Phase I Study of Tumor Treating Fields (TTF) in Combination With Cabozantinib, or With Atezolizumab and Nab-Paclitaxel in Patients With Advanced Solid Tumors Involving the Abdomen or Thorax

• Status: Not yet recruiting
• Trial end date: 2026-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an investigator-initiated industry-supported phase I clinical trial conducted in the phase I clinic, MD Anderson Cancer Center. The study consists of two parts: dose finding (MTD (maximum tolerated dose) determination) and dose expansion parts.

The safety and tolerability of TTF 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 will be evaluated. Patients with HCC and renal carcinoma will be included in cohort 1 and treated with TTF (150 kHz frequency for HCC and 200 kHz for renal cell carcinoma) in combination with cabozantinib. Patients with breast cancer and gynecologic tumors (ovarian/fallopian, endometrial/primary peritoneal tumors) will be included in cohort 2 and treated with TTF (150 kHz frequency for breast cancer and 200 kHz for gynecologic tumors) with nab-paclitaxel and atezolizumab.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Treatments: Albumin-Bound Paclitaxel; Atezolizumab; Paclitaxel

Criteria

Inclusion Criteria:

To be eligible for this trial, patients must meet all of the following eligibility criteria:

• Patients must have pathologically confirmed advanced/metastatic cancer involving the abdomen or thorax.

• 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).

• 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 subjects 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.

Exclusion Criteria:

Patients who meet any of the following criteria will be not eligible for the study:

• Patients must not receive prior anticancer therapy or radiation therapy within 3 weeks and must not undergo major surgery within 4 weeks prior to initiation of treatment on protocol. Palliative radiation therapy is allowed.

• Patients 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 (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 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 patient has a previously-identified allergy or hypersensitivity to cabozantinib, nab-paclitaxel, or atezolizumab, medical adhesives or hydrogel.

• 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.

Additional Exclusion Criteria for 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.

• The patient has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel.

• The patient has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment.

• The patient has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3X) the laboratory upper limit of normal.

• The subject has a corrected QT interval (QTcF)>450 ms for men or >470 ms for women.

• The patient requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents. Low-dose aspirin (≤81 mg/day), low-dose warfarin (≤1mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted.

• Patients with encasement of a major artery or bowel by tumor are excluded.

• The patient is unable to swallow capsules.

• History of hypersensitivity or contraindication to cabozantinib.

Additional Criteria for Atezolizumab-Containing Cohort (Atezolizumab and Nab-Paclitaxel)

Inclusion:

-PD-L1 expression on tumor-infiltrating immune cells positive (≥1% PD-L1) by immunohistochemical testing.

Exclusion Criteria:

• Participants who have received prior immunotherapy, including prior anti-PD-1 or anti-PD-L1 therapies may participate: (A) only if their prior anti-PD-1 or anti-PD-L1 monotherapy or combination therapy were NOT the last treatment prior to participation on this study. (B) Participants who had prior immunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) must have documentation that their irAEs are Grade 1 or 0 using current Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must be off steroid therapy and/or other immunosuppressive therapy, as treatment for irAEs, for ≥ 14 days from Cycle 1, Day 1. (C) Participants who experienced Grade 3 irAEs consisting of laboratory abnormalities that were asymptomatic and have now resolved to Grade 1 or 0 and participants who have been off steroid and/or other immunosuppressive therapy, as treatment for irAEs, for ≥ 30 days from Cycle 1, Day 1. Participants with prior irAE pneumonitis (≥ Grade 2) should not be given atezolizumab.

• HIV infection, active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics.

• Has received a live vaccine within 30 days prior to first dose.

• Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.

• Serious autoimmune disease at the discretion of the treating attending: Patients with a history of active serious inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g. Wegener's Granulomatosis] are excluded from this study.

• History of/or current immunodeficiency disease or prior treatment compromising immune function at the discretion of the treating physician.

Criteria for Withdrawal from the Trial for Both Cohorts

Subjects are free to discontinue the trial at any time without giving their reasons.

A subject must be withdrawn in the event of any of the following:

• Withdrawal of subject consent

• Pregnancy

• Participation in any other interventional trial during the duration of this trial

Criteria for Withdrawal from the Cabozantinib Cohort Only

-If significant QTc prolongation or QRS widening is observed on-treatment:

1. Fridericia-corrected QT interval (QTcF) > 500 ms or QTcF > 480 ms (i.e., not Bazett-corrected QT interval) with a concomitant increase from baseline > 60 ms

2. QRS > 120 ms with more than 20 ms increase from baseline

3. If an abnormal ECG interval is observed, recordings should be obtained in triplicate (if possible) and the decision should be based on the average interval of these recordings.

4. If QTc prolongation as described above is observed, electrolytes should be checked and adjusted, if abnormal