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

NCT00673738 | Completed Phase 2 Results DMC

• 3 other identifiers: MCC-15294106296CA225286
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lung Cancer

Keywords

Lung; Thoracic; Immunotherapy; Radiotherapy; LA - NSCLC; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Median Progression Free Survival (PFS)

  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.

  Up to 36 months

Secondary Outcomes (2)

• Median Overall Survival (OS)

  Up to 36 months

• Overall Response Rate (ORR)

  Up to 36 months

Study Arms (1)

Cetuximab Plus Radiotherapy

EXPERIMENTAL

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; Radiation: Conformal Thoracic Radiotherapy (CTRT)

Interventions

Cetuximab DRUG

* 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.

Also known as: Chemotherapy single agent systemic, docetaxel, immunotherapy

Cetuximab Plus Radiotherapy

Conformal Thoracic Radiotherapy (CTRT) RADIATION

* 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.

Also known as: CTRT, Radiotherapy

Cetuximab Plus Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Cetuximab; Docetaxel; Immunotherapy; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Immunomodulation; Biological Therapy; Therapeutics

Limitations and Caveats

Accrual, and therefore treatment ended earlier than planned due to pulmonary toxicity. Three participants remain on follow-up.

Results Point of Contact

• Title: Alberto Chiappori, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

alberto.chiappori@moffitt.org

813-745-3050

Study Officials

• Alberto Chiappori, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: May 7, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2013
• Study Completion: August 1, 2015
• Last Updated: October 8, 2015
• Results First Posted: March 4, 2014

Record last verified: 2015-09

Locations

US (1)