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Clear Cell Renal Cell CarcinomaEarly Phase 1NCT02626130

Tremelimumab With or Without Cryoablation in Treating Patients With Metastatic Kidney Cancer

A Early Phase 1 study testing Cryosurgery, Laboratory Biomarker Analysis and Therapeutic Conventional Surgery in people with Clear Cell Renal Cell Carcinoma and Metastatic Renal Cell Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This randomized pilot clinical trial studies the side effects of tremelimumab with or without tissue cryoablation in treating patients with kidney cancer that has spread to other places in the body. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cryosurgery, Laboratory Biomarker Analysis and Therapeutic Conventional Surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
30 Mar 2016to 20 Jun 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • Metastatic renal cell carcinoma (clear cell or non clear cell)
  • One metastatic site amenable to cryoablation
  • Patients with a single metastatic site may be enrolled if that site is amenable to ablation; however these patients will not be counted in secondary measures of response unless there is new disease detected during follow up
  • Eligible for cytoreductive nephrectomy, metastasectomy, or repeated biopsy; biopsy site cannot be lung, mediastinal lymph node, or bone (unless soft tissue component)
  • Patients with any number of prior therapies with anti-angiogenic agents or immunotherapy with the exception of any previous anti-CTLA-4 directed agents are allowed; a 2 week washout period is required for all agents, except for bevacizumab where a 4 week washout is required
  • Performance status with Eastern Cooperative Oncology Group (ECOG) score =< 2; patients with performance status of 3 may be considered as long as the decline has been of short duration (< 1 month), and is due to their malignancy and not a comorbid condition (example: pain limiting activity)
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  • Patient's with an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC or Heng) score of 3 or less will be included; score greater than 4 will be excluded; 1 point each: requirement of systemic treatment for metastatic disease less than 1 year of original diagnosis of renal cell carcinoma, a serum calcium greater than 10, anemia, neutrophilia, thrombocytosis, ECOG performance status >= 2
  • No history of autoimmune disorders
  • White blood cell (WBC) >= 2000/uL
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets >= 75 x 10^3/uL
  • Hemoglobin >= 9 g/dL
  • Creatinine =< 3 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) =< 3.0 x ULN for patients without liver metastases; for patients with liver metastasis ALT =< 5 x ULN is allowed
  • Bilirubin =< 1.5 x ULN (except for patients with Gilbert's syndrome, who must have a total bilirubin =< 3 mg/dL)
  • Ability to understand and willingness to sign a written informed consent document
  • Females of childbearing potential who are sexually active with a non-sterilized male partner and non-sterilized males must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 180 days after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician; periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception; they must also refrain from egg cell donation for 180 days after the final dose of investigational product; females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause); a highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly; the acceptable methods of contraception are: barrier method (e.g. male condom with spermicide, copper T intrauterine device, or levonorgestrel-releasing intrauterine system - Mirena) or hormonal methods (e.g. implants, hormone shot or injection, combined pill, minipill, or patch)

Who cannot join

  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03 grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria
  • Known or suspected autoimmune disease; patients with a history of 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; patients with a history of Hashimoto's thyroiditis only requiring hormone replacement, type I diabetes, or psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed to participate
  • Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug; inhaled steroids and adrenal replacement steroids doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Autoimmune disease: patients with a history of 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
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
  • Patients with untreated brain metastases
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  • Major surgery within 4 weeks of enrollment
  • History of other malignancies, other than non-melanoma skin cancer, Ta or T1 (low grade) bladder carcinomas, or other low grade cancer of very low clinical impact, unless in complete remission and off therapy for that disease for at least 2 years
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Untreated symptomatic spinal cord compressions
  • Any non-oncology live or attenuated vaccine therapy used for prevention of infectious diseases within 30 days prior to the first dose of tremelimumab; if patients is enrolled, patient should not receive live vaccine during the study and 180 days after the last dose of tremelimumab
  • Concomitant therapy with any of the following: interleukin 2 (IL-2), interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses)
  • Previous participation in tremelimumab or ipilimumab clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist
  • Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control from screening to 90 days after the last dose of tremelimumab monotherapy

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: A Pilot Study of Tremelimumab With or Without Tissue Cryoablation in Patients With Metastatic Renal Cell Carcinoma

This randomized pilot clinical trial studies the side effects of tremelimumab with or without tissue cryoablation in treating patients with kidney cancer that has spread to other places in the body. Tremelimumab binds to a protein called cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which is found on the surface of T cells (a type of white blood cell). Tremelimumab may block CTLA-4 and help the immune system kill cancer cells. Cryoablation is a procedure that uses a hollow, thin tube called a cryoprobe to freeze and destroy cancer tissue. It is not yet known whether tremelimumab with or without cryoablation is effective in treating patients with kidney cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate safety of tremelimumab alone and in combination with cryoablation in patients with metastatic renal cell carcinoma (RCC).

SECONDARY OBJECTIVES:

  1. To explore the longitudinal values for immunological variables (including cluster of differentiation [CD]4+ ICOS+ T cells; effector to regulatory T cell ratio; absolute lymphocyte count) following treatment with tremelimumab in patients with metastatic RCC, and evaluate difference between combination cryoablation and tremelimumab in comparison to tremelimumab alone.

