Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of the NovoTTF-100L System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03203525
Recruitment Status : Not yet recruiting
First Posted : June 29, 2017
Last Update Posted : January 9, 2019
Sponsor:
Collaborator:
NovoCure Ltd.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of 2 study drug combinations that can be given with the NovoTTF-100L system at 150kHz. The NovoTTF-100L System is a portable device that uses electrical fields intended to stop the growth of tumor cells.

The first study drug combination is modified FOLFOX6 (folic acid, leucovorin, fluorouracil, and oxaliplatin) mFOLFOX6 and bevacizumab. mFOLFOX6 plus bevacizumab is a standard of care option for colorectal cancer that has spread. Patients receiving this combination will also receive treatment with NovoTTF-100L System. It is considered investigational to use mFOLFOX6 and bevacizumab in combination with NovoTTF-100L System. You may experience a delay or will not be able to receive the standard therapy due to potential side effects from the investigational part of the regimen.

The second study drug combination is liposomal doxorubicin, bevacizumab, and temsirolimus. Patients receiving this combinations will also receive treatment with the NovoTTF-100L system.

The safety of these combinations will also be studied. The study doctor can explain how the study drugs are designed to work.

This is an investigational study. The combination of mFOLFOX6 and bevacizumab is FDA approved and commercially available for the treatment of colorectal cancer. Doxorubicin is FDA approved and commercially available for the treatment of ovarian cancer. Bevacizumab is FDA approved and commercially available for the treatment of colorectal cancer. Temsirolimus is FDA approved and commercially available for the treatment of renal cell carcinoma. NovoTTF is an FDA-approved device to treat glioblastomas.

The use of the study drugs in combination with the NovoTTF system to treat cancer that has spread to the liver is investigational.

The combination of liposomal doxorubicin, bevacizumab, and temsirolimus is investigational and not approved for the treatment of any cancer type. The combination is currently being used for research purposes only.

Up to 52 participants will be enrolled in this study. All will take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Liver Cancer Drug: Oxaliplatin Drug: Leucovorin Drug: 5-fluorouracil Drug: Bevacizumab Device: NovoTTF-100L Drug: Liposomal Doxorubicin Drug: Temsirolimus Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of the NovoTTF-100L System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Arm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System

Participants receive Oxaliplatin, Leucovorin, 5-fluorouracil, and Bevacizumab by vein on Days 1 and 15 of a 28 day cycle.

NovoTTF-100L system applied to torso where the tumor is located for at least 18 hours a day.

Up to 6 participants enrolled at each dose level. First group of participants enrolled receive a low dose level of the drug. If no bad side effects are seen in this group, the next group will be treated with a higher dose level. This will continue until the highest tolerable dose level of the combination is found. After highest tolerable dose of combination is found, additional participants enrolled at this level to further study the safety of this drug combination.

Drug: Oxaliplatin

Arm A: Dose Escalation Group Starting Dose of Oxaliplatin: 85 mg/m2 by vein on Days 1 and 15 of a 28 day cycle.

Dose Expansion Group Starting Dose of Oxaliplatin: Maximum tolerated dose from Dose Escalation Group.

Other Name: Eloxatin

Drug: Leucovorin

Dose Escalation Group Starting Dose of Leucovorin: 400 mg/m2 by vein on Days 1 and 15 of a 28 day cycle.

Dose Expansion Group Starting Dose of Leucovorin: Maximum tolerated dose from Dose Escalation Group.

Other Names:
  • Citrovorum
  • Wellcovorin

Drug: 5-fluorouracil

Dose Escalation Group Starting Dose of 5-fluorouracil: 400 mg/m2 by vein on Days 1 and 15 of a 28 day cycle.

Dose Expansion Group Starting Dose of 5-fluorouracil: Maximum tolerated dose from Dose Escalation Group.

Other Names:
  • Fluorouracil
  • 5-FU
  • Adrucil
  • Efudex

Drug: Bevacizumab

Arm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System Dose Escalation Group Starting Dose of Bevacizumab: 5 mg/kg by vein on Days 1 and 15 of a 28 day cycle.

Arm B: DAT + NovoTTF-100L System Dose Escalation Group Starting Dose of Bevacizumab: 10 mg/kg by vein on Days 1 and 15 of a 28 day cycle.

mFOLFOX6 + Bevacizumab + NovoTTF-100L System Dose Expansion Group Starting Dose of Bevacizumab: Maximum tolerated dose from Dose Escalation Group.

DAT + NovoTTF-100L System Dose Escalation Group Starting Dose of Bevacizumab: 10 mg/kg by vein on Days 1 and 15 of a 28 day cycle.

DAT + NovoTTF-100L System Dose Expansion Group Starting Dose of Bevacizumab: Maximum tolerated dose from Dose Escalation Group.

Other Names:
  • Avastin
  • Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF

Device: NovoTTF-100L

NovoTTF-100L system applied to torso where the tumor is located for at least 18 hours a day.

NovoTTF-100L system delivers 100 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 1414mA RMS.


Experimental: Arm B: DAT + NovoTTF-100L System

Participants receive Liposomal Doxorubicin and Bevacizumab by vein on Days 1 and 15 of a 28 day cycle. Temsirolimus given by vein on Days 1, 8, 15, and 22 of a 28 day cycle.

NovoTTF-100L system applied to torso where the tumor is located for at least 18 hours a day.

Up to 6 participants enrolled at each dose level. First group of participants enrolled receive a low dose level of the drug. If no bad side effects are seen in this group, the next group will be treated with a higher dose level. This will continue until the highest tolerable dose level of the combination is found. After highest tolerable dose of combination is found, additional participants enrolled at this level to further study the safety of this drug combination.

Drug: Bevacizumab

Arm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System Dose Escalation Group Starting Dose of Bevacizumab: 5 mg/kg by vein on Days 1 and 15 of a 28 day cycle.

Arm B: DAT + NovoTTF-100L System Dose Escalation Group Starting Dose of Bevacizumab: 10 mg/kg by vein on Days 1 and 15 of a 28 day cycle.

mFOLFOX6 + Bevacizumab + NovoTTF-100L System Dose Expansion Group Starting Dose of Bevacizumab: Maximum tolerated dose from Dose Escalation Group.

DAT + NovoTTF-100L System Dose Escalation Group Starting Dose of Bevacizumab: 10 mg/kg by vein on Days 1 and 15 of a 28 day cycle.

DAT + NovoTTF-100L System Dose Expansion Group Starting Dose of Bevacizumab: Maximum tolerated dose from Dose Escalation Group.

Other Names:
  • Avastin
  • Anti-VEGF Monoclonal Antibody
  • rhuMab-VEGF

Device: NovoTTF-100L

NovoTTF-100L system applied to torso where the tumor is located for at least 18 hours a day.

NovoTTF-100L system delivers 100 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 1414mA RMS.


Drug: Liposomal Doxorubicin

Dose Escalation Group Starting Dose of Liposomal Doxorubicin: 20 mg/m2 by vein on Days 1 and 15 of a 28 day cycle.

Dose Expansion Group Starting Dose of Liposomal Doxorubicin: Maximum tolerated dose from Dose Escalation Group.

Other Names:
  • Doxil
  • Doxorubicin Hydrochloride (Liposomal)

Drug: Temsirolimus

Dose Escalation Group Starting Dose of Temsirolimus: 25 mg by vein on Days 1, 8, 15, and 22 of a 28 day cycle.

Dose Expansion Group Starting Dose of Temsirolimus: Maximum tolerated dose from Dose Escalation Group.

Other Names:
  • CCI-779
  • Torisel




Primary Outcome Measures :
  1. Maximum Tolerated Doses of Two Established Chemotherapy Regimens in Combination with Concurrent use of NovoTTF-100L System [ Time Frame: 28 days ]
    Maximum tolerated dose (MTD) defined by dose limiting toxicities (DLTs) that occur in the first 28 days. Expected toxicity rate at MTD is approximately 33%. Dose-limiting toxicity (DLT) defined if events occur within first cycle (28 days). DLT defined as treatment-related ≥ Grade 3 non-hematological toxicity other than grade 3 nausea and vomiting that can be controlled at 72 hours with appropriate antiemetic therapy, grade 3 fatigue, or grade 3 clinically insignificant electrolyte abnormalities.


Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 4 months ]
    Categorization of response based on RECIST 1.1.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with advanced malignancies, either refractory to standard therapy or for which no effective standard therapy is available, unless the drugs in the protocol are part of the standard of care for a specific diagnosis.Predominant hepatic metastasis is defined as at least 50% of the total tumor burden involving the liver. For patients who are enrolled into the arm of mFOLFOX6 plus Bevacizumab, they must have metastatic colorectal cancer with predominant hepatic metastases.For patients who are enrolled into the arm of DAT, they must have predominant hepatic metastases harboring an aberrant PI3K pathway detected in a CLIA-certified laboratory.
  2. Patients must have measurable or evaluable disease, as defined by RECIST 1.1.
  3. Men or women aged greater or equal than18 years
  4. Women of child-bearing potential (women who are not postmenopausal for at least one year or are not surgically sterile) and men must agree to use adequate contraception (e.g., hormonal, barrier device, or abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose the study agents.
  5. Patients must have an ECOG performance status of 0 to 2.
  6. Patients must have adequate organ functions as defined below: Neutrophils greater or equal than 1,500 /microliter. Platelets greater or equal than 100,000 /microliter. Total bilirubin smaller or equal than 1.5 x ULN (upper limit of normal) (except patients with Gilbert's syndrome, who must have a total bilirubin smaller or equal than 3.0 mg/dL). ALT smaller or equal than 3 x ULN or smaller or equal than 5 x ULN if liver metastases persist. Serum creatinine smaller or equal than 1.5 mg/dL or calculated creatinine clearance greater or equal than 50 mL/minutes
  7. Patients should be able to read and fully understand the requirements of the trial, be willing to comply with all trial visits and assessments, and be willing and able to sign an IRB-approved written informed consent document.
  8. Patients may receive palliative radiation therapy immediately before or during the treatment if the radiation therapy is not delivered to the sole target lesions.

Exclusion Criteria:

  1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, uncontrolled systemic hypertension (systolic BP > 140 mm Hg, diastolic BP > 90 mm Hg), left ventricular ejection fraction < 50%, active bleeding, or psychiatric illness/social situations that would limit compliance with study requirements.
  2. Patients who have not recovered from major surgical procedure, or significant traumatic injury (i.e., patients still need additional medical care for these issues).
  3. History of allergic reactions to the study drugs or their analogs, or any component of the products, or sensitive to conductive hydrogels used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes.
  4. Any treatment specific for tumor control within 3 weeks of drugs; or within 2 weeks if cytotoxic agents were given weekly (within 6 weeks for nitrosoureas or mitomycin C), or within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting fewer than 4 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and similar agents), or failure to recover from the toxic effect of any of these therapies prior to study entry.
  5. Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids.
  6. Implanted pacemaker, defibrillator, nerve stimulator or other active electronic medical devices.
  7. QTc is greater than 480 milliseconds (msec) at screening, or documented clinically significant arrhythmias. The QTc formula Bazett will be used for assessing subject eligibility.
  8. History of stroke or transient ischemic attack, peripheral vascular disease, active gastric or duodenal ulcer, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
  9. Patients with known human immunodeficiency virus infection, active hepatitis B or C.
  10. Women who are pregnant will be excluded from the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03203525


Contacts
Layout table for location contacts
Contact: Siqing Fu, MD, PHD 713-792-4318 siqingfu@mdanderson.org

Locations
Layout table for location information
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact       siqingfu@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
NovoCure Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Siqing Fu, MD, PHD M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03203525     History of Changes
Other Study ID Numbers: 2014-0357
NCI-2018-01558 ( Registry Identifier: NCI CTRP )
First Posted: June 29, 2017    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Advanced liver cancer
Liver Cancer
Hepatic metastases
Eloxatin
Oxaliplatin
Leucovorin
Citrovorum
Wellcovorin
5-fluorouracil
Fluorouracil
5-FU
Adrucil
Efudex
Bevacizumab
Avastin
Anti-VEGF monoclonal antibody
rhuMab-VEGF
Liposomal Doxorubicin
Doxil
Doxorubicin Hydrochloride (Liposomal)
Temsirolimus
CCI-779
Torisel
NovoTTF-100L System
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Neoplasms
Neoplasm Metastasis
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Neoplastic Processes
Pathologic Processes
Leucovorin
Sirolimus
Bevacizumab
Oxaliplatin
Doxorubicin
Liposomal doxorubicin
Fluorouracil
Everolimus
Antibodies
Antibodies, Monoclonal
Levoleucovorin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunologic Factors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors