Study of Vinblastine and Sirolimus in Children With Recurrent/Refractory Solid Tumours Including CNS Tumours

NCT01135563 | Completed Phase 1 DMC

• 1 other identifier: 1000016324
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 5

Brief Summary

This study is a Phase I study using vinblastine and sirolimus in patients with relapsed solid tumors including selected brain tumors and lymphoma. The investigators hypothesis is that the combination administration of weekly vinblastine and sirolimus is safe.

Conditions

Solid Tumors; Central Nervous System Tumors

Keywords

pediatrics; Solid Tumors; CNS Tumors; Vinblastine; Sirolimus; Recurrent; Refractory

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of vinblastine in combination with sirolimus

  Maximum tolerated dose (as defined by protocol) of vinblastine in combination with sirolimus

  12 months

Secondary Outcomes (2)

• Safety data

  12 months

• Response Rate

  12 months

Study Arms (1)

Vinblastine and Sirolimus

EXPERIMENTAL

The standard 3+3 Phase 1 trial design will be used for the conduct of this study. Three to six patients can be concurrently enrolled onto a dose level. Accrual is suspended when a cohort of three has been enrolled until toxicity data for that cohort have been reported, or when the study endpoints have been met.

Drug: Vinblastine and Sirolimus

Interventions

Vinblastine and Sirolimus DRUG

Patients will be enrolled to receive vinblastine and sirolimus in 28 day cycles. Using the 3+3 standard Phase1 design, vinblastine will be administered via IV push on Days 1, 8, 15, 22. The starting dose of 4 mg/m2 (Dose Level 1) is 67% of the established MTD (6 mg/m2) for this schedule in pediatrics. Dose escalation will take place in a standard 3+3 design, in which doses will increase by approximately 20 to 25% in successive 3-patient cohorts. Sirolimus (rapamycin) will be given by mouth (tablet or suspension) once daily throughout the cycle. Ideally patients will remain on the same dose form (tablet or suspension) for the duration of the study. All patients will be assigned a target sirolimus serum trough

Also known as: Vinblastine Sulfate Injection, Rapamune

Vinblastine and Sirolimus

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: 0-21 years at the time of diagnosis
• Diagnosis: Histologic verification at either the time of original diagnosis or relapse of solid tumor including CNS tumors or lymphomas
• Disease Status: All refractory/recurrent solid tumors including CNS tumors (all Diffuse Intrinsic Brain Stem Gliomas excluded) and lymphomas that have relapsed after, or are refractory to, a chemotherapy-containing treatment regimen
• Measurable disease:
• Measurable tumor by CT or MRI defined as \>10 mm by spiral CT in at least one dimension
• Current disease state must be one for which there is currently no known curative therapy
• A negative urine pregnancy test is required for female participants of child bearing potential
• Organ Function Requirements:
• adequate liver function as defined by AST or ALT \< 5 x upper limit of normal, bilirubin ≤1.5 X upper limit of normal
• adequate renal function: Serum creatinine \< 1.5 X upper limit of normal for age
• Adequate Bone Marrow Function Defined as:
• ANC ≥ 1000/mm3, platelets ≥ 75,000/mm3 and hemoglobin ≥ 90 g/L
• Transfusions are permitted to meet these platelet and Hgb criteria, if the patient is known to have a history of bone marrow involvement with tumor
• Patients with platelet counts \< 75,000/ mm3 who are refractory to platelet transfusions are not eligible for this study
• Patients requiring transfusions of platelets or RBC to meet eligibility criteria will not be evaluable for platelet or hgb/hct hematological toxicity

You may not qualify if:

• Lansky score \<50%
• Investigational Drugs: Patients who are currently receiving another investigational drug(s)
• Previous treatment with Vinblastine and/or mTor inhibitors
• Anti-cancer Agents: Patients who are currently receiving other anticancer agents. Patients must have fully recovered from the effects of prior chemotherapy, generally at least 3 weeks from the most recent administration (6 weeks for nitrosoureas)
• Infection: Patients who have an uncontrolled infection are not eligible until the infection is judged to be well controlled
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal
• One week from usage of hematopoietic Growth Factor
• Patients who are refractory to platelet transfusions
• Brain Stem Glioma patients

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Solving Kids' Cancer: collaborator

Study Sites (5)

Rady Children's Hospital-San Diego

San Diego, California, 92123, United States

Location

SSM Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Related Publications (1)

• Morgenstern DA, Marzouki M, Bartels U, Irwin MS, Sholler GL, Gammon J, Yankanah R, Wu B, Samson Y, Baruchel S. Phase I study of vinblastine and sirolimus in pediatric patients with recurrent or refractory solid tumors. Pediatr Blood Cancer. 2014 Jan;61(1):128-33. doi: 10.1002/pbc.24656. Epub 2013 Aug 17.

  PMID: 23956145 BACKGROUND

MeSH Terms

Conditions

Central Nervous System Neoplasms; Recurrence

Interventions

Vinblastine; Sirolimus

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Macrolides; Lactones; Organic Chemicals

Study Officials

• Sylvain Baruchel, MD

  The Hospital for Sick Children, Toronto Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Staff Oncologist

Study Record Dates

• First Submitted: June 1, 2010
• First Posted: June 2, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: September 20, 2019

Record last verified: 2019-09

Locations

CA (2); US (3)