Clinical Trials /

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

NCT03203525

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of the NovoTTF-100L System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer
  • Official Title: A Phase I Study of the NovoTTF-100L System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2014-0357
  • SECONDARY ID: NCI-2018-01558
  • NCT ID: NCT03203525

Conditions

  • Liver Cancer

Interventions

DrugSynonymsArms
OxaliplatinEloxatinArm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System
LeucovorinCitrovorum, WellcovorinArm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System
5-fluorouracilFluorouracil, 5-FU, Adrucil, EfudexArm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System
BevacizumabAvastin, Anti-VEGF Monoclonal Antibody, rhuMab-VEGFArm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L System
Liposomal DoxorubicinDoxil, Doxorubicin Hydrochloride (Liposomal)Arm B: DAT + NovoTTF-100L System
TemsirolimusCCI-779, ToriselArm B: DAT + NovoTTF-100L System

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm A: mFOLFOX6 + Bevacizumab + NovoTTF-100L SystemExperimentalParticipants 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.
  • Oxaliplatin
  • Leucovorin
  • 5-fluorouracil
  • Bevacizumab
Arm B: DAT + NovoTTF-100L SystemExperimentalParticipants 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.
  • Bevacizumab
  • Liposomal Doxorubicin
  • Temsirolimus

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Doses of Two Established Chemotherapy Regimens in Combination with Concurrent use of NovoTTF-100L System
Time Frame:28 days
Safety Issue:
Description: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

Measure:Response Rate
Time Frame:4 months
Safety Issue:
Description:Categorization of response based on RECIST 1.1.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Liver Cancer
  • Hepatic metastases
  • Advanced liver cancer
  • 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

Last Updated

January 7, 2019