Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC - Full Text View

Sponsor:	H. Lee Moffitt Cancer Center and Research Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00226590

Purpose

This is a single institution Phase II study for patients with unresectable Stage IIIA and IIIB non-small cell lung cancer. The treatment started with 2 cycles of gemcitabine and carboplatin followed by concurrent chemotherapy with radiation. The chemoradiation included using paclitaxel and carboplatin with daily thoracic radiation to a total dose of 74 Gy. Response rate was determined following the chemotherapy with gemcitabine and carboplatin and evaluated again after the chemoradiation. Treatment toxicities were also assessed.

Condition	Intervention	Phase
Lung Cancer	Drug: Gemcitabine Drug: Carboplatin Drug: Paclitaxel Procedure: Radiation	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Trial of Induction Gemcitabine and Carboplatin Followed by Paclitaxel and Carboplatin With Concurrent Thoracic Radiation for Patients With Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Paclitaxel Carboplatin Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

Number of Participants Whose Response Allowed Them to Proceed to Chemoradiation [ Time Frame: Ranging from 2 weeks up to 4 years, 9 months ] [ Designated as safety issue: No ]
Response Rates - Complete Response (CR) + Partial Response (PR): We determined the number of participants whose response (both CT and PET assessment) to two cycles of induction chemotherapy with gemcitabine and carboplatin allowed them to proceed to chemoradiation. Response was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

Secondary Outcome Measures:

Progression Free Survival [ Time Frame: Ranging from 2 weeks up to 4 years, 9 months ] [ Designated as safety issue: No ]
To determine median Progression Free Survival rate. Progression-free survival (PFS) is defined as the interval between the date of the first chemotherapy administration and the date of objective progression or death. Progression was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Overall Survival [ Time Frame: Ranging from 2 weeks up to 4 years, 9 months ] [ Designated as safety issue: No ]
To determine median Overall Survival rate
Treatment Completion [ Time Frame: Ranging from 2 weeks up to 4 years, 9 months ] [ Designated as safety issue: Yes ]
The number of participants who completed all treatment on schedule without dose reductions or delays.

Enrollment:	39
Study Start Date:	April 2003
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Combined Therapy In this trial we adopted the approach of using both induction and concurrent chemotherapy together with TRT planned conformally to a tumor dose of 74 Gy.	Drug: Gemcitabine Induction Chemotherapy. Other Name: Gemzar Drug: Carboplatin Induction Chemotherapy. Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy. Other Name: Paraplatin Drug: Paclitaxel Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy. Other Name: Taxol Procedure: Radiation Radiation Therapy will begin on day 57 if there has been adequate hematologic recovery from Induction Chemotherapy. Other Name: Radiation Therapy

Arms

Assigned Interventions

Experimental: Combined Therapy

In this trial we adopted the approach of using both induction and concurrent chemotherapy together with TRT planned conformally to a tumor dose of 74 Gy.

Drug: Gemcitabine

Induction Chemotherapy.

Other Name: Gemzar

Drug: Carboplatin

Induction Chemotherapy. Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy.

Other Name: Paraplatin

Drug: Paclitaxel

Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy.

Other Name: Taxol

Procedure: Radiation

Radiation Therapy will begin on day 57 if there has been adequate hematologic recovery from Induction Chemotherapy.

Other Name: Radiation Therapy

Detailed Description:

In this trial we adopted the approach of using both induction and concurrent chemotherapy together with Thoracic Radiation Therapy (TRT) planned conformally to a tumor dose of 74 Gy. Substitution of gemcitabine for paclitaxel in the induction chemotherapy allowed us to evaluate the impact of RRM1 expression on the activity of this agent. The expression of Ribonucleotide Reductase, M1 Subunit (RRM1) was evaluated prior to initiation of therapy, following induction chemotherapy but prior to concurrent chemoradiation, and following completion of all therapy by CT-guided core needle biopsies. This is a single institution phase II clinical trial, of induction treatment with gemcitabine and carboplatin followed by concurrent chemoradiation using paclitaxel and carboplatin and daily thoracic radiation to a total dose of 74 Gy for patients with unresectable Stage IIIA and IIIB NSCLC. The specific clinical objectives of this study are as follows: To determine the response rate (both CT scan and PET scan assessment) to two cycles of induction chemotherapy with gemcitabine and carboplatin; To determine the response rate (both CT scan and PET scan assessment) to concurrent thoracic radiation and weekly paclitaxel and carboplatin; To evaluate the patterns of local and distant failure for patients treated with induction chemotherapy followed by concurrent chemoradiation according to this regimen; To estimate the median, 1 year, and overall survival; To assess acute and long term toxicities of treatment.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Eligibility Criteria:

