search
Back to results

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

Primary Purpose

Advanced Malignant Neoplasm, Colorectal Carcinoma Metastatic in the Liver, Metastatic Malignant Neoplasm in the Liver

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Fluorouracil
Leucovorin
Oxaliplatin
Pegylated Liposomal Doxorubicin Hydrochloride
Temsirolimus
Tumor Treating Fields Therapy
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignant Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Sites / Locations

  • M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A (FOLFOX6, bevacizumab, NovoTTF-100L[P])

Arm B(bevacizumab,liposomal doxorubicin, DAT, NovoTTF-100L[P])

Arm Description

Participants receive oxaliplatin, leucovorin, and fluorouracil via pump over 46 hours on beginning on day 1, bevacizumab 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.

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.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Descriptive statistics will be provided on the grade and type of toxicity by dose level.

Secondary Outcome Measures

Response
Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Wilcoxon's Signed-Rank Test and Fisher's exact test will be used for data analysis of continuous variables and categorical variables, respectively. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.
Biomarker analysis
Wilcoxon's Signed-Rank Test and Fisher's exact test will be used for data analysis of continuous variables and categorical variables, respectively. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.

Full Information

First Posted
June 27, 2017
Last Updated
June 6, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT03203525
Brief Title
Combination Chemotherapy and Bevacizumab With the NovoTTF-100L(P) System in Treating Participants With Advanced, Recurrent, or Refractory Hepatic Metastatic Cancer
Official Title
A Phase I Study of the NovoTTF-100L(P) System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 23, 2020 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed Description
PRIMARY OBJECTIVES: I. To define the maximum tolerated doses (MTD) of two established chemotherapy regimens (Arm A: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Malignant Neoplasm, Colorectal Carcinoma Metastatic in the Liver, Metastatic Malignant Neoplasm in the Liver, Refractory Malignant Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (FOLFOX6, bevacizumab, NovoTTF-100L[P])
Arm Type
Experimental
Arm Description
Participants receive oxaliplatin, leucovorin, and fluorouracil via pump over 46 hours on beginning on day 1, bevacizumab 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 Title
Arm B(bevacizumab,liposomal doxorubicin, DAT, NovoTTF-100L[P])
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-fluorouracil, 5-Fluracil, 5-FU, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757
Intervention Description
Given via pump
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
folinic acid
Intervention Description
Given via pump
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Other Intervention Name(s)
1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669
Intervention Description
Given via pump
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin Hydrochloride
Other Intervention Name(s)
ATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposomal, Doxorubicin HCl Liposome, Doxorubicin Hydrochloride Liposome, Duomeisu, Evacet, LipoDox, Lipodox 50, Liposomal Adriamycin, Liposomal Doxorubicin Hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Temsirolimus
Other Intervention Name(s)
CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog, Rapamycin Analog CCI-779, Torisel
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Tumor Treating Fields Therapy
Other Intervention Name(s)
Alternating Electric Field Therapy, TTF, TTFields
Intervention Description
Use NovoTTF-100L(P) system
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Descriptive statistics will be provided on the grade and type of toxicity by dose level.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Response
Description
Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Wilcoxon's Signed-Rank Test and Fisher's exact test will be used for data analysis of continuous variables and categorical variables, respectively. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.
Time Frame
Up to 3 years
Title
Biomarker analysis
Description
Wilcoxon's Signed-Rank Test and Fisher's exact test will be used for data analysis of continuous variables and categorical variables, respectively. A mixed model accounting for patient effects will be used to analyze longitudinal data (including biomarker data) over time.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Siqing Fu
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Siqing Fu
Phone
713-792-4318
Email
siqingfu@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Siqing Fu

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs