FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma
Condition: Astrocytoma, Grade II; Astrocytoma, Grade III
MeSH terms: Astrocytoma
Intervention: TTFields with adjuvant temozolomide
Intervention description: 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.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

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.
    

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.