A Trial of Thalidomide, Celecoxib, Etoposide and Cyclophosphamide in Patients With Relapsed or Progressive Cancer

Condition(s) targeted: Neoplasms

Intervention: Thalidomide (Drug); Celecoxib (Drug); Etoposide (Drug); Cyclophosphamide (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Mark W. Kieran, MD, PhD, Principal Investigator, Affiliation: Dana-Farber Cancer Institute

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.

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

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

Primary outcome: To evaluate the feasibility of administering thalidomide, celecoxib, etoposide and cyclophosphamide for recurrent and poor prognosis tumors.

Secondary outcome:

To obtain preliminary evidence of biologic activity of these four orally administered

to evaluate and document side effects from chronic administration of these four drugs at the doses prescribed in this protocol

to evaluate different radiographic techniques as markers of tumor response.

Detailed description:

- 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.

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

Criteria:

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.

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States

Starting date: June 2001
Ending date: October 2006
Last updated: December 21, 2007