- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03203525
Combination Chemotherapy and Bevacizumab With the NovoTTF-100L(P) System in Treating Participants With Advanced, Recurrent, or Refractory Hepatic Metastatic Cancer
A Phase I Study of the NovoTTF-100L(P) System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Siqing Fu
- Phone Number: 713-792-4318
- Email: siqingfu@mdanderson.org
-
Principal Investigator:
- Siqing Fu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (FOLFOX6, bevacizumab, NovoTTF-100L[P])
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.
|
Given IV
Other Names:
Given via pump
Other Names:
Given via pump
Other Names:
Given via pump
Other Names:
Use NovoTTF-100L(P) system
Other Names:
|
Experimental: Arm B(bevacizumab,liposomal doxorubicin, DAT, NovoTTF-100L[P])
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.
|
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Use NovoTTF-100L(P) system
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events
Time Frame: Up to 3 years
|
Descriptive statistics will be provided on the grade and type of toxicity by dose level.
|
Up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response
Time Frame: Up to 3 years
|
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.
|
Up to 3 years
|
Biomarker analysis
Time Frame: Up to 3 years
|
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.
|
Up to 3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Siqing Fu, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Neoplastic Processes
- Neoplasms
- Colorectal Neoplasms
- Neoplasm Metastasis
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Micronutrients
- Anti-Bacterial Agents
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Vitamins
- Antifungal Agents
- Antidotes
- Vitamin B Complex
- Antibodies
- Fluorouracil
- Oxaliplatin
- Immunoglobulins
- Bevacizumab
- Leucovorin
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Sirolimus
- Immunoglobulin G
- Endothelial Growth Factors
- Temsirolimus
- MTOR Inhibitors
Other Study ID Numbers
- 2014-0357 (Other Identifier: M D Anderson Cancer Center)
- P30CA016672 (U.S. NIH Grant/Contract)
- NCI-2018-01597 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Malignant Neoplasm in the Liver
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the Liver | Metastatic Malignant Neoplasm in the LungUnited States
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the Liver | Unresectable Solid NeoplasmUnited States, Canada
-
M.D. Anderson Cancer CenterActive, not recruitingAdvanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Carcinoma in the Liver | Metastatic Carcinoma in the Lung | Metastatic Malignant Neoplasm in the Thoracic CavityUnited States
-
NRG OncologyNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Metastatic Malignant Neoplasm in the Bone | Metastatic Malignant Neoplasm in the Lymph Nodes | Metastatic Malignant Neoplasm in the Liver | Metastatic Breast Carcinoma | Metastatic Malignant Neoplasm in the Lung and other conditionsUnited States, Canada, Saudi Arabia, Korea, Republic of
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingMetastatic Malignant Neoplasm in the Bone | Metastatic Malignant NeoplasmUnited States
-
Sameek RoychowdhuryNational Cancer Institute (NCI)WithdrawnLocally Advanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | ALK Gene Mutation | Metastatic Malignant Neoplasm in the Brain | Advanced Malignant Neoplasm | ALK Fusion Protein Expression | Metastatic Malignant Neoplasm in the Central Nervous System | ROS1 Gene Mutation | ALK Gene... and other conditionsUnited States
-
M.D. Anderson Cancer CenterWithdrawnLocally Advanced Malignant Solid Neoplasm | Recurrent Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Metastatic Malignant Neoplasm in the Bone
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingMalignant Solid Neoplasm | Metastatic Malignant Neoplasm in the BrainUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMalignant Neoplasm | Metastatic Malignant Neoplasm in the BrainUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingPain | Metastatic Malignant Neoplasm in the Bone | Malignant NeoplasmUnited States
Clinical Trials on Pegylated Liposomal Doxorubicin Hydrochloride
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast Carcinoma | Male Breast Carcinoma | Stage IV Breast Cancer AJCC...United States
-
National Cancer Institute (NCI)CompletedDS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
ARCAGY/ GINECO GROUPCompleted
-
European Organisation for Research and Treatment...CompletedBreast CancerFrance, Spain, Netherlands, United Kingdom, Italy, Israel, Switzerland, Greece, Austria
-
European Organisation for Research and Treatment...CompletedLymphomaGermany, Switzerland, Israel, United Kingdom, Austria, Italy
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedSarcoma | Endometrial CancerUnited States, Canada
-
University of LeicesterUnknownGastric Cancer | Esophageal CancerUnited Kingdom
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedEndometrial CancerUnited States
-
Merck Sharp & Dohme LLCCompleted
-
Brown UniversityUnknownLiver Cancer | Gallbladder Cancer | Extrahepatic Bile Duct CancerUnited States