Ph II Concurrent Chemo t/Docetaxel/Carboplatin/Radio Therapy-consolidation t/Locally Adv Inoperable Non-Small Cell Lung Cancer (NSCLC)

PhII Study of Concurrent Chemoradiotherapy With Weekly Docetaxel, Carboplatin and Radiation Therapy Followed by Consolidation Chemotherapy With Docetaxel and Carboplatin for Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC)

RATIONALE: Because of its success in advanced NSCLC both as a single agent and in combination with other chemotherapeutics, it is reasonable to investigate the efficacy and toxicity of docetaxel as a multimodality regimen in this patient population. Docetaxel at a dose of 20 mg/m2 appears to be a well-tolerated "weekly" dose when combined with either cisplatin 25 mg/m2 20-22 or carboplatin area under the curve (AUC) 2 23-25 concomitant with radiation therapy.

PURPOSE: To explore the potential benefits of the radiosensitizing effects of weekly docetaxel/carboplatin/radio therapy concurrent therapy followed full dose systemic docetaxel/carboplatin consolidation therapy on overall response rate, survival, progression-free survival, safety and toxicity in patients with locally advanced NSCLC.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Docetaxel; Radiation: radiation therapy

Detailed Description

OBJECTIVES:

Primary

• To determine the overall survival (0S) for advanced NSCLC patients receiving concurrent chemoradiotherapy with weekly docetaxel, carboplatin and radiation therapy followed by two cycles of consolidation chemotherapy with docetaxel and carboplatin.

Secondary

• To determine the overall response rate in patients treated with this regimen.
• To determine the time to disease progression in patients treated with this regimen.
• To assess the safety and tolerability of this regimen in these patients.

OUTLINE:

• This is a Phase II, open label, multi-center study to determine the overall survival rate for patients treated with concurrent chemoradiotherapy with weekly docetaxel, carboplatin and radiation followed by two cycles of consolidation chemotherapy with docetaxel and carboplatin. Eligible patients will receive concurrent therapy with docetaxel (20 mg/m2) administered weekly for seven weeks as a 30-minute intra-venous (IV) infusion followed by carboplatin (AUC 2) administered weekly for seven weeks as a 30-minute IV infusion. Concurrent radiation therapy will be administered at a dose of 1.8 Gy daily 5 days/week for 25 fractions followed by a dose of 2.0 Gy daily, 5 days/week for 9 fractions (total of 34 fractions). There will be a three-week rest period following the end of the concurrent chemotherapy after which the consolidation phase will begin. During this phase of the study, patients will be treated with docetaxel (75 mg/m2) administered as a 1-hour IV infusion followed by carboplatin (AUC 6) administered as a 30-minute IV infusion. Patient will be treated every three weeks for a total of two cycles.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center, Orlando
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Chesapeake Oncology Hematology Associates
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospital of Cleveland
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital - John & Dorothy Morgan Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Health System
    • Clarksville, Tennessee, United States, 37043
      • Clarksville Regional Hematology Oncology Group
    • Jackson, Tennessee, United States, 38301
      • Jackson Madison County Hospital
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
    • Knoxville, Tennessee, United States, 37920
      • Tennessee Cancer Specialists
    • Memphis, Tennessee, United States, 38120
      • The West Clinic, PC
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Health Services
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

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:

• Patients must voluntarily sign and date an informed consent before the initiation of any study procedures
• Patients must have non-metastatic, inoperable, Stage IIIA or IIIB histologically or cytologically documented NSCLC without evidence of malignant pleural effusion
• Patients must not have received any prior systemic chemotherapy, thoracic radiotherapy or surgical resection for treatment of NSCLC
• Patients must have at least one site of unidirectionally measurable disease
• Patients must be ≥ 3 weeks from a formal exploratory thoracotomy
• Patients must have a Radiation Oncology and Medical Oncology consult and approval prior to study entry
• Patients must be ≥ 18 years of age
• Women of childbearing potential must have a negative baseline serum pregnancy within 7 days prior to Week 1, Day 1 and must not be breast feeding.
• Women of childbearing potential and men with a sexual partner of child bearing potential must use an effective method of contraception beginning prior to study entry, for the duration of the study participation and for a minimum of 3 months after the last dose of chemotherapy.

• Patients must have adequate hepatic, renal, lung and bone marrow function as defined below:

  • Absolute neutrophil count (ANC) > 1,500/mm3
  • Hemoglobin > 9.0 gm/dL
  • Creatinine < 1.5
  • Platelets > 100,000/mm3
  • Total bilirubin within normal limits (WNL)
  • AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility, as per chart on page 10 of the protocol.
• Calculated CrCl > 50 ml/min (via Cockroft-Gault formula).
• Forced expiratory volume in 1 second (FEV 1) > 800 ml

Exclusion Criteria:

• Known hypersensitivity to drugs formulated with polysorbate 80
• Peripheral neuropathy Grade ≥ 2.
• Wet stage IIIB (documented malignant pleural effusion) or stage IV NSCLC
• Previous chemotherapy or radiation therapy
• Any concomitant malignancy, brain metastasis or uncontrolled, clinically significant medical or psychiatric disorder
• Pregnant or nursing women
• A greater than or equal to 10% weight loss over the past 3 months

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: Therapeutic Intervention

Drug: Carboplatin; Carboplatin will be given weekly for seven weeks beginning on Day 1 of the study as a 30-minute intravenous infusion during concurrent therapy. Carboplatin will be given once every three weeks as a 30-minute intravenous infusion immediately following the infusion of docetaxel. Patients will receive two cycles of consolidation treatment.; Other Names: None specified; Drug: Docetaxel; Docetaxel will be given weekly for seven weeks beginning on Day 1 of the study as a 30-minute intravenous infusion during concurrent therapy. Docetaxel will be given once every three weeks administered as a one-hour IV infusion. Patients will receive two cycles of consolidation treatment (1 cycle = 3 weeks).; Other Names: Taxotere; Radiation: radiation therapy; Radiotherapy will be administered daily X 5 day/week for 34 days beginning on Day 1 of the study. Radiotherapy will follow immediately after the infusions of docetaxel and carboplatin.; Other Names: none specified

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Months from on-study to expired/last date known alive.	14.95 months (average duration, on study date to off-study date)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Patient response to treatment per RECIST: Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started Complete response (CR): disappearance of all target lesions Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD	on-study date to date of best response
Time to Disease Progression	Time to disease progression in months	on-study date to date of progression
Number of Participants With Adverse Events by Grade	Number of participants with adverse events, according to grade of event, using the NCI Common Toxicity Criteria (version 2.0) grading system to assign a grade to each event with 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = death related to adverse event	30 days after last treatment.

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Director: Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: April 19, 2008
• First Submitted That Met QC Criteria: April 19, 2008
• First Posted (Estimate): April 22, 2008

Study Record Updates

• Last Update Posted (Estimate): September 7, 2012
• Last Update Submitted That Met QC Criteria: August 30, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer
• 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; Docetaxel; Carboplatin
• Other Study ID Numbers: VICC THO 0319; VU-VICC-THO-0319; VU-VICC-030269