Tamoxifen Versus Etoposide After First Recurrence in GBM Patients

A Randomized Controlled Trial of Tamoxifen Versus Etoposide for Patients With First Recurrence of Glioblastoma Multiforme

The investigator propose a single-center randomized phase II controlled study designed to compare the management of first recurrence of GBM using etoposide versus tamoxifen.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: Etoposide; Drug: Tamoxifen

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jacob Easaw, MD, PhD, FRCPC; Phone Number: 780-432-8290; Email: jay.easaw@ahs.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Recruiting
      • Cross Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically proven GBM with progression after previous first line chemoradiotherapy with temozolomide.
2. Progression documented by MRI with at least one bi-dimensionally measurable target lesion with one diameter of at least 10 mm, visible on two or more axial slices 5 mm apart.
3. Not received radiotherapy within the three months before the diagnosis of progression.
4. Stable or decreasing dose of corticosteroids prior to randomization: corticosteroids (dexamethasone) should be given at the lowest dose needed to control symptoms arising from increased intracerebral edema.
5. ECOG performance 0-2 (Appendix 2).
6. Age from 18-65 years.
7. Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 72 hours prior to the first dose of study treatment. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.

8. Patients of childbearing / reproductive potential should use adequate birth control methods, as defined by the investigator, during the study treatment period and for a period of 60 days after the last dose of study drug. A highly effective method of birth control is defined as those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

   Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.

9. Laboratory evaluation obtained within 7 days prior to randomization, with adequate function as defined below:

   • ANC ≥ 1.5 x 109/L
   • Platelets ≥ 100 x 109/L
   • Serum creatinine ≤ 1.5 times ULN
   • Total serum bilirubin ≤ 1.5 times ULN
   • ALT < 3 times ULN
   • AST < 3 times ULN
   • Alkaline phosphatase < 3 times ULN
10. Patient must understand and sign an informed consent prior to study registration.

Exclusion Criteria:

1. History of another malignancy or a concurrent malignancy (exceptions include patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ.
2. Uncontrolled hypertension (systolic blood pressure >150 mm Hg or diastolic blood pressure >100 mm Hg).
3. Any arterial or venous thrombosis up to 6 months before registration.
4. Evidence of recent hemorrhage on brain MRI.
5. Substantial cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (> New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Etoposide	Drug: Etoposide; etoposide 50mg/m2 daily
EXPERIMENTAL: Tamoxifen	Drug: Tamoxifen; Tamoxifen 20 mg daily for 3 days then 20 mg BID for 3 days then increase by 20 mg daily every 3 days until 100 mg BID continuously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 month progression-free survival	Time between randomization and radiographic or clinical progression leading to change in therapy for recurrent disease or death due to any cause.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year progression-free survival	Time between randomization and radiographic or clinical progression leading to change in therapy for recurrent disease or death due to any cause.	12 months
Overall survival	Time between randomization and death due to any cause. Patients without an event will be censored the last time they were known to be alive.	Median, 6-month, 1-year, and 2-year OS rates will be measured
Health-related quality-of-life status	Health-related quality-of-life will be assessed using the EORTC QLQ-BN20 brain tumor module questionnaire. This is a self-report questionnaire consisting of 20 items that assess future uncertainty, visual disorder, motor dysfunction, and communication deficit in brain tumor patients	Throughout study completion, up to 5 years.
Adverse events	This includes fatigue, hematologic toxicities (neutropenia, thrombocytopenia, leukopenia, anemia), liver toxicities, hypertension, diarrhea, seizures and thrombosis and will all be recorded.	Throughout the whole duration of the trial, up to 5 years

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 28, 2022
• Primary Completion (ANTICIPATED): August 1, 2026
• Study Completion (ANTICIPATED): December 1, 2026

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (ACTUAL): February 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Etoposide; Tamoxifen
• Other Study ID Numbers: IIT-0014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No