Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib or With Pembrolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax
2 other identifiers
interventional
43
1 country
1
Brief Summary
This phase Ib trial tests the safety, side effects, and best dose of tumor treating fields therapy in combination with either cabozantinib or nab-paclitaxel and atezolizumab in treating patients with solid tumors involving the abdomen or thorax that have spread to other parts of the body (advanced). Tumor treating fields therapy on this study utilizes NovoTTF systems that are wearable devices that use electrical fields at different frequencies that may help stop the growth of tumor cells by interrupting cancer cells' ability to divide. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Chemotherapy drugs, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tumor treating fields therapy in combination with either cabozantinib, or with nab-paclitaxel and atezolizumab may help control advanced solid tumors involving the abdomen or thorax.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 13, 2021
CompletedFirst Posted
Study publicly available on registry
October 25, 2021
CompletedStudy Start
First participant enrolled
April 29, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2026
January 14, 2026
January 1, 2026
4.3 years
October 13, 2021
January 13, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
To assess the safety and tolerability of TTF, including the maximum tolerated dose (MTD).
To assess the safety and tolerability of TTF, including the maximum tolerated dose (MTD),in combination with cabozantinib (Cohort 1) or with nab-paclitaxel and atezolizumab (Cohort 2) in patients with advanced solid tumors involving the abdomen or thorax to the 4 prespecified tumor types. 1st cycle with at least 6 evaluable patients treated at the dose.
through study completion, an average of 2 to 3 years
Secondary Outcomes (1)
To assess the objective response rate, progression-free survival and overall survival
through study completion, an average of 2 to 3 years
Study Arms (2)
Cohort 1 (TTF, cabozantinib)
EXPERIMENTALPatients receive TTF continuously for at least 18 hours per day on days 1-21 of each cycle. Patients also receive cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohort 2 (TFF, atezolizumab, nab-paclitaxel)
EXPERIMENTALPatients receive TTF continuously for at least 18 hours per day on days 1-28 of each cycle. Patients also receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 of each cycle and atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Given IV
Receive TTF
Eligibility Criteria
You may qualify if:
- Participants must have pathologically confirmed advanced/metastatic solid cancer (hepatocellular carcinoma, renal cell carcinoma, breast cancer, ovarian/fallopian, or endometrial/primary peritoneal tumors) involving the abdomen or thorax, cannot tolerate standard therapy or have experienced tumor progression on standard therapy.
- Age: ≥18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Life expectancy \>3 months.
- Normal bone marrow function, defined as absolute neutrophil count ≥1,000/µL; platelets ≥75,000/µL; hemoglobin ≥8 g/dL.
- Adequate hepatic function as defined by a total bilirubin level ≤1.5 x the upper limit of normal (ULN), unless the patient has known Gilbert's syndrome, and alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase levels (SGPT) ≤2.5 x ULN (unless the patient has liver metastases: ALT)/ serum glutamic pyruvic transaminase levels (SGPT) ≤5 x ULN).
- Participants with HCC must have a Child Pugh status A, no clinically significant ascites (requiring pharmacological or interventional treatment), and no history (or increased risk) of esophageal/gastric bleeding, impaired wound healing, perforation or fistula.
- Serum creatinine clearance ≥50 mL/min by the Cockcroft-Gault formula.
- Measurable disease by RECIST or evaluable disease.
- Contraception: Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months and who have not had a tubal ligation, hysterectomy, or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. Male participants must agree to use effective contraception or abstinence while on study.
- Able to operate the TTF device independently or with the help of a caregiver.
You may not qualify if:
- Participants must not receive prior anticancer therapy or radiation therapy within 2 weeks and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Participants who are already on cabozantinib and have progressive disease are allowed to transition to treatment with tumor treating fields and cabozantinib. Participants in both cohorts who already started treatments as standard of care (Cohort 1: Cabozantinib and Cohort 2: nab-paclitaxel and Pembrolizumab) are allowed to start on protocol within the first 2-3 weeks of treatment initiation. Palliative radiation therapy is allowed.
- Participants must have recovered to Grade 0-1 toxicity from prior therapy.
- Active brain metastasis or leptomeningeal disease. Patients with treated brain metastasis must have stable disease, evidenced by brain imaging for at least 4 weeks and the patient must have been off steroids for at least 2 weeks.
- The patient has cardiac conditions as follows: uncontrolled: hypertension (blood pressure \[BP\] \> 160/100) despite optimal therapy, uncontrolled angina, ventricular arrhythmias, congestive heart failure (New York Heart Association Class II or above), prior or current cardiomyopathy, uncontrolled atrial fibrillation with heart rate \> 100 beats per minute (bpm), unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment or angina requiring use of nitrates more than once weekly).
- The patient has concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes, severe infection requiring active treatment, severe malnutrition, chronic severe liver or renal disease).
- Concurrent malignancies are permitted if (A) they were previously treated, and all treatment of that malignancy was completed at least 2 years before enrollment and no evidence of disease exists, or (B) with agreement from the Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible to participate if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low, or (C) with agreement from the PI, other malignancies may be permitted if the risk of the prior malignancy interfering with either safety or efficacy end points is very low. Adequately treated basal or squamous cell carcinoma or carcinoma in situ is allowed.
- The patient is pregnant or breastfeeding.
- History of hypersensitivity or contraindication to TTF.
- Implanted pacemaker, defibrillator or other electrical medical devices.
- The participant has a previously-identified allergy or hypersensitivity to cabozantinib, nab-paclitaxel, or pembrolizumab, medical adhesives or hydrogel or the patient has received prior cabozantinib and discontinued therapy due to unacceptable toxicity.
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- The patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
- CABOZANTINIB COHORT ONLY: The patient has experienced clinically-significant hematemesis or hemoptysis of \> 0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment.
- CABOZANTINIB COHORT ONLY: The patient has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel.
- CABOZANTINIB COHORT ONLY: The patient has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Apostolia M Tsimberidou
M.D. Anderson Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 13, 2021
First Posted
October 25, 2021
Study Start
April 29, 2022
Primary Completion (Estimated)
September 1, 2026
Study Completion (Estimated)
September 1, 2026
Last Updated
January 14, 2026
Record last verified: 2026-01