Astrocytoma, Grade IIPhase 2FORWARDNCT03906448
FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma
A Phase 2 study testing TTFields with adjuvant temozolomide in people with Astrocytoma, Grade II and Astrocytoma, Grade III, run by University of Florida at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Astrocytoma, Grade II, Astrocytoma, Grade III
- What is being tested?
- TTFields with adjuvant temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 5 sitesUnited States
- Study dates
- 20 May 2019to 8 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
- 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.
- 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.
- Refer to section 10.2.1 for guidance on highly effective contraceptive methods acceptable in this study.
- 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.
Who cannot join
- 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:
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- 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
- Tumors located in the brain stem and/or the cerebellum
- History of hypersensitivity reaction to temozolomide, Dacarbazine (DTIC) or hydrogel.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Henry Ford Health System
Detroit, Michigan, 48202
UF Health at the University of Florida
Gainesville, Florida, 32610
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
Brown University-Rhode Island Hospital
Providence, Rhode Island, 02903
USF Health Morsani College of Medicine-Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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)
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.
Read the 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).
- Conditions
- Astrocytoma, Grade II, Astrocytoma, Grade III
- Being tested
- TTFields with adjuvant temozolomide
- Medical subject headings
- Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTFields with adjuvant temozolomideCombination product
Also called Optune
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.
| Study group | Role | What they receive |
|---|---|---|
| Astrocytoma Patients | Experimental | Patients newly diagnosed with Grade II and III astrocytoma. Receives: Combination Product: TTFields with adjuvant temozolomide |
| Control Arm | No intervention | Data collection from medical record only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Frequency of overall survival in study participants. 2 years of active treatment, lifelong survival follow-up.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start20 May 2019
- Primary completion8 Jun 2020
- Study completion8 Jun 2020
Why it stopped: The study was terminated because the Study Chair/IDE Sponsor and Novocure determined that conducting this trial was not feasible without CMS approval.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Astrocytoma, Grade IIStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- NovoCure Ltd.
- Responsible party
- Sponsor
- Investigators
- David Tran, MD, PhD, Study chair, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03906448
- Sponsor's protocol ID
- IRB201800600
- Other IDs
- OCR17711
- Acronym
- FORWARD
- Status last verified
- Aug 2021
- First submitted
- 4 Apr 2019
- Last updated
- 23 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03906448
- Acronym / sponsor ID
- FORWARD / IRB201800600
- Conditions
- Astrocytoma, Grade II, Astrocytoma, Grade III
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated because the Study Chair/IDE Sponsor and Novocure determined that conducting this trial was not feasible without CMS approval.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- NovoCure Ltd.
- Study start
- 20 May 2019 (actual)
- Primary completion
- 8 Jun 2020 (actual)
- Study completion
- 8 Jun 2020 (actual)
- First posted
- 8 Apr 2019 (actual)
- Results
- Posted 23 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Astrocytoma Patients | Experimental | Combination Product: TTFields with adjuvant temozolomidePatients newly diagnosed with Grade II and III astrocytoma. |
| Control Arm | No intervention | –Data collection from medical record only |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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)
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TTFields with adjuvant temozolomideAlso: OptunePatients 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. | Combination product | Astrocytoma Patients |
Primary outcome
Overall Survival
Time frame: Up to 2 years
Frequency of overall survival in study participants. 2 years of active treatment, lifelong survival follow-up.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Tran, MD, PhD study chair
University of Florida
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TTFields with adjuvant temozolomide in people with Astrocytoma, Grade II and Astrocytoma, Grade III, run by University of Florida at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2021.