Safety, Feasibility and Effect of TTFields (200 kHz) Concomitant With Weekly Paclitaxel in Recurrent Ovarian Carcinoma (INNOVATE)

September 20, 2016 updated by: NovoCure Ltd.

An Open Label Pilot Study of the NovoTTF-100L(O) System (NovoTTF Therapy) (200 kHz) Concomitant With Weekly Paclitaxel for Recurrent Ovarian Carcinoma

The study is a prospective, single arm, non-randomized, open label pilot trial, designed to study the safety, toxicity, feasibility and preliminary efficacy of a medical device, the NovoTTF-100L(O) concomitant with weekly paclitaxel in recurrent ovarian carcinoma 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

PAST PRE CLINICAL AND CLINICAL EXPERIENCE:

The effect of the electric fields generated by the NovoTTF-100L(O) device (Tumor Treating Fields, TTFields, TTF) has demonstrated significant activity in in vitro and in vivo ovarian carcinoma pre-clinical models both as a single modality treatment and in combination with paclitaxel. TTFields 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 non-small cell lung cancer (NSCLC) who had had tumor progression after at least one line of prior chemotherapy received Pemetrexed together with NovoTTF 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 glioblastoma (GBM). The outcome of subjects treated with NovoTTF Therapy was compared to those treated with an effective best standard of care chemotherapy (including bevacizumab). NovoTTF Therapy subjects had comparable overall survival to subjects receiving the best available chemotherapy in the US today. Similar results showing comparability of NovoTTF Therapy to best standard of care (BSC) chemotherapy were seen in all secondary endpoints. Recurrent GBM patients treated with the NovoTTF Therapy 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 Therapy subjects as a group when compared to subjects receiving effective best standard of care chemotherapy.

DESCRIPTION OF THE TRIAL:

All patients included in this trial are diagnosed with recurrent ovarian carcinoma. In addition, all patients must meet all eligibility criteria.

Eligible patients will be enrolled, baseline tests will be performed and the patients will be treated continuously with the device concomitant with weekly paclitaxel until disease progression.

NovoTTF-100L(O) treatment will consist of wearing four electrically insulated electrode arrays on the torso. Electrode array placement will require shaving of the abdomen/back as necessary before and during the treatment. After an initial short visit to the clinic for training and monitoring, patients will be released to continue treatment at home where they can maintain their regular daily routine.

During the trial, the patient will need to return once every 4 weeks to the clinic where an examination by a physician and a routine laboratory examinations will be done. These routine visits will continue for as long as the patient's disease is not progressing.

During the monthly follow up visits to the clinic patients will be examined physically. Additionally, routine blood tests will be performed. A routine CT scan of the chest and abdomen will be performed at baseline and every 8 weeks thereafter, until disease progression. After this follow up plan, patients will be contacted once per month by telephone to answer basic questions about their health status.

SCIENTIFIC BACKGROUND:

Electric fields exert forces on electric charges similar to the way a magnet exerts forces on metallic particles within a magnetic field. These forces cause movement and rotation of electrically charged biological building blocks, much like the alignment of metallic particles seen along the lines of force radiating outwards from a magnet.

Electric fields can also cause muscles to twitch and if strong enough may heat tissues. TTFields are alternating electric fields of low intensity. This means that they change their direction repetitively many times a second. Since they change direction very rapidly (200 thousand times a second), they do not cause muscles to twitch, nor do they have any effects on other electrically activated tissues in the body (brain, nerves and heart). Since the intensities of TTFields in the body are very low, they do not cause heating.

The breakthrough finding made by Novocure was that finely tuned alternating fields of very low intensity, now termed TTFields (Tumor Treating Fields), cause a significant slowing in the growth of cancer cells. Due to the unique geometric shape of cancer cells when they are multiplying, TTFields cause the building blocks of these cells to move and pile up in such a way that the cells physically explode. In addition, cancer cells also contain miniature building blocks which act as tiny motors in moving essential parts of the cells from place to place. TTFields cause these tiny motors to fall apart since they have a special type of electric charge.

As a result of these two effects, cancer tumor growth is slowed and can even reverse after continuous exposure to TTFields.

Other cells in the body (normal healthy tissues) are affected much less than cancer cells since they multiply at a much slower rate if at all. In addition TTFields can be directed to a certain part of the body, leaving sensitive areas out of their reach.

