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.
18 Years
N/A
Both
Stage IIIA Non-small Cell Lung Cancer
Trial Information
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.
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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
Outcome Time Frame:
Up to day 119
Safety Issue:
Yes
Principal Investigator
John Grecula
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01401
NCT ID:
NCT00005065
Start Date:
January 2000
Completion Date:
Related Keywords:
- Stage IIIA Non-Small Cell Lung Cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | Columbus, Ohio 43210-1240 |
