Advertisement

Topics

A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas

2014-08-27 03:13:21 | BioPortfolio

Summary

Background:

- Vorinostat and bortezomib are anti-tumor drugs that have been approved by the Food and Drug Administration to treat different kinds of myeloma and lymphoma in adults. The combination of these two drugs has been tried in a small number of adults, but it has not been formally approved and is experimental, particularly in children. Researchers are interested in determining safe and effective treatment doses of vorinostat and bortezomib in children, and learning more about how these drugs affect tumor growth and human development.

Objectives:

- To determine safe and effective doses of vorinostat and bortezomib to treat solid tumors in children.

- To study the effects of vorinostat and bortezomib on blood cells, blood flow, and human development.

Eligibility:

- Children, adolescents, and young adults between 1 and 21 years of age who have been diagnosed with solid tumors that have not responded to treatment.

Design:

- Eligible participants will be screened with a physical examination, blood and tumor samples, and imaging studies.

- Participants will have 21-day treatment cycles of vorinostat and bortezomib. Vorinostat will be given as either tablets or liquid doses on days 1 through 5 and 8 through 12 of each cycle. Bortezomib will be given as an intravenous injection on days 1, 4, 8, and 11 of each cycle. Participants will keep a drug administration diary to record information about side effects or other problems with the treatment.

- Participants may continue to receive vorinostat and bortezomib for up to 2 years unless serious side effects develop or the tumor does not respond to treatment.

- Additional blood samples will be taken at regular intervals for the first 3 days after the first bortezomib dose and for the first 2 days after the first vorinostat dose of the first treatment cycle.

Description

Background:

-The combination of vorinostat and bortezomib has been shown to be synergistic in vitro in a variety of malignancies, including hepatoma, multiple myeloma, leukemia, lymphoma, and gastrointestinal cancer. Currently several phase 2 adult studies are underway evaluating combination therapy.

Objectives:

- To determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of the combination of oral vorinostat administered on days 1-5 and 8-12 and bortezomib administered intravenously on days 1, 4, 8, 11, every 21 days to children with refractory or recurrent solid tumors.

- To define and describe the toxicities of vorinostat in combination with bortezomib administered on this schedule.

- To characterize the pharmacokinetics of vorinostat and bortezomib in combination in children with refractory or recurrent solid tumors.

- Secondary objectives include preliminary definition of the antitumor activity of these agents when administered together; and assessment of the biologic activity of bortezomib by measuring NF-kappaB activity in peripheral blood mononuclear cells (PBMC) and by measuring endoplasmic reticulum stress response using the GRP78 molecular chaperone marker in PBMC.

Eligibility:

- Patients greater than12 months and less than or equal to 21 years of age with a diagnosis and histologic verification (except patients with instrinsic brain stem tumors, optic pathway gliomas or pineal tumors) of measureable or evaluable relapsed or refractory solid tumors including CNS tumors and lymphomas are eligible. Current disease state must be one for which there is no known curative therapy, or therapy proven to prolong survival.

- Performance score: Karnofsky greater than or equal to 60% for patients greater than 16 years of age; Lansky greater than or equal to 60 for patients less than or equal to 16 years of age.

- Must have fully recovered from acute toxic effects from all prior therapy which have been completed within the specified prior time frame. Have adequate organ function as determined by laboratory evaluation.

Design:

- This is a phase I study of vorinostat administered orally once daily on days 1-5 and day 8-12 in combination with bortezomib administered intravenously on days 1, 4, 8, and 11 of a 21 day cycle. Disease evaluation will be performed after cycle 1 and then every 2 cycles thereafter.

- Therapy may continue for up to 2 years in the absence of progressive disease or unacceptable toxicity.

- Optional participation in correlative biology studies or pharmacokinetic studies will be offered.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Lymphoma

Intervention

Vorinostat (SAHA), Velcade (PS-341, Bortezomib)

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:13:21-0400

Clinical Trials [1973 Associated Clinical Trials listed on BioPortfolio]

Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant for Non-Hodgkin Lymphoma

RATIONALE: Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells and make them more likely to die. Giving bortezomib together with vorinostat after an autologou...

Phase 1b Lymphoma Study of AMG 655 in Combination With Bortezomib or Vorinostat

This is a multi-center, phase 1b study of AMG 655 in combination with bortezomib or vorinostat in subjects with relapsed or refractory low grade lymphoma, mantle cell lymphoma, diffuse lar...

Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma

RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat may kill more ca...

Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

This phase I trial is studying the side effects and best dose of vorinostat when given together with bortezomib in treating young patients with refractory or recurrent solid tumors, includ...

VELCADE in Subjects With Relapsed or Refractory Mantle Cell Lymphoma

The purpose of this study is to find out whether treatment with VELCADE will increase the time it takes for lymphoma to get worse.

PubMed Articles [1004 Associated PubMed Articles listed on BioPortfolio]

Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma.

Although the outcomes of patients with mantle cell lymphoma (MCL) have improved, there is still no cure. Bortezomib has a 33% response rate in relapsed/refractory MCL and has shown additive and/or syn...

Unified D-α-Tocopherol 5-Fu/SAHA bioconjugates self-assemble as complex nanodrug for optimized combination therapy.

To optimize the synergistic efficacy of combination therapy with controlled molar ratio, complex small molecule-based nanodrug (Co-SMND) of 5-fluorouracil (5-Fu)/vorinostat (SAHA) was developed.

Successful Use of Bortezomib-Lenalidomide Combination as Treatment for a Patient With Plasmablastic Lymphoma.

Tolerance, Kinetics, and Depth of Response for Subcutaneous Versus Intravenous Administration of Bortezomib Combination in Chinese Patients With Newly Diagnosed Multiple Myeloma.

Peripheral neuropathy (PN) is an important toxicity that limits the use of bortezomib (Btz). Attempts to reduce PN have included its subcutaneous (SC) administration.

An Expanded Treatment Protocol of Panobinostat Plus Bortezomib and Dexamethasone in Patients With Previously Treated Myeloma.

Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received...

Medical and Biotech [MESH] Definitions

A pyrazine and boronic acid derivative that functions as a reversible PROTEASOME INHIBITOR. It is used as an ANTINEOPLASTIC AGENT in the treatment of MULTIPLE MYELOMA and MANTLE CELL LYMPHOMA.

A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.

B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.

A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.

Two or more distinct types of malignant lymphoid tumors occurring within a single organ or tissue at the same time. It may contain different types of non-Hodgkin lymphoma cells or both Hodgkin and non-Hodgkin lymphoma cells.

More From BioPortfolio on "A Phase I Study of Vorinostat and Bortezomib in Children With Refractory of Recurrent Solid Tumors, Including CNS Tumors and Lymphomas"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Food
Food is any substance consumed to provide nutritional support for the body. It is usually of plant or animal origin, and contains essential nutrients, such as carbohydrates, fats, proteins, vitamins, or minerals. The substance is ingested by an organism ...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...


Searches Linking to this Trial