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Metastatic Malignant NeoplasmNCT04150939

Cryoablation for the Treatment of Metastatic Cancer

A study testing Core Biopsy, Cryosurgery and Immunotherapeutic Agent in people with Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This interventional trial studies the effectiveness of adding cryoablation treatment in patients who are receiving standard of care immunotherapy to treat cancer that is has spread to other parts of the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Malignant Neoplasm
What is being tested?
Core Biopsy, Cryosurgery and Immunotherapeutic Agent
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
23 Dec 2019to 31 Aug 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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])
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Cryoablation Challenge Evaluated in Adaptive-Immune Resistance (CEDAR)

This interventional trial studies the effectiveness of adding cryoablation treatment in patients who are receiving standard of care immunotherapy to treat cancer that is has spread to other parts of the body (metastatic). Cryoablation uses a probe that freezes the tissue around the tumor to try to kill the cancer cells. Using cryoablation to treat cancerous lesions may help to kill the cancer cells.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the effect of cryoablation on adaptive resistance to immunotherapy in metastatic cancer patients.

SECONDARY OBJECTIVES:

  1. To assess additional efficacy response to treatment. II. To assess the safety and tolerability of cryoablation in this population. III. To compare the radiologic response of ablated and non-ablated lesions using Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1.

IV. To assess the immune effect of cryoablation on the non-ablated lesion using pre- and post-treatment biopsies.

EXPLORATORY OBJECTIVE:

  1. To evaluate the immune microenvironment and systemic changes as a result of cryoablation with the goal of biomarker discovery.

OUTLINE:

Beginning 1 week prior to the next scheduled standard of care immunotherapy infusion, patients undergo core biopsy of the lesion to be ablated and a non-ablated lesion and also undergo cryoablation. Patients undergo a mandatory second core biopsy of the non-ablated lesion at 4 weeks after cryoablation.

After completion of study, patients are followed up for 12 months after cryoablation and then periodically thereafter.

Being tested
Core Biopsy, Cryosurgery, Immunotherapeutic Agent
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Core BiopsyProcedure or surgery

    Also called core needle biopsy

    Undergo core biospy

  • CryosurgeryProcedure or surgery

    Also called Cryoablation, cryosurgical ablation

    Undergo cryoablation

  • Immunotherapeutic AgentDrug

    Also called Biological Response Modifier, Biomodulators, BRM, Immune Mediators

    Receive standard of care immunotherapy

Study groups in NCT04150939
Study groupRoleWhat they receive
Treatment (cryoablation)ExperimentalBeginning 1 week prior to the next scheduled standard of care immunotherapy infusion, patients undergo core biopsy of the lesion to be ablated and a non-ablated lesion and also undergo cryoablation. Patients undergo a mandatory second core biopsy of the non-ablated lesion at 4 weeks after cryoablation.
Receives: Procedure: Core Biopsy; Procedure: Cryosurgery; Drug: Immunotherapeutic Agent

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best objective response (complete response or partial response)

    Will be determined by Immune-Modified Response Evaluation Criteria in Solid Tumors (iRECIST). Best objective response will be measured by the proportion of patients who achieve complete response (CR) + partial response (PR). The proportion of patients in the efficacy evaluable population who respond (i.e., have a best response of CR or PR) will be estimated along with the corresponding 95% confidence interval, using the Clopper-Pearson exact method.

    Measured: Up to 12 months post cryoablation

Secondary outcomes (9)

  1. Progression free survival (PFS)

    Will be determined by iRECIST. PFS will be calculated and plotted by Kaplan-Meier methods.

    Measured: Up to 2 years

  2. Time to progression (TTP)

    Will be determined by iRECIST. TTP will be calculated and plotted by Kaplan-Meier methods

    Measured: Up to 2 years

  3. Time to progression on a ablated versus non-ablated basis

    Ablated lesions time to progression will be determined b iRECIST and RECIST 1.1. Non-ablated lesion time to progression will be determined by iRECIST and RECIST 1.1. TTP will be calculated and plotted by Kaplan-Meier methods.

    Measured: Up to 2 years

  4. Disease control rate (CR + PR + stable disease [SD])

    Descriptive statistics will summarize disease control rate by iRECIST.

    Measured: Up to 2 years

  5. Duration of stable disease

    Descriptive statistics will summarize duration of stable disease by iRECIST.

    Measured: Up to 2 years

  6. Duration of response

    Descriptive statistics will summarize duration of response by iRECIST.

    Measured: Up to 2 years

  7. Incidence of adverse events (AEs)

    AEs will be graded and categorized according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Counts and percentages of patients experiencing each adverse event as well as any grade 3 or higher event will be summarized.

    Measured: Up to 2 years

  8. Overall survival (OS)

    OS will be calculated and plotted by Kaplan-Meier methods.

    Measured: From the date of study entry until death from any cause, assessed up to 2 years

  9. Changes in T-effector cell populations

    Will use a paired t test to determine if there is a difference in pre- and post immune cryoablation therapy in T-effector cell populations; T-regulatory populations; CD4 subsets; B cell populations; dendritic and macrophage populations. Will use scatterplots to demonstrate correlation between immunologic markers obtained in peripheral blood versus those obtained at the tissue level. A Pearson correlation will be estimated to describe the level of association.

    Measured: Baseline up to 12 months post cryoablation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2019
  2. Study start23 Dec 2019
  3. Primary completion31 Aug 2028 (estimated)
  4. Study completion31 Aug 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04150939
Sponsor's protocol ID
2019-0502
Other IDs
NCI-2019-07100, 2019-0502
Status last verified
Aug 2026
First submitted
1 Nov 2019
Last updated
6 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes

Questions about this trial

What is this clinical trial studying?

A study testing Core Biopsy, Cryosurgery and Immunotherapeutic Agent in people with Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best objective response (complete response or partial response) (time frame: Up to 12 months post cryoablation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04150939.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.

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