Clinical Trials /

FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma

NCT03906448

Description:

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.

Related Conditions:
  • Astrocytoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: IRB201800600
  • SECONDARY ID: OCR17711
  • NCT ID: NCT03906448

Conditions

  • Astrocytoma, Grade II
  • Astrocytoma, Grade III

Purpose

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 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).
    

Trial Arms

NameTypeDescriptionInterventions
Astrocytoma PatientsExperimentalPatients newly diagnosed with Grade II and III astrocytoma.
    Control ArmNo InterventionData collection from medical record only

      Eligibility 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 in the brain stem and/or the cerebellum
      
                -  History of hypersensitivity reaction to temozolomide, Dacarbazine (DTIC) or hydrogel.
            
      Maximum Eligible Age:99 Years
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Overall Survival
      Time Frame:Up to 2 years
      Safety Issue:
      Description:Frequency of overall survival in study participants. 2 years of active treatment, lifelong survival follow-up.

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:University of Florida

      Last Updated

      February 25, 2020