FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma

NCT03906448 | Terminated Phase 2 Results DMC FDA Drug FDA Device

• 2 other identifiers: IRB201800600OCR17711
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 5

Brief Summary

This is a phase 2, multi-institutional, historically-controlled, study of 100 patients with newly diagnosed Grade II and III astrocytoma comparing the combination of TTFields with adjuvant temozolomide versus temozolomide alone in historical controls after the completion of definitive chemoradiotherapy. Study treatment may continue past first tumor recurrence. The primary endpoint will be overall survival.

Conditions

Astrocytoma, Grade II; Astrocytoma, Grade III

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Frequency of overall survival in study participants. 2 years of active treatment, lifelong survival follow-up.

  Up to 2 years

Study Arms (2)

Astrocytoma Patients

EXPERIMENTAL

Patients newly diagnosed with Grade II and III astrocytoma.

Combination Product: TTFields with adjuvant temozolomide

Control Arm

NO INTERVENTION

Data collection from medical record only

Interventions

TTFields with adjuvant temozolomide COMBINATION_PRODUCT

Patients will begin study treatment with temozolomide and TTFields within 2 weeks of the baseline evaluation, and no later than 6 weeks from last dose of concomitant temozolomide or radiation therapy (the latter of the two). A minimum of 6 and a maximum of 12 cycles of adjuvant temozolomide will be given, depending on tolerability and toxicity.

Also known as: Optune

Astrocytoma Patients

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Life expectancy of at least 3 months
• Histologic confirmation of WHO Grade II or III astrocytoma---mixed oligoastrocytomas are permitted
• p/19q intact per FISH and/or ATRX mutation(s) per immunohistochemistry or next-generation sequencing (e.g. Foundation Medicine, TEMPUS, Caris, or similar CLIA-certified sequencing service)
• Mutational identity determined by CLIA-certified sequencing including:
• IDH1/2 wildtype (i.e. lack of detectable mutations on the sequencing report) and
• TERT promoter mutation
• Karnofsky performance status ≥70%
• Maximal safe resection---biopsy alone is allowed
• Completed standard chemoradiation with total RT dose of at least 40 Gy and concurrent temozolomide (75mg/m2 daily dose with 80% prescribed dose completed)
• Patients with a tumor that was biopsied or resected in the past followed by observation only without definitive chemoradiation and/or chemotherapy given will be eligible, as long as: repeat maximal surgical resection (biopsy only allowed) has been performed, definitive temozolomide/RT treatment meets the criteria above, and adjuvant temozolomide treatment is planned
• Candidate for adjuvant high dose temozolomide per investigator's clinical judgement
• Adjuvant Temozolomide start date at least 4 weeks, but not more than 6 weeks, from the later of last dose of concomitant temozolomide or radiotherapy
• No evidence of early disease progression per RANO criteria at the time of enrollment

You may not qualify if:

• Prior treatment with anti-angiogenic agents including bevacizumab.
• Prior treatment with TTFields.
• Progressive disease (according to RANO criteria) after temozolomide/RT.
• Actively participating in another clinical treatment trial intended to treat the underlying astrocytoma.
• Females who are pregnant or breastfeeding.
• Significant co-morbidities at baseline (within 2 weeks prior to adjuvant temozolomide start) which would prevent adjuvant temozolomide treatment:
• Thrombocytopenia (platelet count \< 100 x 103/μL)
• Neutropenia (absolute neutrophil count \< 1.5 x 103/μL)
• CTC grade 4 non-hematological toxicity (except for alopecia, nausea, vomiting)
• Significant liver function impairment - AST or ALT \> 5 times the upper limit of normal
• Total bilirubin \> 2 times upper limit of normal
• Significant renal impairment (GFR ≤ 30 ml/min)
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• A skull defect such as missing bone with no replacement
• Bullet fragments embedded the skull

Sponsors & Collaborators

• University of Florida: lead
• NovoCure Ltd.: collaborator

Study Sites (5)

UF Health at the University of Florida

Gainesville, Florida, 32610, United States

Location

USF Health Morsani College of Medicine-Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Brown University-Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Astrocytoma

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

This multicenter center study was terminated early by mutual decision between the Study Chair/IDE Sponsor and Novocure; therefore, statistical analysis of the 1 participant in the intervention arm was not done.

Results Point of Contact

• Title: David Tran, MD, PhD
• Organization: University of Florida

david.tran@neurosurgery.ufl.edu

352-273-9000

Study Officials

• David Tran, MD, PhD

  University of Florida

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 8, 2019
• Study Start: May 20, 2019
• Primary Completion: June 8, 2020
• Study Completion: June 8, 2020
• Last Updated: September 23, 2021
• Results First Posted: September 23, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)