Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma

• ClinicalTrials.gov Identifier: NCT00098865
• Recruitment Status: Completed
• First Posted: December 9, 2004
• Results First Posted: September 25, 2014
• Last Update Posted: October 7, 2014
• Sponsor: Dana-Farber Cancer Institute
• Collaborators: National Cancer Institute (NCI); Boston Children's Hospital; Celgene Corporation
• Information provided by (Responsible Party): Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute

Study Description

Brief Summary:

RATIONALE: Thalidomide may stop the growth of tumor cells by stopping blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with temozolomide may kill more tumor cells.

PURPOSE: This phase II trial is studying the effectiveness of combining thalidomide with temozolomide in treating young patients who have relapsed or progressive brain tumors or recurrent neuroblastoma.

Condition or disease	Intervention/treatment	Phase
Central Nervous System Tumor, Pediatric; Neuroblastoma	Drug: temozolomide; Drug: thalidomide	Phase 2

Detailed Description:

OBJECTIVES:

Primary

• Determine the feasibility of thalidomide and temozolomide in pediatric patients with relapsed or progressive poor prognosis brain tumors or recurrent neuroblastomas.

Secondary

• Determine preliminarily evidence of biologic activity of this regimen in these patients.
• Determine the toxic effects of this regimen in these patients.

STATISTICAL DESIGN: The primary data analysis will estimate the percentage of patients who can complete 6 months of therapy in the mixed population. With a target accrual of 20 patients the 90% confidence for the true feasibility rate will be no wider than 40%.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Pilot Study Of Thalidomide With Temozolomide In Patients With Relapsed Or Progressive Brain Tumors Or Neuroblastoma
• Study Start Date: September 2002
• Actual Primary Completion Date: June 2010
• Actual Study Completion Date: June 2010

Arms and Interventions

Arm

Intervention/treatment

Experimental: Thalidomide and Temozolomide; Thalidomide: Oral thalidomide on days 1-28 of a 28 day cycle initiated at 3 mg/kg and increased to maximum dose of 24 mg/kg or 1000 mg as tolerated. Temozolomide: Oral temozolomide on days 1-5 of 28 day cycle given at 200 mg/m2 or 150 mg/m2 for patients who had previously received significant therapy to the bone marrow (chemotherapy or radiation) or cranial spinal radiation. Patients were treated for 6 cycles unless disease progression or excessive toxicity. Treatment could continue beyond 6 cycles if absent disease progression

Drug: temozolomide; The lower 150/m2 Temozolomide dose was for patients who had previously received significant therapy to the bone marrow (chemotherapy or radiation) or cranial spinal raditation.; Other Name: Temodar; Drug: thalidomide; Calculated dose was rounded down to the nearest 50mg, or up to 50mg if calculated dose was less than 50mg. Patients increased the daily dose by 50mg (one capsule) on a weekly basis unitl either unacceptable toxicity or a maximum dose.; Other Name: Thalamid

Outcome Measures

Primary Outcome Measures :

1. Therapy Completion Rate [ Time Frame: 6 months ]
   Feasibility in this study was defined as completion of 6 months of thalidomide with temozolomide therapy. The corresponding therapy completion rate is defined as the proportion of patients who completed 6 months of therapy.

Secondary Outcome Measures :

1. Overall Response [ Time Frame: Assessed every 8 weeks while on treatment and every 3 months for one year off-study ]

   Overall response is the best response during 6 months of therapy measured by radiographic response.

   Complete Response (CR): Disappearance of all detectable tumors by imaging, if initially positive, as well as 2 consecutively negative CSF cytologic examinations (if the initial cytology was positive).

   Partial Response (PR): > 50% reduction in the sum of the products of the maximum perpendicular diameter of all measurable lesions; or 2 consecutively negative CSF cytologies and a < 50% reduction in tumor size.

   Stable Disease (SD): < 50% reduction in the sum of the products of the maximum perpendicular diameters of all measurable lesions, and persistently negative or positive CSF cytology Progressive Disease (PD): > 25% increase in the size of any measurable lesion, the appearance of a new radiographically demonstrable lesion, or the conversion of negative CSF cytology to positive, as confirmed by at least one repeat CSF cytology

2. Overall Survival [ Time Frame: Assessed after treatment discontinued every 3 months up to 2 years. ]
   Time from registration to death. Patients alive at last follow-up were censored.

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed* diagnosis of 1 of the following:

  • Poor prognosis brain tumor

    • Relapsed or progressive disease
    • No curative therapy exists

  • Neuroblastoma

    • Recurrent disease NOTE: *Histologic confirmation not required for brain stem glioma; patients with brain stem glioma must have clinical and radiographic evidence of disease
• Patients with brain stem glioma must have symptoms lasting < 3 months comprising cranial nerve deficits (often VI or VII) and/or ataxia and/or long tract signs

PATIENT CHARACTERISTICS:

Age

• 21 and under

Performance status

• Karnofsky 50-100% OR
• Lansky 50-100%

Life expectancy

• More than 2 months

Hematopoietic

• Hemoglobin ≥ 9.0 g/dL
• Platelet count > 75,000/mm^3
• WBC > 2,000/mm^3
• Absolute neutrophil count > 1,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• SGOT and SGPT ≤ 2 times normal (SGOT ≤ 4 times normal for patients taking Zantac)
• Alkaline phosphatase ≤ 2 times normal
• No active hepatic disease ≥ grade 3

Renal

• Creatinine < 1.5 mg/dL OR
• Creatinine clearance ≥ 70 mL/min
• No active renal disease ≥ grade 3

Cardiovascular

• No active cardiac disease ≥ grade 3

Pulmonary

• No active pulmonary disease ≥ grade 3

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 4 weeks after study participation

  • Willing and able to participate in the System for Thalidomide Education and Prescription Safety (S.T.E.P.S.^®) program
• No active psychiatric disease ≥ grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed

  • No prior thalidomide

Chemotherapy

• Prior chemotherapy allowed

  • No prior temozolomide

Endocrine therapy

• Concurrent steroids allowed

Radiotherapy

• Prior radiotherapy allowed

Surgery

• Prior surgery allowed

Other

• Concurrent antiseizure medications allowed
• No other concurrent investigational agents

Contacts and Locations

Locations

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Dana-Farber Cancer Institute

National Cancer Institute (NCI)

Boston Children's Hospital

Celgene Corporation

Investigators

• Study Chair: Mark W. Kieran, MD, PhD; Dana-Farber Cancer Institute

More Information

• Responsible Party: Mark W. Kieran, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00098865
• Other Study ID Numbers: 01-279 DFCI; P30CA006516 ( U.S. NIH Grant/Contract ); CDR0000396780 ( Registry Identifier: NCI PDQ )
• First Posted: December 9, 2004
• Results First Posted: September 25, 2014
• Last Update Posted: October 7, 2014
• Last Verified: September 2014

Additional relevant MeSH terms:

Neuroblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms by Site; Nervous System Diseases; Thalidomide; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Leprostatic Agents; Anti-Bacterial Agents; Anti-Infective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors