A Phase 2, Single Arm, Multi-center, Open-Label Trial to Evaluate the Safety and Efficacy of Treatment with Tumor Treating Fields (TTFields) and Chemotherapy As First-Line Treatment for Subjects with Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Gastric (GC) Adenocarcinoma
Overview
- Phase
- Not Applicable
- Intervention
- NovoTTF-100L(P)
- Conditions
- Gastric Cancer
- Sponsor
- NovoCure Ltd.
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Objective response rate
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The study is a prospective, single arm, phase II trial aimed to evaluate the efficacy and safety of Tumor Treating Fields (TTFields) concomitant with XELOX for the treatment of unresectable, locally advanced or metastatic Gastroesophageal Junction (GEJ) or Gastric (GC) Adenocarcinoma who were previously untreated with systemic therapy. 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 (TTFields, TTF) has demonstrated significant activity in in vitro gastric cancer pre-clinical models both as a single modality treatment and in combination with chemotherapies. In addition, TTFields have shown to inhibit metastatic spread of malignant melanoma in in vivo experiment. Prospective, multi-center clinical studies of TTFields have shown the safety of the treatment when administered to the abdomen for pancreatic cancer and ovarian cancer. In addition, a phase III trial of Optune® (200 kHz) as monotherapy compared to active chemotherapy in recurrent glioblastoma patients showed TTFields to be equivalent to active chemotherapy in extending survival, associated with minimal toxicity, good quality of life, and activity within the brain (14% response rate). Finally, a phase III trial of Optune® combined with maintenance temozolomide compared to maintenance temozolomide alone has shown that combined therapy led to a significant improvement in both progression free survival and overall survival in patients with newly diagnosed glioblastoma without the addition of high grade toxicity and without decline in quality of life. DESCRIPTION OF THE TRIAL: All patients included in this trial are patients with unresectable Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma. In addition, all patients must meet all eligibility criteria. All eligible patients will receive continuous Tumor Treating Fields (TTFields) - NovoTTF-100L (P) treatment at 150 KHz frequency, and XELOX regimen (combination of oxaliplatin + capecitabine). Patients will be assessed once every 9 weeks according to RECIST v1.1. Study treatment should be continued until disease progression, intolerable toxicity or withdrawal of informed consent.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing to and be able to sign an informed consent form
- •Male or female aged ≥ 18 years
- •Be able to receive the treatment in compliance with the study protocol in the discretion of the investigator
- •ECOG Performance status score 0 or 1
- •Histologically confirmed unresectable, locally advanced or metastatic Gastroesophageal Junction (GEJ) or Gastric (GC) Adenocarcinoma. The subject must be previously untreated with systemic treatment (including chemotherapy, targeted therapy, and Onco-Immunotherapy), and without resection of primary gastric focus.
- •Subjects must have at least one measurable lesion as per RECIST 1.1 criteria; and the tumor assessment baseline should be performed and established by the investigator within 28 days prior to study treatment.
- •Life expectancy ≥ 3 months
- •The allowed previous treatment: Palliative radiotherapy for bone metastasis is allowed if it has been completed within 2 weeks prior to the study treatment and all treatment-related toxicity should be recovered to Grade 1 before enrollment, according to CTCAE 5.
- •Women of childbearing potential must have a negative serum pregnancy test result during screening. Post-menopausal women and surgically sterilized women are not required to undergo a pregnancy test. Females of childbearing potential/males and its partners who are sexually active must agree to adopt methods of contraception from signing the ICFs to within at least 6 months after the last dose of study drug. Besides, male subjects must be willing to refrain from sperm donation during this time.
- •Able to operate the NovoTTF-100L (P) System independently or with the help of a caregiver.
Exclusion Criteria
- •White blood cell count (WBC) \< 2 × 10\^9 / L
- •Absolute neutrophil count (ANC) \< 1.5 × 10\^9 / L
- •Platelet count \< 100 × 10\^9 / L
- •Hemoglobin \< 90 g/L
- •Serum albumin \< 30 g/L
- •Serum creatinine \> 1.5 × ULN, or creatinine clearance\< 60 mL/min/1.73 m\^2 calculated by Cockcroft-Gault
- •Serum total bilirubin \> 1.5 × ULN
- •AST, ALT, ALP:
- •Patients without liver metastasis or bone metastases i. AST or ALT \>1.5 × ULN and ALP \> 2.5 × ULN ii. AST or ALT \>2.5 × ULN
- •Patients with liver metastasis and without bone metastases i. AST or ALT \> 5 × ULN and ALP \> 2.5 × ULN
Arms & Interventions
NovoTTF-100L(P)
Patients receive TTFields using the NovoTTF-100L(P) System together with XELOX. For HER-2 positive patients, Trastuzumab is given together with XELOX.
Intervention: NovoTTF-100L(P)
NovoTTF-100L(P)
Patients receive TTFields using the NovoTTF-100L(P) System together with XELOX. For HER-2 positive patients, Trastuzumab is given together with XELOX.
Intervention: Oxaliplatin
NovoTTF-100L(P)
Patients receive TTFields using the NovoTTF-100L(P) System together with XELOX. For HER-2 positive patients, Trastuzumab is given together with XELOX.
Intervention: Capecitabine
NovoTTF-100L(P)
Patients receive TTFields using the NovoTTF-100L(P) System together with XELOX. For HER-2 positive patients, Trastuzumab is given together with XELOX.
Intervention: Trastuzumab
Outcomes
Primary Outcomes
Objective response rate
Time Frame: 2 years
Investigator-assessed objective response rate (ORR) as per RECIST v1.1
Secondary Outcomes
- Disease control rate(2 years)
- Time to progression(2 years)
- Duration of response(2 years)
- Overall survival(2 years)
- Progression-free survival(2 years)
- Severity and frequency of adverse events(2 years)
- 12 month overall survival rate(2 years)