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Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Carboplatin
Paclitaxel
Radiation
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring non-small cell lung cancer, carcinoma, unresectable, Stage IIIA, Stage IIIB, thoracic radiation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • H. Lee Moffitt Cancer Center & Research Insitute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combined Therapy

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of Participants Whose Response Allowed Them to Proceed to Chemoradiation
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
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
To determine median Overall Survival rate
Treatment Completion
The number of participants who completed all treatment on schedule without dose reductions or delays.

Full Information

First Posted
September 23, 2005
Last Updated
February 20, 2017
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00226590
Brief Title
Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
April 2003 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
non-small cell lung cancer, carcinoma, unresectable, Stage IIIA, Stage IIIB, thoracic radiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combined Therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Induction Chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin
Intervention Description
Induction Chemotherapy. Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
Weekly Carboplatin and Paclitaxel During Thoracic Radiation Therapy.
Intervention Type
Procedure
Intervention Name(s)
Radiation
Other Intervention Name(s)
Radiation Therapy
Intervention Description
Radiation Therapy will begin on day 57 if there has been adequate hematologic recovery from Induction Chemotherapy.
Primary Outcome Measure Information:
Title
Number of Participants Whose Response Allowed Them to Proceed to Chemoradiation
Description
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.
Time Frame
Ranging from 2 weeks up to 4 years, 9 months
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
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.
Time Frame
Ranging from 2 weeks up to 4 years, 9 months
Title
Overall Survival
Description
To determine median Overall Survival rate
Time Frame
Ranging from 2 weeks up to 4 years, 9 months
Title
Treatment Completion
Description
The number of participants who completed all treatment on schedule without dose reductions or delays.
Time Frame
Ranging from 2 weeks up to 4 years, 9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerold Bepler, MD, PhD
Organizational Affiliation
Karmanos Cancer Institute (formerly at H. Lee Moffitt Cancer Center & Research Institute)
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center & Research Insitute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Induction Gemcitabine & Carboplatin Followed by Paclitaxel & Carboplatin +XRT in NSCLC

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