Phase I Trial of Sorafenib With Concurrent Thoracic Radiotherapy for Poor Prognosis Non-Small Cell Lung Cancer (NSCLC)
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Maximal tolerated dose (MTD) of sorafenib concurrent with thoracic radiation for poor prognosis NSCLC (phase I)
Study Overview
Brief Summary
The goal of this clinical research study is to find the highest safe dose of sorafenib that can be given in combination with radiation therapy to people with lung cancer. The ability of both the study drug and radiation to control the disease will also be studied.
Detailed 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 Dose Escalation:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you joined this study. Up to 4 groups of 3-6 participants will be enrolled in the Phase I portion of the study.
Enrolled in the Phase I portion, the dose of sorafenib you receive will depend on when you joined this study. The first group of participants will receive the lowest dose level of sorafenib. Each new group will receive a higher dose of sorafenib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of sorafenib is found.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •Patients for whom palliative thoracic irradiation therapy to 45 Gy/15 FX is the recommended treatment by their treating radiation oncologist.
- •The primary tumor and/or regional lymphatic metastases must be evaluable radiographically.
- •Age >/= 18 years or older.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 or greater, weight loss </= 30% or less.
- •No prior radiation to the thorax.
- •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
- •Patients with distant metastasis are eligible.
- •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- •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.
- •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.
- •INR < 1.5 or a PT/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.
- •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. The only approved consent form is attached to this protocol.
Exclusion Criteria
- •Cardiac disease: Congestive heart failure > class II 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.
- •Known hemorrhagic brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude hemorrhagic brain metastasis.
- •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- •Uncontrolled hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- •Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- •Active clinically serious infection > CTCAE Grade
- •Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
- •Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
- •Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
- •Serious non-healing wound, ulcer, or bone fracture.
- •Evidence or history of bleeding diathesis or coagulopathy
- •Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
- •Current use of St. John's Wort or rifampin (rifampicin).
- •Known or suspected allergy to sorafenib.
- •Any malabsorption problem.
- •Patients with squamous cell carcinoma.
Arms & Interventions
Sorafenib + Radiation Therapy
Sorafenib starting dose 200 mg orally daily + 45 Gy total in 15 radiation treatments: 3 Gy per day, 5 days a week for 3 weeks
Intervention: Sorafenib (Drug)
Sorafenib + Radiation Therapy
Sorafenib starting dose 200 mg orally daily + 45 Gy total in 15 radiation treatments: 3 Gy per day, 5 days a week for 3 weeks
Intervention: Radiation Therapy (Procedure)
Outcomes
Primary Outcomes
Maximal tolerated dose (MTD) of sorafenib concurrent with thoracic radiation for poor prognosis NSCLC (phase I)
Time Frame: Continual reassessment of safety throughout study and determination of dose-limiting toxicities during and at end of 3 week cycles.
Secondary Outcomes
- Efficacy of combination assessed by tumor response and local progression failure (phase II)(6 Months and 12 Months)