Sorafenib and Thoracic Radiation for Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Phase II Trial of Sorafenib With Concurrent Thoracic Radiotherapy for Poor Prognosis Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01636921
• Other study ID #: 2007-0352 Phase II
• Status: Withdrawn
• Phase: Phase 2
• First received: July 5, 2012
• Last updated: July 9, 2012
• Start date: January 2008
• Est. completion date: January 2011

Study information

• Verified date: July 2012
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The Phase II goal of this clinical research study is to find the efficacy of this combination assessed by tumor response and local progression failure.

Description:

The Study Drug:

Sorafenib is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the growth and behavior of cancer cells.

Study Drug:

Up to 4 groups of 3-6 participants were to be enrolled in the Phase I portion of the study, and up to 30 participants enrolled in Phase II. Phase II participants will receive sorafenib at the highest dose tolerated in the Phase I portion.

All participants will receive the same type and amount of radiation.

Study Drug Administration:

Participants will take sorafenib capsules 1-2 times every day beginning on Day 1 of radiation therapy. Participants will take the study drug 2 times a day. Participants will take the study drug without food (1 hour before or 2 hours after eating).

Radiation Therapy:

Before receiving radiation therapy, the participant will have a "marking session". At this visit, the participant will have a computed tomography (CT) scan that will be used to help to plan out the radiation therapy. This will take about 45 minutes.

Before receiving radiation, the participant will also have a single photon computed tomography (SPECT) scan of your lungs.

The participant will be given 15 radiation treatments, once a day, 5 days a week, Monday-Friday. Each treatment will take about 30 minutes. He or she will sign a separate consent form for radiation therapy and the procedure will be described in more detail.

Clinical Visits:

Participant will have routine clinical visits every week while receiving radiation therapy. The information collected during these clinical visit will be used for the study. At these visits, the following tests and procedures will be performed:

• Participant will have a physical exam, including measurement of your blood pressure and weight.

• Participant will be asked about any side effects you may be experiencing and any new drugs you may be taking.

• Participant will be asked how well you are able to perform the normal activities of daily living (performance status evaluation)

• Blood (about 3-4 teaspoons) will be drawn for routine tests.

• Participant will have any tests that doctor feels medically necessary

Urine will be collected every week while taking sorafenib and receiving radiation therapy for routine tests.

End-of-Study Visit:

Participant will have an end-of-study visit 4-6 weeks after Participant stops receiving radiation. At this visit, Participant will have a CT scan to check the status of the disease.

Follow-Up Visits:

Participant's first follow-up visit will be at 6 weeks (+/- 7 days) after radiation therapy and the second follow-up appointment will be at 10 weeks (+/- 7 days) after radiation therapy. Participant will then have follow up visits every 3 months. At these visits, Participant will go though the following:

• A complete medical history will be recorded.

• Participant will have a physical exam, including measurement of your weight and blood pressure.

• Participant will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).

• Participant will be asked about any drugs you may be taking.

• Blood (about 3-4 teaspoons) and urine will be collected for routine tests.

• Participant will also have chest x-ray.

• Participant will have a computed tomography (CT) scan of your chest area.

• The location, type, and size of all measurable lesions will be recorded.

• If your doctor thinks it is necessary, Participant will have a positron emission tomography(PET)/CT scan.

• If doctor thinks it is necessary, Participant will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart).

• Participant may have a lung perfusion scan to see if all regions of your lung are equally functional or not. This is called lung SPECT scan.

• Participant will have a lung functional test (PFT) if your doctor thinks it is necessary.

All these tests are routine examinations as he/she would have without participating in this study in order to know the status of the disease.

This is an investigational study. Sorafenib is FDA approved and commercially available for renal cell carcinoma. The radiation therapy schedule used for this study is standard treatment for lung cancer patients. The use of sorafenib with radiation therapy is investigational.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Pathologically proven previously untreated or systemically treated poor prognosis NSCLC patients for whom palliative thoracic irradiation is the treatment of choice per standard of care.

2. Patients for whom palliative thoracic irradiation therapy to 45 Gy/15 FX is the recommended treatment by their treating radiation oncologist.

3. The primary tumor and/or regional lymphatic metastases must be evaluable radiographically.

4. Age >/= 18 years or older.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or greater, weight loss </= 30% or less.

6. No prior radiation to the thorax.

7. Adequate bone marrow, liver and renal function as assessed by the following: * Hemoglobin >/= 9.0 g/dl * Absolute neutrophil count (ANC) >/=1,000/mm^3 *Platelet count >/ =100,000/mm^3 * Total bilirubin </= 1.5 times ULN or greater * ALT and AST </= 2.5 times the ULN (</= 5 * ULN for patients with liver involvement) * Creatinine </= 1.5 * ULN

8. Patients with distant metastasis are eligible.

9. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment

10. Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.

11. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

12. International Normalized Ratio (INR) < 1.5 or a Prothrombin time (PT)/Partial Prothrombin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

13. Patients must sign an informed consent indicating that they are aware of the investigational nature of the study in keeping with the policy of M.D. Anderson Cancer Center.

Exclusion Criteria:

1. Cardiac disease: Congestive heart failure > class II New York Hearth Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.

2. Known hemorrhagic brain metastasis. Patients with neurological symptoms must undergo a Computed Tomography (CT) scan/Magnetic Resonance Imaging (MRI) of the brain to exclude hemorrhagic brain metastasis.

3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

4. Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.

5. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

6. Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 3.

7. Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

8. Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.

9. Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.

10. Serious non-healing wound, ulcer, or bone fracture.

11. Evidence or history of bleeding diathesis or coagulopathy

12. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.

13. Current use of St. John's Wort or rifampin (rifampicin).

14. Known or suspected allergy to sorafenib.

15. Any malabsorption problem.

16. Patients with squamous cell carcinoma.

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:
• Sorafenib
200 mg orally twice daily (Maximum Tolerated Dose from Phase I of study) until disease progression.

Procedure:
• Radiation Therapy
45 Gy total in 15 radiation treatments: 3 Gy per day, 5 days a week for 3 weeks

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Bayer

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Complete or Partial Response at 6 Months	Efficacy of combination assessed by tumor response where tumor response is defined as > 60% complete or partial response rate at 6 months. Evaluation of target lesions where Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.	Baseline to 6 Months	No

External Links

•   The University of Texas M.D.Anderson Cancer Center