II. To determine the objective response rate and progression-free survival of patients treated with tremelimumab with or without cryoablation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive tremelimumab intravenously (IV) over 60 minutes at weeks 1 and 5. Within 4-6 weeks later, patients undergo surgery or biopsy. After surgery or biopsy, patients receive tremelimumab IV every 4 weeks (Q4W) for 3 doses, and then every 12 weeks (Q12W) in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo cryoablation and receive tremelimumab IV over 60 minutes at weeks 1 (2-6 days after cryoablation) and 5. Within 4-6 weeks later, patients undergo surgery or biopsy. After surgery or biopsy, patients receive tremelimumab IV Q4W for 3 doses, and then Q12W in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, and 90 days, and then every 6 months.

Being tested
Cryosurgery, Laboratory Biomarker Analysis, Therapeutic Conventional Surgery, Tremelimumab
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • CryosurgeryProcedure or surgery

    Also called cryoablation, cryosurgical ablation

    Undergo cryoablation

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgery

  • TremelimumabBiological

    Also called Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206

    Given IV

Study groups in NCT02626130
Study groupRoleWhat they receive
Arm A (tremelimumab)ExperimentalPatients receive tremelimumab IV over 60 minutes at weeks 1 and 5. Within 4-6 weeks later, patients undergo surgery or biopsy. After surgery or biopsy, patients receive tremelimumab IV Q4W for 3 doses, and then every Q12W in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery; Biological: Tremelimumab
Arm B (tremelimumab and cryoablation)ExperimentalPatients undergo cryoablation and receive tremelimumab IV over 60 minutes at weeks 1 (2-6 days after cryoablation) and 5. Within 4-6 weeks later, patients undergo surgery or biopsy. After surgery or biopsy, patients receive tremelimumab IV Q34W for 3 doses, and then Q12W in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Cryosurgery; Other: Laboratory Biomarker Analysis; Procedure: Therapeutic Conventional Surgery; Biological: Tremelimumab

What is being measured

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

  1. Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

    Safety will be recorded through the incidence of adverse events, serious adverse events and specific laboratory abnormalities (worst grade) in each treatment arm. Descriptive statistical analyses will be performed to summarize the incidence of adverse events.

    Measured: Up to 2 weeks

  2. Incidence of extreme toxicities as graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03

    Extreme toxicities will be defined as any grade 3 or higher adverse event that is possibly, probably, or definitely related to therapy that occurs within the first two cycles of therapy with the following exceptions: any grade 3 or higher adverse event that is potentially treatable with steroids will only count as an extreme toxicity if it does not improve to grade 1 or better within 2 weeks of steroid therapy, grade 3 or 4 amylase or lipase abnormalities that are not associated with symptoms or clinical manifestations of pancreatitis, or grade 3 or 4 drug related endocrinopathies which within two weeks of presentation are adequately controlled with only physiologic hormone replacement therapy.

    Measured: Up to 2 weeks

Secondary outcomes (4)

  1. Response rate

    Descriptive statistical analyses will be performed to summarize the response rate including summary tables, scatter-plots, box-plots, proportions, 95% credible intervals, median, means, and standard deviations.

    Measured: Up to 5 years

  2. Changes in indication markers

    Differences of indication markers between arms will be compared using a t-test with transformations of non-normal data, as needed. A mixed model accounting for patient effects will be used to analyze the longitudinal data on immunological values over time.

    Measured: Up to 5 years

  3. Progression free survival

    Descriptive statistical analyses will be performed.

    Measured: Up to 5 years

  4. Longitudinal data on immunological values over time

    A mixed model accounting for patient effects will be used to analyze the longitudinal data on immunological values over time.

    Measured: Up to 13 weeks

Timeline

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

  1. First posted10 Dec 2015 (estimated)
  2. Study start30 Mar 2016
  3. Primary completion20 Jun 2022
  4. Study completion20 Jun 2022

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
Early Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02626130
Sponsor's protocol ID
2013-0539
Other IDs
NCI-2016-00008, 2013-0539
Status last verified
Jul 2022
First submitted
4 Dec 2015
Last updated
7 Jul 2022
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Campbell MT, Matin SF, Tam AL, Sheth RA, Ahrar K, Tidwell RS, Rao P, Karam JA, Wood CG, Tannir NM, Jonasch E, Gao J, Zurita AJ, Shah AY, Jindal S, Duan F, Basu S, Chen H, Espejo AB, Allison JP, Yadav SS, Sharma P. Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma. Nat Commun. 2021 Nov 4;12(1):6375. doi: 10.1038/s41467-021-26415-4.

    PubMed 34737281

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Cryosurgery, Laboratory Biomarker Analysis and Therapeutic Conventional Surgery in people with Clear Cell Renal Cell Carcinoma and Metastatic Renal Cell Cancer, 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 17 inclusion and 15 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: finished, as of the sponsor's last update on 7 Jul 2022. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (time frame: Up to 2 weeks). The study lists 2 primary outcomes in all. 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 NCT02626130, which also lists 1 linked publication.

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 7 Jul 2022.

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