Combination Chemotherapy and Bevacizumab with the NovoTTF-100L System in Treating Participants with Advanced, Recurrent, or Refractory Hepatic Metastatic Cancer

Status: Approved

Description

This phase I trial studies the side effects and best dose of combination chemotherapy and bevacizumab, and to see how well they work with the NovoTTF-100L system in treating participants with cancer that has come back or does not respond to treatment and has spread to the liver. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, fluorouracil, pegylated liposomal doxorubicin hydrochloride, and temsirolimus, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. The NovoTTF-100L system is a portable device that uses electrical fields to stop the growth of tumor cells. Giving combination chemotherapy and monoclonal antibody therapy while using the NovoTTF-100L system may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Patients with advanced malignancies, either refractory to standard therapy or for which no effective standard therapy that increases survival for > 3 months 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 Clinical Laboratory Improvement Act (CLIA)-certified laboratory or with the tumor type that showed meaningfully clinical benefit to the treatment with DAT
  • Patients must have measurable or evaluable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • 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
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • 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)
  • Alanine aminotransferase (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
  • 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 Institutional Reviewed Board (IRB)-approved written informed consent document
  • 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

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, uncontrolled systemic hypertension (systolic blood pressure [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
  • Patients who have not recovered from major surgical procedure, or significant traumatic injury (i.e., patients still need additional medical care for these issues)
  • 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
  • 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
  • Symptomatic primary tumors or metastasis of brain and/or central nervous system that are uncontrolled with antiepileptics and requiring high doses of steroids
  • Implanted pacemaker, defibrillator, nerve stimulator or other active electronic medical devices
  • Corrected QT interval (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
  • 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
  • Patients with known human immunodeficiency virus infection, active hepatitis B or C
  • Women who are pregnant will be excluded from the study

Locations & Contacts

Texas

Houston
M D Anderson Cancer Center
Status: Approved
Contact: Siqing Fu
Phone: 713-792-4318

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To define the maximum tolerated doses (MTD) of two established chemotherapy regimens (Arm A: mFOLFOX6 [oxaliplatin, fluorouracil (5FU) and leucovorin (folinic acid)] plus bevacizumab; and Arm B: pegylated liposomal doxorubicin hydrochloride [liposomal doxorubicin] and bevacizumab plus temsirolimus [DAT]) in combination with the concurrent use of the NovoTTF-100L system in patients with predominant hepatic metastases.

II. To define the safety profiles of mFOLFOX6 plus bevacizumab or DAT with concurrent NovoTTF-100L in patients with predominant hepatic metastases.

SECONDARY OBJECTIVES:

I. To evaluate clinical response signals to the treatment with mFOLFOX6 plus bevacizumab or DAT with concurrent NovoTTF-100L.

II. To assess predictive biomarkers by analyzing baseline molecular mutation status, and resistant pathways by comparing molecular signatures at baseline versus at time of relapse in patients who have achieved objective responses.

III. To assess overall clinical response including response of liver lesions, and/or response of non-liver metastases.

OUTLINE: This is a dose-escalation study. Participants are assigned to 1 of 2 arms.

ARM A: Participants receive oxaliplatin, leucovorin, and fluorouracil via pump over 46 hours beginning on day 1, bevacizumab intravenously (IV) over 30-90 minutes on day 15, and use NovoTTF-100L system over 18 hours daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Participants receive bevacizumab IV over 90 minutes on days 1 and 15, pegylated liposomal doxorubicin hydrochloride IV over 30 minutes-3 hours on days 1 and 15, and temsirolimus IV over 60-90 minutes on days 1, 8, 15, and 22. Participants also use NovoTTF-100L system over 18 hours daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
M D Anderson Cancer Center

Principal Investigator
Siqing Fu

Trial IDs

Primary ID 2014-0357
Secondary IDs NCI-2018-01597
Clinicaltrials.gov ID NCT03203525