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

• ClinicalTrials.gov Identifier: NCT00664105
• Recruitment Status: Terminated
• First Posted: April 22, 2008
• Results First Posted: March 22, 2011
• Last Update Posted: September 7, 2012
• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Lung Cancer	Drug: Carboplatin; Drug: Docetaxel; Radiation: radiation therapy	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: February 2004
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

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 Name: 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 Name: 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 Name: none specified

Outcome Measures

Primary Outcome Measures :

1. Overall Survival [ Time Frame: 14.95 months (average duration, on study date to off-study date) ]
   Months from on-study to expired/last date known alive.

Secondary Outcome Measures :

1. Overall Response Rate [ Time Frame: on-study date to date of best response ]

   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

2. Time to Disease Progression [ Time Frame: on-study date to date of progression ]
   Time to disease progression in months
3. Number of Participants With Adverse Events by Grade [ Time Frame: 30 days after last treatment. ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Florida

M.D. Anderson Cancer Center, Orlando

Orlando, Florida, United States, 32806

United States, Maryland

Chesapeake Oncology Hematology Associates

Baltimore, Maryland, United States, 21225

United States, Ohio

University Hospital of Cleveland

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Lehigh Valley Hospital - John & Dorothy Morgan Cancer Center

Allentown, Pennsylvania, United States, 18103

United States, Tennessee

Erlanger Health System

Chattanooga, Tennessee, United States, 37403

Clarksville Regional Hematology Oncology Group

Clarksville, Tennessee, United States, 37043

Jackson Madison County Hospital

Jackson, Tennessee, United States, 38301

Tennessee Cancer Specialists

Knoxville, Tennessee, United States, 37920

University of Tennessee Medical Center

Knoxville, Tennessee, United States, 37920

The West Clinic, PC

Memphis, Tennessee, United States, 38120

St. Thomas Health Services

Nashville, Tennessee, United States, 37205

Meharry Medical College

Nashville, Tennessee, United States, 37208

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

UT Southwestern Medical Center

Dallas, Texas, United States, 75390

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Vanderbilt-Ingram Cancer Center

National Cancer Institute (NCI)

Investigators

• Study Director: Vicki Keedy, MD; Vanderbilt-Ingram Cancer Center

More Information

• Responsible Party: Vicki Keedy, MD, Assistant Professor of Medicine; Clinical Director, Sarcoma Program; Assistant Medical Director, Clinical Trials Shared Resource; Medical Oncologist, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT00664105
• Other Study ID Numbers: VICC THO 0319; VU-VICC-THO-0319; VU-VICC-030269
• First Posted: April 22, 2008
• Results First Posted: March 22, 2011
• Last Update Posted: September 7, 2012
• Last Verified: August 2012

Keywords provided by Vicki Keedy, MD, Vanderbilt-Ingram Cancer Center:

stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carboplatin; Docetaxel; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action