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
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
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.
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.
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
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
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.