Neoadjuvant Nivolumab for Upper Tract Urothelial Carcinoma

NCT05160285 | Unknown Phase 2 DMC

• 2 other identifiers: KCGMHCTC-2019005CPRPG8J0011
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to explore efficacy and safety of neoadjuvant nivolumab for non-metastatic upper tract urothelial carcinoma (UTUC), and explore the potential predictive biomarkers of immunotherapy.

Conditions

Upper Urinary Tract Urothelial Carcinoma

Keywords

upper tract urothelial carcinoma; immune checkpoint inhibitor; neoadjuvant treatment; pathological complete response; whole exome sequencing; biomarker; RNA sequencing; ctDNA

Outcome Measures

Primary Outcomes (1)

• pathologic complete response rate (pCR)

  determined by genitourologic pathologist

  1 month post neoadjuvant nivolumab and surgery

Secondary Outcomes (5)

• Treatment related adverse effect

  3 months during nivolumab treatment

• Surgical complication

  1 month within surgery

• Objective response rate

  3 months

• Disease free survival

  6 months

• Overall survival

  6 months

Study Arms (1)

Neoadjuvant nivolumab treatment arm

EXPERIMENTAL

Nivolumab 360mg intravenous adminstration every 3 weeks

Drug: Nivolumab 100 MG in 10 ML Injection

Interventions

Nivolumab 100 MG in 10 ML Injection DRUG

If you meet all the conditions to participate in the trial, you will receive the following treatments: Your physician will give you 360 mg of Nivolumab as an intravenous infusion every 3 weeks for about 30 minutes. For safety reasons, we recommend that you stay in the hospital for 60 minutes after the initial infusion of nivolumab. There will be a total of 3 cycles of Nivolumab treatments during the study period. You will need to return every 3 weeks. Each return will collect about 50 ml (10 tsp) of blood samples, depending on local standards.

Neoadjuvant nivolumab treatment arm

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically or clinically confirmed diagnosis of locally advanced (cT2-T4 and N0M0) urothelial carcinoma of the renal pelvis and/or ureter (UTUC). Pure urothelial carcinoma or urothelial carcinoma mixed with other histological variant are allowed, but urothelial carcinoma must be the predominant histology.
• Have at least a measurable lesion based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
• Voluntarily agree to participate by providing written informed consent/assent for the trial.
• Age (at the time of informed consent): 20 years and older
• Have received no prior systemic chemotherapy for advanced urothelial carcinoma, with the following exceptions:
• Platinum-based chemotherapy for previous a history of ipsilateral UTUC or bladder cancer in purpose of neoadjuvant or adjuvant treatment with recurrence \> 6 months from completion of therapy is permitted.
• Low-dose chemotherapy (e.g., low-dose cisplatin, cisplatin plus 5-FU, mitomycin plus 5-FU, or cisplatin plus paclitaxel) given concurrently with radiation to urothelial carcinoma of bladder is not considered systemic therapy.
• Have willing to provide tissue for exploratory biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion from the renal pelvis or ureter tumor.
• Have an ECOG PS of 0, 1, or 2.
• Have adequate organ function as defined in Table 6. (All screening labs should be performed within 3 weeks prior to treatment initiation.)
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial 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 must be willing to use an adequate method of contraception as outlined in Section 7.5.2 - Contraception, for the course of the trial through 5 months or more after the last dose of nivolumab

You may not qualify if:

• \. Is currently participating and receiving study therapy or investigational agents. Patients who withdraw of previous clinical trials should have a 4-weeks washout period of investigational drug before participating this study.
• \. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
• \. Has an 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Short-term (\<7 days) use of systemic corticosteroids is allowed when use is considered SOC.
• Subjects with vitiligo, type I diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy would be an exception to this rule.
• Subjects who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the trial.
• \. Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.
• <!-- -->
• Exceptions include basal cell carcinoma of the skin; squamous cell carcinoma of the skin that has undergone potentially curative surgery; in situ cervical cancer; early stage of prostate cancer (stage 1) with low Gleason score ≤6; and prostate-specific antigen (PSA) undetectable.
• A history of urothelial carcinoma, including upper tract urothelial carcinoma or bladder cancer who received curative-intent surgery (nephroureterectomy, segmentectomy, TURBT, partial cystectomy, radical cystoprostectomy) \> 12 months before first-dose trial treatment will be the exception.
• \. Has a history of (non-infectious) pneumonitis or interstitial lung disease or pulmonary fibrosis diagnosed based on imaging (CT of chest preferably).
• \. Has active tuberculosis (TB) (Bacillus tuberculosis). 7. Has an active infection requiring systemic therapy within 7 days prior to the first dose of trial treatment.
• \. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 5 months or more after the last dose of nivolumab.
• \. Has a history of uncontrolled or significant cardiovascular disease meeting any of the following:
• <!-- -->

Sponsors & Collaborators

• YULISU: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (1)

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 833, Taiwan

RECRUITING

MeSH Terms

Interventions

Nivolumab; Injections

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yu-Li Su, MD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu-Li Su, MD

CONTACT

+886-975056834; yolisu@cgmh.org.tw

Chien-Ya Lin, RPN

CONTACT

+886-7-7317123; chanyai0725@cgmh.org.tw

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor-level Attending Physician

Model Details: Open Label, Single-arm, Phase II Study

Study Record Dates

• First Submitted: December 24, 2020
• First Posted: December 16, 2021
• Study Start: December 25, 2020
• Primary Completion: December 15, 2023
• Study Completion: December 30, 2024
• Last Updated: December 16, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)