Cetuximab Plus Conformal Thoracic Radiotherapy in Patients (Pts) With Inoperable or Unresectable Locally Advanced Non-Small Cell Lung Cancer (LA - NSCLC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00673738
First received: May 5, 2008
Last updated: March 3, 2014
Last verified: December 2013
  Purpose

This research is being done to find out if a treatment consisting of a combination of thoracic radiotherapy with cetuximab, given together, and followed by chemotherapy with docetaxel and cetuximab (also given together) will kill the cancer cells in the patient's body and shrink the size of their tumor without causing unacceptable side effects. This may allow patients to live longer or decrease the frequency and/or severity of the symptoms caused by the cancer without increasing the frequency and/or severity of the symptoms caused by the treatment.


Condition Intervention Phase
Lung Cancer
Drug: Cetuximab
Radiation: Conformal Thoracic Radiotherapy (CTRT)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy (Phase II) Study of Concurrent Cetuximab Plus Conformal Thoracic Radiotherapy in (Poor Prognosis) Patients With Inoperable or Unresectable, Locally Advanced Non-Small Cell Lung Cancer (LA - NSCLC)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Median Progression Free Survival (PFS) [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Progression Free Survival is defined as the interval between the date of the first cetuximab administration and the date of objective progression of disease. Progression was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.


Secondary Outcome Measures:
  • Median Overall Survival (OS) [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization until death from any cause.

  • Overall Response Rate (ORR) [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    ORR = Complete Response (CR) + Partial Response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response: Disappearance of all target lesions; Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.


Enrollment: 27
Study Start Date: April 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab Plus Radiotherapy
Concurrent Cetuximab plus Conformal Thoracic Radiotherapy (CTRT). Patients were treated with definitive radiotherapy (70 Gy in 35 fractions, per our currently-existing institutional standard) with concurrent cetuximab followed by 3 cycles of consolidation docetaxel plus cetuximab.
Drug: Cetuximab
  • Cetuximab dose: based on patient's actual weight. Loading phase dose of cetuximab is 400 mg/m2 IV administered over 120 minutes, on day 1 followed by; Concurrent phase, weekly infusion dose at 250 mg/m2 IV over 60 minutes, on days 8, 15, 22, 29, 36, 43, 50.
  • Radiation will be accompanied by weekly Cetuximab. Weekly Cetuximab will start on 1st day of radiation (Day 8). So, total number of cetuximab administrations will vary from 7 to 8. Patients will have every other week complete blood counts (CBCs), differentials, and blood urea nitrogen (BUN) plus creatinine and Mg. If patient's ANC drops below 1,000 and/or the platelet count below 75,000 during CTRT, the corresponding, weekly dose of cetuximab will be omitted.
Other Names:
  • Chemotherapy single agent systemic
  • docetaxel
  • immunotherapy
Radiation: Conformal Thoracic Radiotherapy (CTRT)
  • Radiation will be accompanied by weekly Cetuximab. Weekly Cetuximab will start on 1st day of radiation (Day 8). So, total number of cetuximab administrations will vary from 7 to 8. Patients will have every other week CBCs, differentials, and BUN plus creatinine and Mg. If patient's ANC drops below 1,000 and/or the platelet count below 75,000 during CTRT, the corresponding, weekly dose of cetuximab will be omitted.
  • Radiation therapy will begin on day 8 (with window of ± 3 days). Adequate hematologic profile (ANC >1,000 and platelets >75,000) required. Patient may be delayed for a max. of 2 weeks. If > 2 week delay occurs, patient will come off study.
Other Names:
  • CTRT
  • Radiotherapy

Detailed Description:

