A Phase II Randomized Study of TTField Therapy (150 kHz) Versus Supportive Care in Non-small Cell Lung Cancer Patients With 1-5 Brain Metastases Following Optimal Standard Local Treatment
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- NovoCure Ltd.
- Enrollment
- 18
- Locations
- 7
- Primary Endpoint
- Time to Local and Distant Progression in The Brain
Study Overview
Brief Summary
The study is a prospective, randomly controlled phase II trial, designed to test the efficacy, safety and neurocognitive outcomes of a medical device, the NovoTTF-100A, in the treatment of NSCLC patients with controlled systemic disease, following optimal standard local treatment for 1-5 brain metastases (BM). The device is an experimental, portable, battery operated device for chronic administration of alternating electric fields (termed TTFields or TTF) to the region of the malignant tumor, by means of surface, insulated electrode arrays.
Detailed Description
PAST PRE CLINICAL AND CLINICAL EXPERIENCE:
The effect of the electric fields generated by the NovoTTF-100A device (TTFields, TTF) has demonstrated significant activity in in vitro and in vivo NSCLC pre-clinical models both as a single modality treatment and in combination with chemotherapies. TTField therapy has also shown to inhibit metastatic spread of malignant melanoma in in vivo experiment.
In a small scale pilot study, patients with stage IIIB- IV NSCLC who had had tumor progression after at least one line of prior chemotherapy received Pemetrexed together with TTField therapy applied to the chest and upper abdomen until disease progression. Efficacy endpoints were remarkably high compared to historical data for Pemetrexed alone.
In a large prospective, randomized trial, in recurrent GBM. The outcome of subjects treated with the NovoTTF-100A device was compared to those treated with an effective best standard of care chemotherapy (including bevacizumab). NovoTTF-100A subjects had comparable overall survival to subjects receiving the best available chemotherapy in the US today. Similar results showing comparability of NovoTTF-100A to BSC chemotherapy were seen in all secondary endpoints. Recurrent GBM patients treated with the NovoTTF-100A device in this trial experienced fewer side effects in general, significantly fewer treatment related side effects, and significantly lower gastrointestinal, hematological and infectious adverse events compared to controls. The only device-related adverse events seen were a mild to moderate skin irritation beneath the device electrodes. Finally, quality of life measures were better in NovoTTF-100A subjects as a group when compared to subjects receiving effective best standard of care chemotherapy.
DESCRIPTION OF THE TRIAL:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18 years of age and older
- •Life expectancy of ≥ 3 months
- •Performance status WHO 0-2 (may be assessed under steroid therapy)
- •New diagnosis of BM from a histologically or cytologically confirmed primary or metastatic NSCLC tumor, meeting 1 of the following criteria:
- •Stable systemic cancer for the last 3 months (achieved by surgery, radiotherapy, or chemotherapy), defined as absence of symptomatic and radiological progression, according to RECIST Criteria
- •Asymptomatic synchronous primary tumor (treatable by surgery, radiotherapy, or chemotherapy)
- •BM biopsy required if no extracranial tumor (unknown primary tumor) OR extracranial diagnosis made more than 4 years previously
- •Must have one to five brain lesions, confirmed by contrast enhanced MRI, all amenable either surgical resection, or to SRS according to the following criteria:
- •Largest diameter ≤ 3.5 cm for single metastasis
- •Largest diameter ≤ 2.5 cm for 2 to 5 metastases
- •Stable or decreasing dose of steroids for at least 5 days before screening
- •Patients must be receiving optimal therapy for their extracranial disease according to local practice at each center. Patients may continue on systemic therapy while receiving TTField therapy
Exclusion Criteria
- •Infratentorial metastases
- •Leptomeningeal metastases
- •Patients who previously received WBRT or SRS for BM (prior resection is allowed as long as any remaining tumor is treated under the protocol)
- •Significant co-morbidity which is expected to affect patient's prognosis or ability to receive optimal systemic therapy:
- •Inadequate and clinically relevant hematological, hepatic and renal abnormalities defined as: Neutrophil count > 1.5 x 10 9/L and platelet count > 100 x 10 9/L; bilirubin < 1.5 x ULN; AST and/or ALT < 2.5 x ULN or < 5 x ULN is patient has documented liver metastases; and serum creatinine < 1.5 x ULN
- •History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
- •History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial
- •History of cerebrovascular accident (CVA) within 6 months prior to randomization
- •Active infection or serious underlying medical condition that would impair the ability of the patient to received protocol therapy
- •History of any psychiatric condition that might impair the patient's ability to understand or comply with the requirements of the study or to provide consent
- •Pregnant, or women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception
- •Unable to operate the NovoTTF-100A device independently or with the help of a caregiver
- •Implantable electronic medical devices in the brain
- •Known allergies to medical adhesives or hydrogel
- •Concurrent brain directed therapy (beyond SRS, surgery and TTField therapy as per protocol)
Outcomes
Primary Outcomes
Time to Local and Distant Progression in The Brain
Time Frame: 2 years
Secondary Outcomes
- Overall Survival(2 years)
- 6-Month Disease Control Rate in The Brain(2 years)
- Neurocognitive Function (MMSE and HVLT)(2 years)
- Quality of life (QLQ-C30 and BN-20)(2 years)
- Overall (systemic) Progression-Free Survival (RECIST Criteria)(2 years)
- Adverse Events Severity and Frequency(2 years)