| Eligibility |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- CABOZANTINIB COHORT ONLY: 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.
- CABOZANTINIB COHORT ONLY: The subject has a corrected QT interval (QTcF) > 450 ms for
men or > 470 ms for women.
- CABOZANTINIB COHORT ONLY: 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.
- CABOZANTINIB COHORT ONLY: Patients with encasement of a major artery or bowel by tumor
are excluded.
- CABOZANTINIB COHORT ONLY: The patient is unable to swallow capsules.
- CABOZANTINIB COHORT ONLY: History of hypersensitivity or contraindication to
cabozantinib.
- ATEZOLIZUMAB-CONTAINING COHORT: 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-PDL1 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.
- ATEZOLIZUMAB-CONTAINING COHORT: Human immunodeficiency virus (HIV) infection, active
Hepatitis B or C infection, or active infections requiring oral or intravenous
antibiotics.
- ATEZOLIZUMAB-CONTAINING COHORT: Has received a live vaccine within 30 days prior to
first dose.
- ATEZOLIZUMAB-CONTAINING COHORT: Active diverticulitis, intra-abdominal abscess,
gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk
factors for bowel perforation.
- ATEZOLIZUMAB-CONTAINING COHORT: 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.
- ATEZOLIZUMAB-CONTAINING COHORT: History of/or current immunodeficiency disease or
prior treatment compromising immune function at the discretion of the treating
physician.
|