Patients will be asked to spend about six months in this study. There will be 4 different phases in this study as follows: (1) Loading Phase: This is the first week (week 1) of the study, when patients receive their first (loading) dose of cetuximab only, in the vein. (2) Concurrent Phase: During this phase patients will be treated simultaneously (concurrently) with radiation therapy to their chest and cetuximab. Radiation is delivered 5 days a week, Monday to Friday for a total of 7 weeks (weeks 2-8). Cetuximab is delivered in the vein, weekly, during the weeks of radiation. (3) Recovery Phase: Patients receive no treatment during these next 3 weeks (weeks 9-11). This phase is designed to allow patients to recover from side effects before they start the last phase. (4) Consolidation Phase: The last phase. Patients will receive 3 doses of chemotherapy with docetaxel during this phase. Docetaxel is given intravenously every 21 days. Patients also receive weekly cetuximab during this phase. Cetuximab is delivered in a similar way as it was during the concurrent (second) phase of this study. In total, this phase lasts 6 weeks (weeks 12-18). Once the therapy treatment is completed, and if the patient's cancer did not get worse, follow up visits will include visits to their physician every three months for 2 years, then every 4 months for 2 years or more, as long as their cancer doesn't get worse (at which time they will be removed from the study).

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed inoperable or unresectable, LA-NSCLC (adenocarcinoma, squamous cell carcinoma or anaplastic large cell carcinoma or non-small cell otherwise not specified).
  • Eligible Stages: Stages IIA through IIIA disease if it is felt that they are not candidates for possible resection, medically or otherwise. Stage IIIA (multi-station mediastinal lymph nodes) and stage IIIB disease without significant pleural effusion (metastases to contralateral mediastinal or supraclavicular lymph nodes) are also eligible.
  • Age ≥ 70 OR Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2 at time of registration OR weight loss ≥ 5% in the preceding three months to the time of registration
  • Must have measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. When applicable, baseline measurements/evaluations must be obtained within 4 weeks prior to registration.
  • Must have adequate bone marrow reserve as determined by the following laboratory values, obtained within 14 days prior to registration:

    • White blood cell count (WBC) ≥ 4000/ul or absolute neutrophil count (ANC) ≥ 1000/ul
    • Platelet count ≥ 100,000/ul
    • Hemoglobin ≥ 8 gms/dl
  • Adequate renal and liver function as determined by the following laboratory values, obtained within 14 days prior to registration:

    • Serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥ 40 cc/min
    • Bilirubin < 2.0 mg/dl
    • serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 times the upper limit of normal(ULN)
  • Written, informed consent must be obtained prior to registration
  • Women of childbearing potential (WOCBP) must use an accepted, effective method of contraception during the course of the study, in a manner such that risk of failure is minimized. Sexually active males enrolled should understand the risks to any sexual partner of childbearing potential; must also practice an effective method of contraception. WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy; have a negative pregnancy test within 7 days prior to first receiving investigational product; be instructed to contact the Investigator immediately if they suspect they might be pregnant at any time during study participation. Investigator must immediately notify Bristol-Myers Squibb (BMS) in the event of a confirmed pregnancy in a patient participating in the study. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study.

Exclusion Criteria:

  • Must not have small cell carcinoma as part of the histological specimen
  • Evidence of distant metastasis.
  • History of a prior or concomitant malignancy in the past 3 years except for surgically cured basal cell carcinoma of the skin or carcinoma in situ of the cervix. Invasive malignancies, properly treated and currently disease-free > 3 years are allowed.
  • Prior thoracic radiotherapy or epidermal growth factor receptor (EGFR) pathway targeting therapy. Prior systemic chemotherapy is allowed if received as therapy for an invasive malignancy, currently disease-free > 3 years
  • Concomitant life threatening or uncontrolled serious medical illness such as cardiac disease (uncontrolled hypertension, arrhythmia, unstable angina, recent myocardial infarction, end stage congestive heart failure, cardiomyopathy with decreased ejection fraction), liver disease with significant hepatic insufficiency, kidney disease with significant renal insufficiency or organic brain syndrome.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00673738

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bristol-Myers Squibb
Investigators
Principal Investigator: Alberto Chiappori, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00673738     History of Changes
Other Study ID Numbers: MCC-15294, 106296, CA225286
Study First Received: May 5, 2008
Results First Received: September 18, 2013
Last Updated: March 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Lung
Thoracic
Immunotherapy
Radiotherapy
LA - NSCLC
Non-Small Cell Lung Cancer

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
Docetaxel
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014