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Bladder CancerPhase 2NCT03558087

Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

A Phase 2 study testing Nivolumab, Gemcitabine and Cisplatin in people with Bladder Cancer, run by Matthew Galsky at 7 sites 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 is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Nivolumab, Gemcitabine and Cisplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
7 sitesUnited States
Study dates
13 Jul 2018to 7 Mar 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • ECOG Performance Status of ≤ 1 within 28 days prior to registration.
  • Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder (i.e., ct2-4n0m0). candidate for cystectomy as per treating physician.
  • Demonstrate adequate organ function per listed criteria:
  • Absolute Neutrophil Count (ANC): ≥ 1.5 x 10^9/L
  • Hemoglobin (Hgb): ≥ 9 g/dL
  • Platelets: ≥ 100 x 10^9/L
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  • Calculated creatinine clearance: Creatinine ≤ 1.5 or creatinine clearance ≥ 60 mL/min
  • Bilirubin: ≤ 1.5 × upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) : ≤ 3 × ULN
  • Alanine aminotransferase (ALT) : ≤ 3 × ULN
  • All subjects must have adequate archival tissue identified at screening (i.e., at least 15 unstained slides or paraffin block). Subjects without available archival tissue must be discussed with the sponsor-investigator.
  • Women of childbearing potential must have a negative serum or urine pregnancy within 7 days prior to C1D1. NOTE: "Women of childbearing potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 62 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
  • NOTE: Women of childbearing potential (WOCBP) receiving nivolumab must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent to 5 months after the last dose of nivolumab or for the timeframe outlined per package insert for chemotherapy. This timeframe also applies to breastfeeding. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method. Male subjects capable of fathering a child that are sexually active with partners of childbearing potential must be willing to abstain from heterosexual intercourse or to use 2 forms of effective methods of contraception from the time of informed consent to the timeframe outlined per package insert for chemotherapy. Contraception is not required for nivolumab. The timeframes described in the previous 2 sentences apply to sperm donation. Two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.

Who cannot join

  • Prior treatment with systemic chemotherapy for muscle-invasive urothelial cancer of the bladder
  • Active infection requiring systemic therapy
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
  • Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
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  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Grade ≥ 2 neuropathy (NCI CTCAE version 4).
  • Prior radiation therapy for bladder cancer
  • Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody (HCV antibody) indicating acute or chronic infection.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Solid organ or allogeneic stem cell transplant

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • City of Hope

    Duarte, California, 91010

  • Univerity of Southern California

    Los Angeles, California, 90033

  • University of Wisconsin

    Madison, Wisconsin, 53705

  • Icahn School of Medicine: Tisch Cancer Institute at Mount Sinai Medical Center

    New York, New York, 10029

  • Penn Medicine Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Huntsman Cancer Institute University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: Neoadjuvant Gemcitabine, Cisplatin, Plus Nivolumab in Patients With Muscle-invasive Bladder Cancer With Selective Bladder Sparing

This is a phase 2 trial seeking to define the safety and activity of gemcitabine, cisplatin, plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to define the role of clinical complete response in predicting benefit in patients opting to avoid cystectomy.

Conditions
Bladder Cancer
Keywords
muscle-invasive
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

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

  • NivolumabDrug

    Also called Opdivo

    Nivolumab 360mg will be administered on Day 1 of each 21 day cycle for four 21-day cycles. Based on response and a balanced patient-physician discussion, subjects may receive nivolumab 240 mg for 8 cycles (cycle = 14 days).

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine 1000mg/m^2 will be administered on Days 1 and 8 for four 21-day cycles.

  • CisplatinDrug

    Also called Platinol

    Cisplatin 70mg^m2 will be administered on Day 1 for four 21-day cycles.

Study groups in NCT03558087
Study groupRoleWhat they receive
Gemcitabine, Cisplatin and NivolumabExperimentalCombination Therapy: Nivolumab 360mg IV, Gemcitabine 100mg/m^2 IV ,Cisplatin 70mg/m^2 IV for four 21-day cycles. At restaging, subjects with cT0 or cTa status may undergo cystectomy or continue maintenance Nivolumab 240mg IV for up to 8 14-day cycles. Subjects with > cTa status will undergo cystectomy.
Receives: Drug: Nivolumab; Drug: Gemcitabine; Drug: Cisplatin

What is being measured

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

  1. Clinical Complete Response (CCR) Rate

    Clinical complete response rate will be defined as the percentage of patients who achieved cT0 or cTa disease after gemcitabine, cisplatin, plus nivolumab.

    Measured: 24 months

  2. Predict Benefit From Treatment

    Determine the ability of clinical complete response (cT0 or cTa) to predict benefit from treatment.Benefit will be defined as a pathologic complete response (<pT1) in patients undergoing cystectomy and 2 year metastasis-free in patients pursuing surveillance.

    The positive predictive value of CCR with 95% confidence interval are presented in Outcome Measure Data Table. Positive predictive value is the ratio of patients truly diagnosed as positive to all those who had positive test results.

    Measured: 24 months

Secondary outcomes (6)

  1. Adverse Events

    The frequency and severity of all grade 3+ treatment-emergent adverse events occurring in at least 10% of patients are reported by CTCAEv4 term and grade.

    Measured: AE had been recorded from time of signed informed consent until 100 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 13 months.

  2. Bladder Intact Overall Survival

    Bladder-intact overall survival is defined as the time from initiation of treatment until death or cystectomy.

    Measured: Up to a maximum of 60 months

  3. Recurrence-free Survival

    Recurrence-free survival is defined as the time from initiation of treatment to death or recurrence, depending on which occurs first

    Measured: Up to a maximum of 60 months

  4. Pathologic Complete Response Rate in Patients Undergoing Cystectomy

    Pathologic complete response rate in patients undergoing radical cystectomy is defined as the proportion of patients with <pT1

    Measured: Up to a maximum of 53 months

  5. Association Between a Prespecified Panel of Genomic Biomarkers and Benefit From Treatment in Patients Achieving a Clinical Complete Response.

    Benefit will be defined as a pathologic complete response (p<T1) in patients undergoing cystectomy and 2 years metastasis-free in patients pursuing surveillance.

    The positive predictive value of CCR with or without genomic alterations in baseline TURBT tissue for a composite outcome measure of 2-year bladder-intact survival in patients forgoing immediate cystectomy or <ypT1N0 in patients undergoing immediate cystectomy are presented with 95% confidence interval in Outcome Measure Data Table.

    Positive predictive value is the ratio of patients truly diagnosed as positive to all those who had positive test results.

    Measured: 24 months

  6. Overall Survival

    Overall survival is defined as the time from initiation of treatment to death.

    Measured: Up to a maximum of 60 months

Timeline

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

  1. First posted15 Jun 2018
  2. Study start13 Jul 2018
  3. Primary completion16 Feb 2024
  4. Study completion7 Mar 2024

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
76 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03558087
Sponsor's protocol ID
HCRN GU16-257
Status last verified
May 2024
First submitted
5 Jun 2018
Last updated
27 Jun 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Gemcitabine and Cisplatin in people with Bladder Cancer, run by Matthew Galsky at 7 sites 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 13 inclusion and 14 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 27 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites 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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Clinical Complete Response (CCR) Rate (time frame: 24 months). 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 NCT03558087.

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 27 Jun 2024; AzTrials last refreshed its copy on 8 Nov 2026.

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