Phase-I Trial of Pembrolizumab and Percutaneous Cryoablation Combination Followed by Nephron-Sparing Surgery or Cytoreductive Nephrectomy in Locally Advanced and Metastatic Renal Cell Carcinomas

NCT03189186 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2016-2961
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients will undergo a screening process as per standard of care to identify disease type and severity. Careful history and physical examination will also take place to rule out major heart, lung, or kidney disease and pregnancy that may affect how they will respond to the treatment. Patients with advanced (stage II and above with multiple tumors or tumors within vessels) and metastatic Renal Cell Carcinoma will be first treated with cryoablation on a large primary tumor and then given 200 mg pembrolizumab every 3-weeks 3 cycles , followed by partial/radical nephrectomy. Pembrolizumab is a biologic drug that adheres to the cell death receptors on white blood cells preventing there death and leading to an increased immunologic response. Cryoablation will be used in these patients to initially trigger and immune response to cancerous cells that is then magnified by the drug. After the surgery, patients will resume pembrolizumab for additional 5 cycles or up to a total of 2 years if a partial response is observed at the discretion of the treating medical oncologist or urologist until complete tumor remission, disease progression, unacceptable toxicity, patient refusal, or patient death due to any cause.

Conditions

Renal Cell Carcinoma; Metastatic Kidney Cancer

Keywords

Kidney Cancer; Immunotherapy; Renal Cell Carcinoma; Cryoablation; Metastatic Renal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Tumor responses to pembrolizumab and cryoablation combination followed by partial, radical or cytoreductive nephrectomy on secondary lesions. The tumor responses will be defined by CT images according to RECIST version 1.1., and reviewed by an experienced oncologist. The primary endpoint will be percentage of patients who achieve a best ORR, including both partial and complete responses.

  24 weeks after cryoablation

Secondary Outcomes (2)

• Progression-free Survival

  Follow-up will be for 24 months

• Overall Survival

  Follow-up will be for 24 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Advanced (stage II and above with multiple tumors or vena cava) and metastatic Renal Cell Carcinoma will be first treated with cryoablation on a large primary tumor and then given 200 mg pembrolizumab every 3-week for 3 cycles, followed by cytoreductive or partial/radical nephrectomy. After the surgery, patients will resume pembrolizumab for additional 5 cycles or up to a total of 2 years if a partial response is observed at the discretion of the treating medical oncologist or urologist until a complete tumor remission, disease progression, unacceptable toxicity, subject refusal, or subject death due to any cause.

Drug: Pembrolizumab Injection [Keytruda]; Procedure: Cryoablation; Procedure: Nephrectomy

Interventions

Pembrolizumab Injection [Keytruda] DRUG

Same as arm description

Also known as: Pembrolizumab

Pembrolizumab

Cryoablation PROCEDURE

Cryoablation uses liquid argon in metal needles to freeze tumors. Tumor cells are ruptured due to the forming ice crystals and die. Cryoablation is standardly used in tumors less then 4cm in diameter.

Pembrolizumab

Nephrectomy PROCEDURE

Nephrectomy is the surgical excision of either the entire kidney or a small portion of the kidney. Nephrectomy is standardly used to treat renal cell cancer.

Also known as: Partial Nephrectomy, Radical Nephrectomy, Nephron Sparring Surgery

Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be \>18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in days of treatment initiation.
• All screening labs should be performed within 10 days of treatment initiation.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

UC Irvine Health Department of Urology

Orange, California, 92868, United States

Location

Related Publications (10)

• Hruby GW, Fine JK, Landman J. Ultrasound-guided percutaneous ablation of a renal mass in a renal allograft. Urology. 2006 Oct;68(4):891.e5-6. doi: 10.1016/j.urology.2006.05.019.

  PMID: 17070386 BACKGROUND

• Ames CD, Vanlangendonck R, Venkatesh R, Gonzales FC, Quayle S, Yan Y, Humphrey PA, Landman J. Enhanced renal parenchymal cryoablation with novel 17-gauge cryoprobes. Urology. 2004 Jul;64(1):173-5. doi: 10.1016/j.urology.2004.02.033.

  PMID: 15245965 BACKGROUND

• Okhunov Z, Juncal S, Ordon M, George AK, Lusch A, del Junco M, Nguyentat M, Lobko II, Kavoussi L, Landman J. Comparison of outcomes in patients undergoing percutaneous renal cryoablation with sedation vs general anesthesia. Urology. 2015 Jan;85(1):130-4. doi: 10.1016/j.urology.2014.09.013. Epub 2014 Nov 14.

  PMID: 25440762 BACKGROUND

• Lusch A, Graversen JA, Liss MA, Landman J. Ablative techniques: Radiofrequency and cryotherapy, which is the best? Arch Esp Urol. 2013 Jan-Feb;66(1):71-8.

  PMID: 23406802 BACKGROUND

• Waitz R, Solomon SB, Petre EN, Trumble AE, Fasso M, Norton L, Allison JP. Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy. Cancer Res. 2012 Jan 15;72(2):430-9. doi: 10.1158/0008-5472.CAN-11-1782. Epub 2011 Nov 22.

  PMID: 22108823 BACKGROUND

• Zeng Z, Shi F, Zhou L, Zhang MN, Chen Y, Chang XJ, Lu YY, Bai WL, Qu JH, Wang CP, Wang H, Lou M, Wang FS, Lv JY, Yang YP. Upregulation of circulating PD-L1/PD-1 is associated with poor post-cryoablation prognosis in patients with HBV-related hepatocellular carcinoma. PLoS One. 2011;6(9):e23621. doi: 10.1371/journal.pone.0023621. Epub 2011 Sep 1.

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• Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013 Jul 11;369(2):134-44. doi: 10.1056/NEJMoa1305133. Epub 2013 Jun 2.

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• Zeelenberg IS, van Maren WW, Boissonnas A, Van Hout-Kuijer MA, Den Brok MH, Wagenaars JA, van der Schaaf A, Jansen EJ, Amigorena S, Thery C, Figdor CG, Adema GJ. Antigen localization controls T cell-mediated tumor immunity. J Immunol. 2011 Aug 1;187(3):1281-8. doi: 10.4049/jimmunol.1003905. Epub 2011 Jun 24.

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  PMID: 25944692 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

pembrolizumab; Cryosurgery; Nephrectomy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures

Study Officials

• Jaime Landman, MD

  UC Irvie Department of Urology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a longitudinal single armed open-label trial for advanced (stage II and above with multiple tumors or vena cava) and metastatic Renal Cell Carcinoma.

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 16, 2017
• Study Start: July 1, 2017
• Primary Completion: October 17, 2018
• Study Completion: October 17, 2018
• Last Updated: April 5, 2021

Record last verified: 2021-04

Locations

US (1)