Combination Chemotherapy and Bevacizumab With the NovoTTF-100L(P) System in Treating Participants With Advanced Recurrent or Refractory Hepatic Metastatic Cancer

  • STATUS
    Recruiting
  • End date
    Dec 31, 2021
  • participants needed
    52
  • sponsor
    M.D. Anderson Cancer Center
Updated on 25 January 2021
cancer
absolute neutrophil count
monoclonal antibodies
fluorouracil
metastasis
oxaliplatin
neutrophil count
liver metastasis
tumor cells
leucovorin
metastatic colorectal cancer
bevacizumab
solid tumors
temsirolimus
solid neoplasm
palliative radiation therapy

Summary

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(P) 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. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. The NovoTTF-100L(P) 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(P) system may kill more tumor cells.

Description

PRIMARY OBJECTIVES:

I. To define the maximum tolerated doses (MTD) of two established chemotherapy regimens (Arm

  1. FOLFOX6 [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(P) system in patients with predominant hepatic metastases.

II. To define the safety profiles of FOLFOX6 plus bevacizumab or DAT with concurrent NovoTTF-100L(P) in patients with predominant hepatic metastases.

SECONDARY OBJECTIVES:

I. To evaluate clinical response signals to the treatment with FOLFOX6 plus bevacizumab or DAT with concurrent NovoTTF-100L(P).

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.

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 days 1 and 15, and use NovoTTF-100L(P) 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(P) system over 18 hours daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed at 30 days.

Details
Condition Liver Metastases, Advanced Cancer, Liver Metastasis, Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm in the Liver, Refractory Cancer, Refractory Malignant Neoplasm, Secondary Malignant Neoplasm of Liver, Hepatic Metastases, Cancer Refractory, Colorectal Carcinoma Metastatic in the Liver, cancer advanced
Treatment fluorouracil, pegylated liposomal doxorubicin hydrochloride, bevacizumab, Oxaliplatin, Leucovorin, Temsirolimus, Tumor Treating Fields Therapy
Clinical Study IdentifierNCT03203525
SponsorM.D. Anderson Cancer Center
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Refractory Malignant Neoplasm or Colorectal Carcinoma Metastatic in the Liver or Advanced Malignant Neoplasm or Metastatic Malignant Neoplasm in the L...?
Do you have any of these conditions: Hepatic Metastases or Cancer Refractory or Secondary Malignant Neoplasm of Liver or Advanced Malignant Neoplasm or Refractory Cancer or Colorectal Car...?
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
An aberrant PI3K pathway such as PIK3CA mutations or PTEN loss, is detected in a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory
For patients who are enrolled into the arm of FOLFOX6 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
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 of the study agents
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Neutrophils >= 1,500/uL
Platelets >= 100,000/uL
Total bilirubin =< 1.5 x ULN (upper limit of normal) (except patients with Gilbert's syndrome, who must have a total bilirubin =< 3.0 mg/dL)
Alanine aminotransferase (ALT) =< 3 x ULN or =< 5 x ULN if liver metastases persist
Serum creatinine =< 1.5 mg/dL or calculated creatinine clearance >= 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
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