Clinical trial NCT00165451: A Trial of Thalidomide, Celecoxib, Etoposide and Cyclophosphamide in Patients With Relapsed or Progressive Cancer
Official title: Anti-Angiogenic Chemotherapy: A Phase II Trial of Thalidomide, Celecoxib, Etoposide and Cyclophosphamide in Patients With Relapsed or Progressive Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Keywords: Relapsed tumors
Progressive Poor Prognosis Tumors
Thalidomide
Celecoxib
Etoposide
Cyclophosphamide
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2005-09-14
Enrollment: 20
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: To evaluate the feasibility of administering thalidomide, celecoxib, etoposide and cyclophosphamide for recurrent and poor prognosis tumors.
timeFrame: 6 months
Secondary outcomes:
measure: To obtain preliminary evidence of biologic activity of these four orally administered
timeFrame: 6 months
measure: to evaluate and document side effects from chronic administration of these four drugs at the doses prescribed in this protocol
timeFrame: 6 months
measure: to evaluate different radiographic techniques as markers of tumor response.
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Mark W. Kieran, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kieran MW, Turner CD, Rubin JB, Chi SN, Zimmerman MA, Chordas C, Klement G, Laforme A, Gordon A, Thomas A, Neuberg D, Browder T, Folkman J. A feasibility trial of antiangiogenic (metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer. J Pediatr Hematol Oncol. 2005 Nov;27(11):573-81. doi: 10.1097/01.mph.0000183863.10792.d4.