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

Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00673738
• Other study ID #: MCC-15294
• Secondary ID: 106296CA225286
• Status: Completed
• Phase: Phase 2
• First received: May 5, 2008
• Last updated: September 23, 2015
• Start date: April 2008
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 2015
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

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.

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.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Median Overall Survival (OS)	Overall survival is defined as the time from randomization until death from any cause.	Up to 36 months	No
Secondary	Overall Response Rate (ORR)	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.	Up to 36 months	No

External Links

•   Moffitt Cancer Center Clinical Trials website