Weekly Vinblastine for Chemotherapy Naive Children With Progressive Low Grade Glioma (PLGGs)

Phase 2

• Conditions: Glioma
• Interventions: Drug: Vinblastine Sulphate

• Registration Number: NCT00575796
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

The overall objective of this study is to determine the efficacy of weekly Vinblastine in chemotherapy naïve patients with progressive or incompletely resected paediatric low grade glioma, to generate estimates of the response rate, progression-free survival, toxicity and quality of daily living among the population treated and determine biologic factors which will enable us to predict tumour behaviour.

Detailed Description

Unresectable low grade glioma (LGG) of childhood increasingly appears as a chronic condition for which multiple treatments may be required. While several studies have shown evidence of short term tumour control with chemotherapy, the progression-free survival at 5 years is unsatisfactory. In addition, several regimens currently used for this condition are associated with significant risks of side effect and long term toxicity.

We have piloted in a single arm study the feasibility and efficacy of Vinblastine for children with recurrent and refractory low grade glioma, who have failed at least one line of treatment (chemotherapy and/or irradiation). Preliminary results show promising activity with minimal toxicity.

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-12-14
• Study First Submitted QC: 2007-12-14
• Study First Posted: 2007-12-18
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-19
• Last Update Posted: 2017-09-20
• Primary Completion: 2018-10
• Study Completion: 2019-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Patients must have been < 18 years of age when originally diagnosed.

2. Histologic Diagnosis: Patients must have histologic verification of LGG at original diagnosis. Exceptions are optic pathway gliomas in children with neurofibromatosis or children with large hypothalamic tumours for which a diagnostic biopsy does not seem necessary. Patients with disseminated low grade glioma are eligible.

   1. Astrocytoma Variants: fibrillary, protoplasmic, gemistocytic, mixed
   2. Pilocytic Astrocytoma
   3. Pleomorphic Xanthoastrocytoma
   4. Infantile desmoplastic astrocytoma
   5. Ganglioglioma
   6. Oligodendroglioma
   7. Mixed glioma (including oligo-astrocytoma)
   8. Pilomyxoid astrocytoma

3. Performance Level :Patients must have an ECOG performance status of 0, 1 or 2 or a Lansky/Karnofsky score > 50

4. Life expectancy: Patients must have a life expectancy of * 2 months.

5. Prior Therapy: Patients are eligible at the time of diagnosis or first progression following treatment with surgery only.

6. Measurable Disease: Patients must have measurable disease, documented by radiographic criteria.

7. Concomitant Medications

   1. Steroids: Steroids may be used at the time of inclusion to control progressive symptoms.
   2. Anti-epileptic medications are permitted - levetiracetam (Keppra) or clobazam (Frisium) being the preferred anti-epileptic medications for chronic use reserving phenytoin and lorazepam for acute seizure control.

8. Organ Function Requirements: All patients must have adequate organ and bone marrow function within 7 days of starting chemotherapy (ANC * 1.0 x 109/L /, and platelet count * 100 x 109/L (transfusion independent).

9. Regulatory: All patients and/or their parents or legal guardians must sign a written informed consent and all institutional requirements for human studies must be met. This study is open to all participants regardless of gender or ethnicity.

Exclusion Criteria

Inclusion criteria are restrictive. Patient must meet all inclusion criteria.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Vinblastine Sulphate	Children will be treated with Vinblastine Sulphate chemotherapy via intravenous administration once a week over a period of 26 weeks. MRI disease evaluation should be performed at weeks 12 and 26 (+/- 1 week). If response on MRI at week 26 \> stable (i.e. stable disease, objective or partial or complete response compared to the baseline MRI exam), continue weekly Vinblastine to the total duration of treatment (i.e. 70 weeks). All children will be followed until they demonstrate clear signs tumour progression.

Primary Outcome Measures

Name	Time	Method
The response rate to weekly vinblastine	70 Weeks

Secondary Outcome Measures

Name	Time	Method
The progression-free survival with Vinblastine	At one year, two years and three years
The quality of daily life during treatment	26 Weeks
The correlation of biological features of LGG with tumour behaviour	5 years
To determine the role of telomere maintenance in the prognosis and evolution of PLGG	5 years

Trial Locations

Locations (17)

Saskatoon Cancer Center; 🇨🇦 Saskatoon, Saskatchewan, Canada

Children's and Women's Health Centre of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada

IWK Health Centre; 🇨🇦 Halifax, Nova Scotia, Canada

Montreal Children's Hospital; 🇨🇦 Montreal, Quebec, Canada

Janeway Child Health Centre; 🇨🇦 St. John's, Newfoundland and Labrador, Canada

Stollery Children's Hospital; 🇨🇦 Edmonton, Alberta, Canada

Alberta Children's Hospital; 🇨🇦 Calgary, Alberta, Canada

Allan Blair Cancer Centre; 🇨🇦 Regina, Saskatchewan, Canada

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

Centre Hospitalier Universitaire de Quebec; 🇨🇦 Sainte-Foy, Quebec, Canada

Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

Children's Hospital of Western Ontario; 🇨🇦 London, Ontario, Canada

Children's Hospital of Eastern Ontario; 🇨🇦 Ottawa, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Hospital Sainte-Justine; 🇨🇦 Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada

McMaster University; 🇨🇦 Hamilton, Ontario, Canada