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

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ClinicalTrials.gov Identifier: NCT03906448
Recruitment Status : Terminated (The study was terminated because the Study Chair/IDE Sponsor and Novocure determined that conducting this trial was not feasible without CMS approval.)
First Posted : April 8, 2019
Last Update Posted : June 17, 2020
Sponsor:
Collaborator:
NovoCure Ltd.
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE April 4, 2019
First Posted Date  ICMJE April 8, 2019
Last Update Posted Date June 17, 2020
Actual Study Start Date  ICMJE May 20, 2019
Actual Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2019)
Overall Survival [ Time Frame: Up to 2 years ]
Frequency of overall survival in study participants. 2 years of active treatment, lifelong survival follow-up.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma
Official Title  ICMJE 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)
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.
Detailed Description

Patients with newly diagnosed high-risk Grade II or III 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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Astrocytoma, Grade II
  • Astrocytoma, Grade III
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Astrocytoma Patients
    Patients newly diagnosed with Grade II and III astrocytoma.
    Intervention: Combination Product: TTFields with adjuvant temozolomide
  • No Intervention: Control Arm
    Data collection from medical record only
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 15, 2020)
2
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2019)
100
Actual Study Completion Date  ICMJE June 8, 2020
Actual Primary Completion Date June 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 in the brain stem and/or the cerebellum
  • History of hypersensitivity reaction to temozolomide, Dacarbazine (DTIC) or hydrogel.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03906448
Other Study ID Numbers  ICMJE IRB201800600
OCR17711 ( Other Identifier: UF OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE NovoCure Ltd.
Investigators  ICMJE
Study Chair: David Tran, MD, PhD University of Florida
PRS Account University of Florida
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP