Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma (FORWARD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03906448
Recruitment Status : Recruiting
First Posted : April 8, 2019
Last Update Posted : November 15, 2019
Sponsor:
Information provided by (Responsible Party):
University of Florida

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.

Condition or disease Intervention/treatment Phase
Astrocytoma, Grade II Astrocytoma, Grade III Combination Product: TTFields with adjuvant temozolomide Phase 2

Detailed Description:

Patients with newly diagnosed high-risk Grade II or II astrocytoma must undergo maximal safe resection (biopsy alone may be eligible) and chemoradiotherapy: concomitant 75mg/m2 daily temozolomide with 80% prescribed dose completed and RT with minimal RT dose of 40 Gy delivered.

Within three weeks prior to beginning adjuvant temozolomide, all patients will undergo a Baseline contrast-enhanced MRI of the brain. Within two weeks prior to beginning adjuvant temozolomide, all patients will undergo baseline assessments. 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. Patients will be seen and examined before each cycle of temozolomide. After a maximum of 12 cycles of adjuvant temozolomide, patients will be seen every 8 weeks. Brain MRI and QoL assessments will be performed every 8 weeks following the baseline MRI for the first 2 years then every 3 months thereafter until second progression (when TTFields treatment will be terminated).


Layout table for study information
Study Type : Interventional
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Historically Controlled Study Testing the Efficacy of TTFields (Optune®) With Adjuvant Temozolomide in High Risk WHO Grade II and III Astrocytomas (FORWARD)
Actual Study Start Date : May 20, 2019
Estimated Primary Completion Date : April 30, 2022
Estimated Study Completion Date : April 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Astrocytoma Patients
Patients newly diagnosed with Grade II and III astrocytoma.
Combination Product: TTFields with adjuvant temozolomide
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.
Other Name: Optune




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Up to 2 years ]
    Frequency of overall survival in study participants. 2 years of active treatment, lifelong survival follow-up.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 1p/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:

    1. IDH1/2 wildtype (i.e. lack of detectable mutations on the sequencing report) and
    2. 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
  • Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy.

    1. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
    2. Refer to section 10.2.1 for guidance on highly effective contraceptive methods acceptable in this study.
    3. WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as: Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
  • Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

Exclusion Criteria:

  • 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:

    1. Thrombocytopenia (platelet count < 100 x 103/μL)
    2. Neutropenia (absolute neutrophil count < 1.5 x 103/μL)
    3. CTC grade 4 non-hematological toxicity (except for alopecia, nausea, vomiting)
    4. Significant liver function impairment - AST or ALT > 5 times the upper limit of normal
    5. Total bilirubin > 2 times upper limit of normal
    6. 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
  • Tumors located entirely in the infra-tentorial location.
  • History of hypersensitivity reaction to temozolomide, Dacarbazine (DTIC) or hydrogel.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03906448


Contacts
Layout table for location contacts
Contact: Annie Allen 352-294-8836 forward-study@ufl.edu

Locations
Layout table for location information
United States, Florida
UF Health at the University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Annie Allen    352-294-8836    forward-study@ufl.edu   
Principal Investigator: Ashley Ghiaseddin, MD         
United States, Michigan
Henry Ford Health System Recruiting
Detroit, Michigan, United States, 48202
Contact: Ken Winters, R.N., OCN    313-916-1049    kwinter1@hfhs.org   
Principal Investigator: James Snyder, D.O.         
Sponsors and Collaborators
University of Florida
Investigators
Layout table for investigator information
Study Chair: David Tran, MD, PhD University of Florida

Layout table for additonal information
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT03906448     History of Changes
Other Study ID Numbers: IRB201800600
OCR17711 ( Other Identifier: UF OnCore )
First Posted: April 8, 2019    Key Record Dates
Last Update Posted: November 15, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents