radiation therapy, and surgery may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Stage IIIA Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: paclitaxel; Drug: carboplatin; Radiation: radiation therapy; Drug: motexafin gadolinium; Procedure: conventional surgery

Detailed Description

OBJECTIVES:

I. Determine and compare the frequency and grade of toxicities with the use of gadolinium texaphyrin as a radiosensitizer at two dose levels during preoperative radiotherapy in patients with stage IIIA non-small cell lung cancer.

II. Measure the tumor, involved lymph nodes, and normal lung concentrations of gadolinium and compare to the image pixel intensity obtained by the 1.5 Tesla MRI in this patient population given this regimen.

OUTLINE: This is a dose escalation study of gadolinium texaphyrin (Gd-Tex).

Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.

Cohorts of 3-6 patients receive escalating doses of Gd-Tex until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients are followed at 1 month and then every 4 months for 5 years.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed non-small cell carcinoma of the lung

• Surgical staging with mediastinoscopy or anterior thoracotomy required

  • T1-T3, N2, M0
  • Must appear resectable
• Performance status - Karnofsky 70-100%
• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin normal
• AST no greater than 2.5 times upper limit of normal
• Creatinine no greater than 2 mg/dL
• Creatinine clearance at least 60 mL/min
• No symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• FEV greater than 0.8 L
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Weight loss no greater than 10% of total body weight within past 3 months
• No evidence of neuropathy
• No history of allergy to platinum compounds, paclitaxel, porphyrins, or antiemetics appropriate for administration in conjunction with protocol chemotherapy
• No concurrent uncontrolled illness (e.g., active infection)
• No medical contraindication to MRI (e.g., pacemaker or aneurysm clip)
• No G6PD deficiency
• No known history of porphyria
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
• No prior chest radiotherapy in area of tumor/nodes
• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I; Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 1-2 hours every 3 weeks for 3 courses. Three weeks after completion of induction chemotherapy, patients receive Gd-Tex IV over 30 minutes twice weekly for 10 doses during preoperative radiotherapy. Radiotherapy is administered daily 5 days a week for 5 weeks. Approximately 3.5 weeks after completion of preoperative radiotherapy, patients undergo complete surgical resection. Three hours prior to surgery, patients receive an eleventh dose of Gd-Tex if they do not develop grade 3 or 4 toxicity with the tenth dose. Patients also receive a MRI without contrast prior to surgery. If the tumor is found to be unresectable, patients may receive additional radiation and/or chemotherapy.

Drug: paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; TAX; Drug: carboplatin; Given IV; Other Names: Carboplat; CBDCA; JM-8; Paraplatin; Paraplat; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation; Drug: motexafin gadolinium; Given IV; Other Names: gadolinium texaphyrin; Gd (III) Texaphryin; Gd-Tex; PCI-0120; Xcytrin; Procedure: conventional surgery; Undergo complete surgical resection; Other Names: surgery, conventional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose, defined as that dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) graded according to CTC version 2.0	Up to day 119

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentrations of gadolinium in tumor, tumor involved lymph nodes, normal lung, and blood	Up to day 123
Image pixel intensities in tumor, tumor involved lymph nodes, normal lung, and blood obtained by 1.5 Tesla MRI	Up to day 119

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John Grecula, Ohio State University

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): December 1, 2003

Study Registration Dates

• First Submitted: April 6, 2000
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimate): May 7, 2003

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Photosensitizing Agents; Dermatologic Agents; Carboplatin; Paclitaxel; Motexafin gadolinium
• Other Study ID Numbers: NCI-2012-01401; U01CA076576 (U.S. NIH Grant/Contract); OSU 0003; OSU-0003; NCI-T99-0073; OSU-99H0355; OSU-T99-0073; CDR0000067669