| Eligibility |
Inclusion Criteria:
- Patient must have histologically or cytologically confirmed metastatic cancer and be
receiving standard of care immunotherapy (PD1/PD-L1 based therapy alone or in
combination with other agents (i.e. chemotherapy, targeted therapy, CTLA-4 agent)
- Patient must have had >= 70% of planned dosing schedule of PD1/PD-L1 based therapy
over the prior treatment period, defined as the previous 3 months
- For example, the expected number of doses in three months for nivolumab dosed
every 2 weeks would be 6 infusions. If the patient were able to receive 5 out of
the 6 doses (83% of planned dosing schedule), they would be eligible for the
protocol. If the patient received only 4 out of the planned 6 doses (67% of
planned dosing schedule), they would be ineligible for the protocol
- Immunotherapy treatment must have been given within the last 4 weeks without the need
for systemic steroid therapy (excluding physiologic doses not to exceed <<10 mg/day>>
of prednisone or its equivalent)
- Patient must have demonstrated prior clinical benefit to PD1/PD-L1 based therapy
followed by progression as defined by RECIST1.1: 1) partial response (PR) or complete
response (CR) by RECIST1.1 (then progression by RECIST1.1) 2) stable disease (SD) x 6
months (then progression by RECIST1.1)
- Patient must have at least two lesions not previously treated with loco-regional
therapy (including external beam radiation, embolization (bland or chemo), Y90, prior
ablation (i.e. microwave, radiofrequency ablation, cryoablation, irreversible
electroporation) that can be accurately measured in at least one dimension (longest
diameter to be recorded) as >=10 mm with spiral computed tomography [CT] scan or >= 20
mm with magnetic resonance imaging [MRI])
- Patient must not have a contraindication to continuing on their current immunotherapy
dose regimen for at least 3 months post-cryoablation
- All lines of prior therapy accepted. Patients with resections of metastatic disease
will be included
- Life expectancy of greater than 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Total bilirubin < 1.5 X institutional normal limits (subjects with known Gilbert
syndrome are eligible with total bilirubin < 3.0 mg/dL)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 X institutional upper limit of normal
- Creatinine within normal institutional limits OR - creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply: Women < 50 years of age would be considered
post-menopausal if they have been amenorrheic for 12 months or more following
cessation of exogenous hormonal treatments and if they have luteinizing hormone and
follicle-stimulating hormone levels in the post-menopausal range for the institution
or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy,
tubal ligation or hysterectomy)
- Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients. Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. Women >= 50 years
of age would be considered post-menopausal if they have been amenorrheic for 12 months
or more following cessation of all exogenous hormonal treatments, had
radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced
menopause with last menses > 1 year ago, or underwent surgical sterilization
(bilateral oophorectomy, bilateral salpingectomy, tubal ligation or hysterectomy)
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Prior immune-related drug toxicity related adverse events that have not recovered to
baseline or grade 1 (alopecia excluded)
- Patient may not be receiving any other investigational agents
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
arthritis, hypophysitis, uveitis, etc]) that require treatment with a disease
modifying agent.
- The following are exceptions:
- Patients with the above disorders may be considered upon principal
investigator (PI) review and allowance (i.e. patient had an autoimmune or
inflammatory disorder but despite the diagnosis has been tolerating
immunotherapy)
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Current use of immunosuppressive medication including for the treatment of severe
immune toxicity related to PD1/PD-L1 based therapy that precludes further treatment
with immunotherapy agents. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, interstitial lung disease, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements
- History of active primary immunodeficiency
- Pregnant or nursing women; women of childbearing potential unless using effective
contraception as determined by the investigator
- Receipt of a live vaccine within 30 days of study entry
- Any concurrent hormonal therapy for cancer treatment. Concurrent use of hormonal
therapy for non-cancer related conditions (e.g. hormone replacement therapy) is
acceptable
- Patient who does not have lesions suitable for biopsy and cryoablation or measurable
disease (non-ablated lesion)
- The lesion being considered for cryoablation must not have undergone prior local
therapy (radiation treatment, embolization (including bland embolization or
chemoembolization), yttrium therapy, prior ablation of any modality (microwave,
radiofrequency ablation, cryoablation, irreversible electroporation)
- Patient with symptomatic central nervous system (CNS) brain metastases, craniospinal
metastases, uncontrolled seizure disorder, or active neurological disease. Patients
presenting with brain metastases must be asymptomatic or treated and stable off
steroids and anti-convulsants for at least 1 month prior to study treatment
- Patient with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen
- Contraindication to enhanced magnetic resonance imaging (MRI) or computerized
tomography (CT) imaging (according to patient characteristics and investigator
decision)
- Absolute contraindication or known untreatable allergic reactions to contrast media
agents
- History of allogenic organ transplantation
- Known active infection including tuberculosis (clinical evaluation that includes
clinical history, physical examination and radiographic findings, and tuberculosis
(TB) testing in line with local practice), hepatitis B (known positive hepatitis B
[HBV] surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
(positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if
polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
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