Official Title: “Anti-Angiogenic Chemotherapy: A Phase II Trial of Thalidomide, Celecoxib, Etoposide and Cyclophosphamide in Patients With Relapsed or Progressive Cancer”

This study will use a combination of four oral drugs (thalidomide, cyclophosphamide, etoposide and celecoxib) to treat patients with relapsed or progressive cancer. These drugs are expected to target the blood vessels that supply the tumors with what they need to grow.

Study Type: Interventional

Study Design: Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

- Thalidomide will be given orally every evening and the daily dose will escalate until the patient reaches a dose on which they are comfortable and will given continuously for one year. - Celecoxib will be given orally twice a day and escalated as tolerated for one year. - Etoposide will be given orally once a day for 21 consecutive days. This medication will alternate with oral cyclophosphamide and will continue for one year. - Cyclophosphamide will be given orally once a day for 21 consecutive days and as stated above will alternate with etoposide for one year. - During the treatment, blood tests will be performed every three weeks except during the first 3 week cycle in which testing is performed every 2 weeks. Appropriate imaging studies will be performed every 9 weeks. - The duration of treatment is one year unless the side effects are too harmful or the tumor grows. Treatment may be continued past one year if the drugs are well tolerated and disease progression has not occured.

Primary:

• To evaluate the feasibility of administering thalidomide, celecoxib, etoposide and cyclophosphamide for recurrent and poor prognosis tumors. 6 months Yes

Secondary:

• To obtain preliminary evidence of biologic activity of these four orally administered 6 months No
• to evaluate and document side effects from chronic administration of these four drugs at the doses prescribed in this protocol 6 months Yes
• to evaluate different radiographic techniques as markers of tumor response. 6 months No

Inclusion Criteria:

• Patients with relapsed or progressive poor prognosis tumors for which no curative therapy exists.
• Histologic confirmation of disease at diagnosis or relapse.
• Brain stem glioma patients who have progressed after radiation therapy do not require histologic confirmation. Duration of symptoms at the time of diagnosis must be less than 3 months and should consist of cranial nerve deficits and/or ataxia and/or long tract signs.
• Prior radiation therapy and/or chemotherapy are permitted.
• Karnofsky Performance Status >50. For infants, the Lansky play scale >50% can be substituted.
• Life expectancy > 2 months.
• No active uncontrolled cardiac, hepatic, renal, or psychiatric disease defined as ≥ grade 3 based on the common toxicity criteria.
• No known allergies to sulfonamides
• Adequate renal function: Serum Creatinine < 1.5 mg/dl or creatinine clearance or GFR >
• 70 ml/min.
• Adequate hepatic function: Total Bilirubin < 1.5 mg/dl; SGOT, SGPT, Alk Phos < 3x normal.(SGOT can be < 4x normal for patients on Zantac).
• Adequate bone marrow reserve: Hgb > 9.0 g/dl, Platelets > 75,000/mm3 (transfusion independent),WBC > 2000/mm3 and ANC > 1000/mm3.
• Patients receiving steroids and/or anti-seizure medications are eligible for this study.

Exclusion Criteria:

• Patients must not be pregnant or nursing, and all patients of child bearing age (both male and female) must be willing to practice birth control during and for 2 months after treatment with thalidomide. If the patient is unable to use oral contraceptives for medical reasons, 2 different barrier methods may be used if approved by the treating physician.
• No concurrent use of other investigational agents.
• Patients that have received more than 2 months of oral therapy with any of the agents used in this study will be ineligible. Standard administration of IV etoposide and cyclophosphamide, usually administered in 3-week cycles is permitted.

Lead Sponsor: Dana-Farber Cancer Institute

Dana-Farber Cancer Institute

Boston Massachusetts 02115 United States

Overall Clinical Trial Officials and Contacts

Mark W. Kieran, MD, PhD Principal Investigator Dana-Farber Cancer Institute  

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00165451

Study ID Number: 01-046

ClinicalTrials.gov Identifier: NCT00165451

Health Authority: United States: Food and Drug Administration