Topics

Cabozantinib in Combination With 13-cis-Retinoic Acid in Children With Relapsed or Refractory Solid Tumors

2018-08-07 16:31:12 | BioPortfolio

Summary

This study is being conducted in order to determine the safety, dose-limiting toxicities, and maximum tolerated dose of cabozantinib in combination with 13-cis-retinoic acid in patients with relapsed or refractory solid tumors including tumors of the central nervous system (CNS)

Description

Participants will be treated in an open-label, non-randomized phase I trial to determine the safety, dose-limiting toxicities, tolerability, and maximum tolerated dose of cabozantinib combined with 13-cis-retinoic acid in children with relapsed or refractory solid tumors.

Eligible Participants must have a histologically confirmed solid tumor at time of initial diagnosis, and have either progressive, recurrent, or refractory disease. Cabozantinib will be given orally once every day with cycles repeated every 4 weeks (28 days, +/- 3 days), with no rest periods between cycles, combined with 13-cis-retinoic acid at 80mg/m2/dose twice daily for two consecutive weeks (14 days) out of every four weeks (28 days, +/- 3 days). Participants with disease response or stable disease at the end of each cycle will be allowed to continue treatment, and patients may continue to receive therapy until there is evidence of clinical or radiographic disease progression.

The investigator will perform a phase I trial to define the maximum tolerated dose (MTD) of cabozantinib in combination with 13-cis-retinoic acid using the standard 3+3 study design. Cohorts of patients will be enrolled at doses determined as detailed below. The first cycle will be used to determine the dose-limiting toxicities. Toxicity will be summarized by dose levels. Response rates will be estimated. Kaplan-Meier curves will be plotted to graphically present time to progression (PFS) and other time-to-event endpoints. Median PFS and the corresponding 95% confidence intervals will be reported.

Cabozantinib dosing will be started and modified, if necessary, during the course of the trial as detailed below. The tablet formulation of the drug will be used with doses in 20mg increments.

Baseline evaluation to determine eligibility will include medical history (including a review of current medications), physical examination, blood count with differential, chemistry panel blood or urine pregnancy test for women of child-bearing potential (not post-menopausal for at least 12 months and not surgically sterile), echocardiogram, electrocardiogram, and disease evaluation (appropriate for disease). Samples for correlative studies will be collected accordingly.

Participants will be evaluated weekly (+/- three days) during the first cycle. The interim evaluations will consist of interval history (with a review of current medications), physical examination, blood count with differential, and chemistry panel. Pregnancy tests will be performed prior to each cycle in women of childbearing potential. After the first cycle, patients will be evaluated monthly (+/- seven days).

Participants who have had therapy discontinued will undergo end-of-therapy evaluations and will continue to be monitored with interval histories, physical examinations, and laboratory evaluations every three months (+/- seven days), with disease evaluations every three months (+/- 28 days) until they fulfill criteria for removal from study or the study is completed

Study Design

Conditions

Solid Tumor

Intervention

Cabozantinib, 13-cis-retinoic acid

Location

UC San Diego Moores Cancer Center
La Jolla
California
United States
92093

Status

Not yet recruiting

Source

University of California, San Diego

Results (where available)

View Results

Links

Published on BioPortfolio: 2018-08-07T16:31:12-0400

Clinical Trials [3654 Associated Clinical Trials listed on BioPortfolio]

Cabozantinib-S-Malate in Treating Patients With Advanced Solid Tumors and Human Immunodeficiency Virus

This phase I trial studies the side effects and best dose of cabozantinib-s-malate in treating patients with advanced solid tumors and human immunodeficiency virus. Cabozantinib-s-malate m...

A Phase II Trial of All-Trans-Retinoic Acid in Combination With Interferon-Alpha 2a in Children With Recurrent Neuroblastoma or Wilms' Tumor

A body of preclinical data has provided a strong rationale for evaluating the combination of IFN-alpha with retinoic acid. The two drugs have different mechanisms of action and, when used...

A Phase I Trial of Tamoxifen and 9-Cis-Retinoic Acid in Breast Cancer Patients

This is a dosage escalation study to estimate the maximum tolerated dose of 9-cis-retinoic acid given in combination with tamoxifen. Groups of 3 to 6 patients receive oral 9-cis-retinoic ...

ZD6474 Alone and in Combination With Retinoic Acid in Pediatric Neuroblastoma

The goal of this clinical research study is to find the highest safe dose of the drug ZactimaTM (ZD6474) in patients with neuroblastoma or medulloblastoma that has gotten worse, has come b...

RA-4: 13-cis Retinoic Acid for Treatment of Men With Azoospermia

Men with infertility and normal hormone levels have few options for fertility treatment. Previous research suggests that men with infertility may have low levels of the active form of Vita...

PubMed Articles [15043 Associated PubMed Articles listed on BioPortfolio]

Phase I trial of belinostat in combination with 13-cis-retinoic acid in advanced solid tumor malignancies: a California Cancer Consortium NCI/CTEP sponsored trial.

The reported maximum tolerated dose (MTD) of single-agent belinostat is 1000 mg/m given days 1-5, every 21 days. Pre-clinical evidence suggests histone deacetylase inhibitors enhance retinoic acid s...

Role of mitochondria and cardiolipins in growth inhibition of breast cancer cells by retinoic acid.

All-trans-retinoic-acid (ATRA) is a promising agent in the prevention/treatment of breast-cancer. There is growing evidence that reprogramming of cellular lipid metabolism contributes to malignant tra...

All-trans retinoic acid induces anti-tumor effects via STAT3 signaling inhibition in oral squamous cell carcinoma and oral dysplasia.

Oral squamous cell carcinoma (OSCC), which may arise from oral dysplasia, is one of the most prevalent cancers around the world. In recent years, all-trans retinoic acid (ATRA) has showed great potent...

Post-translational modification of retinoic acid receptor alpha and its roles in tumor cell differentiation.

Retinoic acid (RA) is a well-known differentiation inducer that exerts its effects by binding to nuclear RA receptors. Retinoic acid receptor α (RARα), as an important nuclear RA receptor, is activa...

Targeting and microenvironment-improving of phenylboronic acid-decorated soy protein nanoparticles with different sizes to tumor.

It is essential for nanoparticles to delivery drugs accurately and penetrate deeply to tumor. However, complicated tumor microenvironment such as elevated tumor interstitial fluid pressure (IFP) and s...

Medical and Biotech [MESH] Definitions

Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.

A cytochrome P450 enzyme that resides in the ENDOPLASMIC RETICULUM. It catalyzes the conversion of trans-RETINOIC ACID to 4-hydroxyretinoic acid.

A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signalling pathways.

A cytochrome P450 enzyme family whose members function in the metabolism of RETINOIC ACID. It includes RETINOIC ACID 4-HYDROXYLASE.

A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.

More From BioPortfolio on "Cabozantinib in Combination With 13-cis-Retinoic Acid in Children With Relapsed or Refractory Solid Tumors"

Quick Search

Relevant Topics

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Pediatrics
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...


Searches Linking to this Trial