Combination Chemotherapy and Bevacizumab With the NovoTTF-100L(P) System in Treating Participants With Advanced, Recurrent, or Refractory Hepatic Metastatic Cancer
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| ClinicalTrials.gov Identifier: NCT03203525 |
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Recruitment Status :
Recruiting
First Posted : June 29, 2017
Last Update Posted : January 5, 2023
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Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Malignant Neoplasm Colorectal Carcinoma Metastatic in the Liver Metastatic Malignant Neoplasm in the Liver Refractory Malignant Neoplasm | Biological: Bevacizumab Drug: Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Drug: Pegylated Liposomal Doxorubicin Hydrochloride Drug: Temsirolimus Procedure: Tumor Treating Fields Therapy | Phase 1 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 52 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase I Study of the NovoTTF-100L(P) System to Enhance Antitumor Activity in Patients With Predominant Hepatic Metastatic Cancer |
| Actual Study Start Date : | June 23, 2020 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2023 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Bevacizumab
| Arm | Intervention/treatment |
|---|---|
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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.
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Biological: Bevacizumab
Given IV
Other Names:
Drug: Fluorouracil Given via pump
Other Names:
Drug: Leucovorin Given via pump
Other Name: folinic acid Drug: Oxaliplatin Given via pump
Other Names:
Procedure: Tumor Treating Fields Therapy Use NovoTTF-100L(P) system
Other Names:
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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.
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Biological: Bevacizumab
Given IV
Other Names:
Drug: Pegylated Liposomal Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Temsirolimus Given IV
Other Names:
Procedure: Tumor Treating Fields Therapy Use NovoTTF-100L(P) system
Other Names:
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Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03203525
Locations
| United States, Texas | |
| M D Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Siqing Fu 713-792-4318 siqingfu@mdanderson.org | |
| Principal Investigator: Siqing Fu | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Siqing Fu | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT03203525 |
| Other Study ID Numbers: |
2014-0357 NCI-2018-01597 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2014-0357 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
| First Posted: | June 29, 2017 Key Record Dates |
| Last Update Posted: | January 5, 2023 |
| Last Verified: | November 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Neoplasms Neoplasm Metastasis Colorectal Neoplasms Neoplastic Processes Pathologic Processes Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Leucovorin |
Sirolimus Bevacizumab Antineoplastic Agents, Immunological Doxorubicin Liposomal doxorubicin Fluorouracil Oxaliplatin Endothelial Growth Factors Antibodies Immunoglobulins Antibodies, Monoclonal Immunoglobulin G Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents |