Safety and Efficacy of TTFields (150 kHz) Concomitant With Pemetrexed and Cisplatin or Carboplatin in Malignant Pleural Mesothelioma (STELLAR)

NCT02397928 | Completed Phase 2

• 1 other identifier: EF-23
• Study Type: interventional
• Target: 82
• Locations: 7 countries
• Sites: 13

Brief Summary

The study is a prospective, single arm, non-randomized, open label phase II trial, designed to study the safety and efficacy of a medical device, the NovoTTF-100L concomitant with Pemetrexed and cisplatin or carboplatin in Malignant Pleural Mesothelioma patients. 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.

Conditions

Malignant Pleural Mesothelioma

Keywords

Malignant Pleural Mesothelioma; Treatment; Minimal toxicity; TTFields; Tumor Treating Fields; Novocure; Pemetrexed; Carboplatin; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  1 year

Secondary Outcomes (3)

• Progression Free Survival

  1 year

• Response Rate

  1 year

• Toxicity- incidence of adverse events

  1 year

Study Arms (1)

TTFields concomitant to pemetrexed plus cisplatin/carboplatin

EXPERIMENTAL

Patients will be treated continuously with TTFields, in addition to pemetrexed plus cisplatin/carboplatin

Device: NovoTTF-100L device; Drug: Pemetrexed; Drug: Cisplatin or Carboplatin

Interventions

NovoTTF-100L device DEVICE

Patients will be treated continuously with the NovoTTF-100L device. NovoTTF-100L treatment will consist of wearing four electrically insulated electrode arrays on the thorax. The treatment enables the patient to maintain regular daily routine.

Also known as: TTFields

TTFields concomitant to pemetrexed plus cisplatin/carboplatin

Pemetrexed DRUG

Pemetrexed 500 mg/m2 will be administered by intravenous infusion over 10 minutes or according to institutional administration timing on day 1 of a 21-day cycle.

TTFields concomitant to pemetrexed plus cisplatin/carboplatin

Cisplatin or Carboplatin DRUG

Cisplatin 75 mg/m2 or carboplatin AUC 5 will be administered by infusion after adequate hydration according to institutional practices beginning approximately 30 minutes after the end on the pemetrexed infusion on day 1 of a 21-day cycle.

TTFields concomitant to pemetrexed plus cisplatin/carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathological or histological evidence of mesothelioma
• ≥ 18 years of age
• Not candidate for curative treatment (surgery or radiotherapy)
• At least 4 weeks since major surgery
• At least one measurable or evaluable lesion according to modified RECIST Criteria
• ECOG Performance Status of 0-1
• Life expectancy of at least 3 months
• Participants of childbearing age must use effective contraception as indicated by the investigator
• All subjects must sign written informed consent.
• Able to operate the NovoTTF-100L System independently or with the help of a caregiver

You may not qualify if:

• Patient candidate for surgery or radiotherapy with curative intent
• Previous chemotherapy or radiation
• Prior malignancy requiring anti-tumor treatment (apart from in-situ cervical cancer, in situ breast cancer, non-melanomatous skin cancers, or any malignancy for which treatment was received and there is no evidence of disease for at least 5 years) or concurrent malignancy
• Significant co-morbidities within 4 weeks prior to enrollment, resulting in the following laboratory findings:
• Significant liver function impairment:
• AST or ALT \> 3 times the upper limit of normal
• Total bilirubin ≥ 1.5 times upper limit of normal
• Significant renal impairment (serum creatinine \> 1.7 mg/dL)
• Coagulopathy (as evidenced by PT or APTT \>1.5 times control in subjects not undergoing anticoagulation)
• Thrombocytopenia (platelet count \< 100 x 10\^3/μL)
• Neutropenia (absolute neutrophil count \< 1.5 x 10\^3/μL)
• Anemia (Hb \< 10 g/dL)
• Severe acute infection
• Significant comorbidity which is expected to affect patient's prognosis or ability to receive the combined therapy:
• History of significant cardiovascular disease unless the disease is well controlled.

Sponsors & Collaborators

• NovoCure Ltd.: lead

Study Sites (13)

Antwerp University Hospital, Thoracic Oncology

Antwerp, Belgium

Location

Goustave Roussy - Cancer Campus Grand Paris

Villejuif, France

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

A.S.O. "SS Antonio e Biagio e Cesare Arrigo"

Alessandria, Italy

Location

Cliniche Humanitas Gavazzeni

Bergamo, Italy

Location

Ospedale Villa Scassi

Genoa, Italy

Location

Ospedaliera di Perugia

Perugia, Italy

Location

Ospedaliero Universitaria Pisana

Pisa, Italy

Location

Erasmus Mc

Rotterdam, Netherlands

Location

Medical University Gdansk

Gdansk, Poland

Location

Katedra i Klinika Onkologii Uniwersytetu Medycznegi im. Karola Marcinkowskiego w Poznaniu

Poznan, Poland

Location

Klinika Nowotworów Pluca I Klatki Piersiowej

Warsaw, Poland

Location

Vall d' Hebron Institute of Oncology (VHIO) Hospital Vall d'Hebron

Barcelona, Spain

Location

Related Publications (7)

• Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y. Disruption of cancer cell replication by alternating electric fields. Cancer Res. 2004 May 1;64(9):3288-95. doi: 10.1158/0008-5472.can-04-0083.

  PMID: 15126372 BACKGROUND

• Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y. Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10152-7. doi: 10.1073/pnas.0702916104. Epub 2007 Jun 5.

  PMID: 17551011 BACKGROUND

• Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V, Ram Z, Villano JL, Rainov N, Weinberg U, Schiff D, Kunschner L, Raizer J, Honnorat J, Sloan A, Malkin M, Landolfi JC, Payer F, Mehdorn M, Weil RJ, Pannullo SC, Westphal M, Smrcka M, Chin L, Kostron H, Hofer S, Bruce J, Cosgrove R, Paleologous N, Palti Y, Gutin PH. NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012 Sep;48(14):2192-202. doi: 10.1016/j.ejca.2012.04.011. Epub 2012 May 18.

  PMID: 22608262 BACKGROUND

• Pless M, Droege C, von Moos R, Salzberg M, Betticher D. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer. 2013 Sep;81(3):445-450. doi: 10.1016/j.lungcan.2013.06.025. Epub 2013 Jul 23.

  PMID: 23891283 BACKGROUND

• Pless M, Weinberg U. Tumor treating fields: concept, evidence and future. Expert Opin Investig Drugs. 2011 Aug;20(8):1099-106. doi: 10.1517/13543784.2011.583236. Epub 2011 May 9.

  PMID: 21548832 BACKGROUND

• Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y. Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis. 2009;26(7):633-40. doi: 10.1007/s10585-009-9262-y. Epub 2009 Apr 23.

  PMID: 19387848 BACKGROUND

• Ceresoli GL, Aerts JG, Dziadziuszko R, Ramlau R, Cedres S, van Meerbeeck JP, Mencoboni M, Planchard D, Chella A, Crino L, Krzakowski M, Russel J, Maconi A, Gianoncelli L, Grosso F. Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial. Lancet Oncol. 2019 Dec;20(12):1702-1709. doi: 10.1016/S1470-2045(19)30532-7. Epub 2019 Oct 15.

  PMID: 31628016 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Giovanni Luca Ceresoli, MD

  Cliniche Humanitas Gavazzeni

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: March 25, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: September 25, 2018

Record last verified: 2018-09

Locations

FR (1); BE (1); NL (1); DE (1); ES (1); IT (5); PL (3)