Histologically confirmed unresectable non-small cell carcinoma of the lung (adenocarcinoma, squamous cell carcinoma or anaplastic large cell carcinoma). See below for TNM eligibility. Mediastinoscopy or thoracoscopy in patients with mediastinal lymph node enlargement of < 2 cm on CT scans of suspicious on PET scan to confirm suspected involvement. These staging procedures are not mandatory for patients with obvious nodal involvement (2.0 cm or greater). Staging system: The New International Staging System for lung cancer (Clifton F. Mountain, 1997) will be followed. The following stages will be eligible:
Patients with stage IIIa disease will be eligible if it is felt that they are not candidates for possible resection following neo-adjuvant therapy (unresectable T3N1 or T1-3 primary tumors with metastasis limited to single station ipsilateral mediastinal lymph nodes). Patients with stage IIIb disease without significant* pleural effusion will be eligible. This includes patients with metastases to contralateral mediastinal or supraclavicular nodes.
Patients without significant pleural effusion will constitute those in whom 1) it is seen on CT scan only or 2) does not reaccumulate after one thoracentesis and is cytologically negative.
No evidence of distant metastasis.
Patients must have measurable disease by the Recist Evaluation Criteria in Solid Tumors (RECIST) criteria. Baseline measurements/evaluations must be obtained within 4 weeks prior to registration.
Patients must not have small cell carcinoma as part of the histological specimen (World Health Organization [WHO] classification 22.40)
Performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 at time of registration.
Patients with preexisting clinically significant peripheral neuropathy are ineligible.
Weight loss of ≤ 5% in the preceding three months
No prior systemic chemotherapy or thoracic radiotherapy.
Patients must have adequate bone marrow reserve as determined by the following laboratory values: Obtained within 14 days prior to registration.
White blood cell count 4000/ul or greater and granulocyte count of 1500/ul or greater
Platelet count of 100,000/ul or greater
Hemoglobin of 10 gms/dl or greater.
Adequate renal and liver function as determined by the following laboratory values: Obtained within 14 days prior to registration.
Serum creatinine < 1.5 mg/dl or creatinine clearance greater than 50 cc/min
Bilirubin less than 1.5 mg/dl
SGOT less than 1.5 times normal
No history of a prior or concomitant malignancy in the past five years except for surgically cured basal cell carcinoma of the skin or carcinoma in situ of the cervix.
No concomitant life threatening or uncontrolled serious medical illness such as cardiac arrhythmia, end stage congestive heart failure, liver disease with significant hepatic insufficiency, organic brain syndrome.
Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.
Age greater than or equal to 18 years
Written, informed consent must be obtained prior to registration.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00226590

Locations

United States, Florida
H. Lee Moffitt Cancer Center & Research Insitute
Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Gerold Bepler, MD, PhD

Karmanos Cancer Institute (formerly at H. Lee Moffitt Cancer Center & Research Institute)

More Information

Additional Information:

Moffiitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gerald Bepler, M.D., Ph.D., Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00226590 History of Changes
Other Study ID Numbers:	MCC-13240, 13189
Study First Received:	September 23, 2005
Results First Received:	March 11, 2011
Last Updated:	May 23, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

non-small cell lung cancer
carcinoma
unresectable

Stage IIIA
Stage IIIB
thoracic radiation

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Carboplatin
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 09, 2012