In conclusion, TTField hold the promise of serving as a brand new cancer treatment with very few side effects and promising affectivity in slowing or reversing this disease.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
  • Germany
      • Berlin, Germany
        • Charité - Universitätsmedizin Berlin
  • Spain
      • Madrid, Spain
        • Hospitale Universitario 12 de Octubre
  • Switzerland
      • Bellinzona, Switzerland
        • Ospedale San Giovanni
      • Chur, Switzerland
        • Kantonsspital Graubünden

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma
  2. Recurrent ovarian cancer with any number of prior therapies
  3. 18 years of age and older
  4. Life expectancy of at least 12 weeks
  5. Measurable disease according to the revised RECIST criteria version 1.1. A lesion in a previously irradiated field is considered "non-measurable" and cannot be a "target lesion".
  6. ECOG score 0-1 (see Appendix A)

  7. Adequate bone marrow, liver and renal functions:

    1. Absolute neutrophil count ≥ 1.5 x 10 9/L
    2. Platelet count ≥ 100 x 10 9/L
    3. Hemoglobin ≥ 10 g/dL
    4. AST and/or ALT ≤ 3 x upper limit of normal range (ULN) or ≤ 5 x ULN if patient has documented liver metastases
    5. Bilirubin ≤1.5 x ULN
    6. Serum creatinine ≤ 1.5 x ULN
    7. Coagulation status: PT and PTT within normal limits or within therapeutic limits for patients receiving anticoagulation.
  8. Able to operate the NovoTTF-100L(O) System independently or with the help of a caregiver
  9. No concurrent anti-tumor therapy (beyond weekly paclitaxel and NovoTTF Therapy as per protocol)
  10. At least 4 weeks since major surgery

Exclusion Criteria:

  1. Meningeal carcinomatosis or known brain metastases which have not been treated, require steroid treatment, or are symptomatic.
  2. Any other malignancy requiring anti-tumor treatment in the past three years, except resected non-melanomatous skin cancer, breast carcinoma in situ, adequately treated stage I breast cancer or in situ cervical cancer.
  3. Chemotherapy within 4 weeks prior to treatment start.
  4. Radiotherapy within 4 weeks prior to treatment start.

  5. Significant comorbidity which is expected to affect patient's prognosis or ability to receive the combined therapy:

    1. 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).
    2. History of arrhythmia that is symptomatic or requires treatment. Patients with stable atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial.
    3. Active infection or any serious underlying medical condition that would impair the ability of the patient to receive protocol therapy.
    4. 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.
  6. Implantable electronic medical devices including pacemaker, implantable automatic defibrillator, etc.
  7. Known history of sensitivity to taxanes or drugs containing Cremophor
  8. Grade 2 or greater peripheral neuropathy
  9. Known allergies to medical adhesives or hydrogel
  10. Pregnant or breast feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TTFields in combination with weekly paclitaxel
Patients will be treated continuously with the NovoTTF-100L(O) device, in addition to weekly paclitaxel.
Device: NovoTTF-100L(O)
Patients will be treated continuously with the NovoTTF-100L(O). NovoTTF-100L(O) treatment will consist of wearing four electrically insulated electrode arrays on the torso. The treatment enables the patient to maintain regular daily routine.
Drug: Paclitaxel
Paclitaxel 80 mg/m2 over 1 hour infusion will be administered weekly for 8 weeks and then on days 1, 8, 15 of each subsequent 28 day cycle.
Other Names:
  • Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Adverse Events Severity and Frequency
Time Frame: 1.5 years
1.5 years
Number of patients prematurely discontinuing TTFields due to Skin Toxicity
Time Frame: 1.5 yeras
1.5 yeras

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 1.5 years
1.5 years
Overall Survival
Time Frame: 1.5 years
1.5 years
1 Year Survival Rate
Time Frame: 1.5 years
1.5 years
Overall Radiological Response Rate and Duration of Response
Time Frame: 1.5 years
1.5 years
CA-125 Response Rate and Duration of Response
Time Frame: 1.5 years
1.5 years
Patients' compliance with TTFields Therapy
Time Frame: 1.5 years
Patient compliance will be assessed by evaluating the device log file which will be downloaded every 4 weeks from the NovoTTF-100L(O) System. Compliance will be presented as an hourly average over a 24 hour period during the 4 weeks and as an average percentage of use over the 4 week period.
1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NovoCure Ltd.

Investigators

  • Principal Investigator: Cristina Sessa, MD, Ospedale San Giovanni

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

September 15, 2014

First Submitted That Met QC Criteria

September 16, 2014

First Posted (Estimate)

September 19, 2014

Study Record Updates

Last Update Posted (Estimate)

September 21, 2016

Last Update Submitted That Met QC Criteria

September 20, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EF-22

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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