Pre-operative RT and TMZ in Patients With Newly Diagnosed GBM Diagnosed Glioblastoma. A Phase I Study. (PARADIGMA)

NCT03480867 | Withdrawn Phase 1 DMC

• 1 other identifier: MUHC-2016-1524
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Glioblastoma (GBM) is the most common primary brain cancer in adults. Despite surgery, conventional radiotherapy, and chemotherapy, the average survival for GBM is 15-16 months. Although additional chemoradiotherapy has been shown to increase survival, the majority recur at the original location. Despite many efforts to improve the local control by improving surgical techniques, increasing the radiotherapy dose or adding newer chemotherapy agents, these attempts have failed to show a survival benefit or an improved cancer control. People who are not participating in a study are usually treated with surgery followed by radiation (6 weeks duration) together with temozolomide (chemotherapy drug) followed by temozolomide alone. For patients who receive this usual treatment approach for this cancer, about 4 out of 100 are free of cancer growth five years later. Because GBM invades the surrounding normal brain, this study is looking into the possibility of minimizing invasion by starting treatment using the combination of radiotherapy and chemotherapy prior to surgery. This approach is an experimental form of treatment and the diagnosis is based exclusively on imaging and not on histology of the tumour tissue, and there is a possibility that your tumor may not be a GB but of other origins.

Conditions

Glioblastoma Multiforme, Adult

Outcome Measures

Primary Outcomes (1)

• To assess toxicity of the regimen

  Toxicity will be assessed and graded using CTCAE V. 4.03

  one year

Secondary Outcomes (1)

• Number of patients completing the study treatment

  one year.

Study Arms (1)

Pre-operative RT and TMZ

EXPERIMENTAL

* Single Arm: Pre-operative Radiation +Temozolomide followed by Surgery plus six cycles of Temozolomide

Drug: Temozolomide; Radiation: Pre-Operative Radiation

Interventions

Temozolomide DRUG

Experimental: Registered one arm study Seven days of pre-operative Radiation+Temozolomide followed by surgery plus TMZ, as adjuvant component.for six cycles.

Also known as: Surgery

Pre-operative RT and TMZ

Pre-Operative Radiation RADIATION

Radiation is given with Temozolomide for 7 days before surgery

Pre-operative RT and TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed (MR image-based) GBM - Must be able to undergo gadolinium-enhanced MRI.
• Must be a candidate for radical surgical resection in the opinion of the neurosurgeon.
• The tumor must measure less than 6 cm in maximum diameter. The tumor diameter will be the greatest diameter as measured on the contrast-enhanced MRI.
• A neurosurgical oncologist, radiation oncologist and neuro-oncologist will assess each patient in advance of enrollment.
• The estimated post-surgical radiation field must be compatible with the proposed radiation scheme - ie, to ensure a safe radiation margin from structures such as the optic apparatus and brain stem.
• The GBM tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)
• Age\>18years
• Karnofsky Performance Status (KPS) 70.
• History and physical examination within 14 days from start of therapy, including documentation of steroid dose.
• Adequate complete blood counts (Absolute neutrophil count (ANC) .:! 1,800. cells/mm3; Platelets.:! 100,000 cells/mm3; Hemoglobin.:! 10.0 g/dl), renal and liver function within 14 days prior to therapy with values\< 3x (upper limit normal) ULN.
• For females of child-bearing potential, negative serum pregnancy test within 14 days prior to therapy and use of contraception.
• Signed consent form.

You may not qualify if:

• Tumors within 1 cm from critical structures (brainstem, optic apparatus), or with massive edema, or with the possibility of herniation, or any tumor that in the neurosurgeon's opinion would be considered unsafe to delay surgery or is not grossly resectable.
• Prior invasive malignancy (except for non-melanomatous skin cancer, non- invasive bladder cancer, and non-invasive cervix cancer) unless disease free for 2:5 years.
• Recurrent or multifocal GBM.
• Any site of metastatic disease (drop metastases).
• Prior chemotherapy or radiation therapy to the head or neck (except for T1 glottic tumor
• Severe active co-morbid medical condition as assessed by medical team.
• Patients enrolled in any other protocol.
• Inability to undergo MRI.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Centre-Cedars Cancer Centre

Montreal, Québec, Canada, H4A 3J1, Canada

Location

Related Publications (20)

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MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Valerie Panet-Raymond, M.D.

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  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: Principal Investigator

Model Details: RT 28Gy in 7 fractions with a concomitant boost of 42Gy in 7 fractions+ Temozolomide (75mg/m2) followed by surgery then Temozolomide (150-200mg/m2) q 5 days every 28 days.

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: March 29, 2018
• Study Start: March 1, 2017
• Primary Completion: June 1, 2021
• Study Completion: November 1, 2023
• Last Updated: August 14, 2019

Record last verified: 2019-08

Locations

CA (1)