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Urothelial CarcinomaPhase 2NCT03179943

Atezolizumab + Guadecitabine in Patients With Checkpoint Inhibitor Refractory or Resistant Urothelial Carcinoma

A Phase 2 study testing Atezolizumab and Guadecitabine in people with Urothelial Carcinoma, run by Fox Chase Cancer Center at 3 sites 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 is a single arm Phase II study with a safety run-in to identify the recommended phase II dose of the combination therapy of atezolizumab and guadecitabine. Patients with recurrent/advanced urothelial carcinoma (stage IV) who had previously progressed on check-point inhibitor therapy with PD-1 or PD-L1 targeting… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
Atezolizumab and Guadecitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
3 sitesUnited States
Study dates
27 Nov 2017to Jul 2022
Phase
Phase 2
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

  • Patients must have histologically confirmed urothelial carcinoma that is advanced or metastatic.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v. 1.1 and ≥ 1 site safe for biopsy.
  • Patient must agree to provide fresh biopsy specimens and peripheral blood samples at the time of screening and during the study.
  • Patients must have received or be ineligible for platinum based chemotherapy and must have received at least one line of therapy with a PD-L1 or PD-1 targeting agent.
  • Age > 18 years.
  • ECOG performance status ≤ 2
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  • Life expectancy ≥ 12 weeks
  • Patients must have normal organ and marrow function as defined below
  • Leukocytes > 3,000/mcL
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Hemoglobin > 9 g/dl (blood transfusion is allowed to meet the eligibility criteria as long as post transfusion hemoglobin is maintained at ≥9.0 g/dL for 7 days or longer)
  • Total bilirubin ≤ 2.5 x institutional upper limit of normal (ULN).
  • AST/ALT (SGOT/SGPT) < 2.5 times institutional normal limits unless liver metastases are present in which case AST and ALT must be ≤ 5 x IULN.
  • Creatinine within normal institutional limits OR
  • Creatinine clearance > 30 Ml/min (Cockcroft-Gault formula or measured with 24h urine)
  • INR or PTT/PT ≤ 1.5 ULN unless patient is on stable therapeutic dose of warfarin
  • Ability to understand and willingness to sign a written informed consent and HIPAA consent document
  • Women of child bearing potential and men must agree to remain abstinent or use adequate contraception (failure rate <1%) for the duration of study and for 90 days after the completion of the therapy.

Who cannot join

  • Patients who have had anti-cancer therapy within 2 weeks prior to entering the study.
  • Patients receiving any other investigational agents
  • Patients with active or untreated CNS disease. Patients previously treated for CNS disease must be asymptomatic and must not be using steroids for at least 4 weeks prior to starting the study treatment.
  • Patients with active auto-immune disease requiring immunosuppressive medication.
  • Patients treated with systemic immunostimulatory agents (such as interferons, IL 12) within 6 weeks of the start of the treatment or 5 half-lives of the drug, whichever is shorter.
  • Treatment with systemic corticosteroids within 2 weeks prior to the start of the treatment. Patients that require inhaled or low-dose corticosteroids for COPD or asthma, mineralocorticoids are allowed.
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  • Patients with active malignancies in addition to urothelial carcinoma.
  • Patients with prior treatment with hypomethylating agents.
  • History of leptomeningeal disease
  • Prior allogeneic stem cell or solid organ transplant.
  • Uncontrolled effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
  • Uncontrolled symptomatic hypercalcemia (>1.5mmol/L ionized calcium or calcium > 12mg/dl or corrected serum calcium > ULN)
  • Mean QT interval corrected for heart rate (QTc) ≥ 470ms calculated from 3 ECGs using Frediricia's correction.
  • Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 except for endocrine AEs managed with replacement therapy. Any other AEs unresolved toxicities grade 2 or more from previous anti-cancer therapy, except alopecia, peripheral neuropathy or non-clinically significant lab abnormalities.
  • Receipt of therapeutic oral or IV antibiotics within 2 weeks prior to the start of the study treatment.
  • Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
  • History of severe allergic, anaphylactic or hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterations), drug-induced pneumonitis or idiopathic pneumonitis or evidence of interstitial lung disease or active non-infectious pneumonitis.
  • Active tuberculosis
  • Known hypersensitivity to Chinese hamster ovary cell products or any of the study drugs.
  • Administration of a live, attenuated vaccine within 4 weeks of the start of treatment or anticipation that such a live, attenuated vaccine will be required during the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible.
  • Known history of HBV or HCV infection.
  • Pregnant or breast feeding.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21287

  • USC Norris Hospital and Clinics

    Los Angeles, California, 90033

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: GU-114: Overcoming Checkpoint Inhibitor Resistance With Epigenetic Therapy in Urothelial Cancer

This is a single arm Phase II study with a safety run-in to identify the recommended phase II dose of the combination therapy of atezolizumab and guadecitabine. Patients with recurrent/advanced urothelial carcinoma (stage IV) who had previously progressed on check-point inhibitor therapy with PD-1 or PD-L1 targeting agents are eligible for this study. After a dose that is safe and tolerable has been established, a dose expansion phase (Phase II) will begin. This study will enroll a total of 4 to 53 patients depending upon the number of patients treated in the safety run-in phase and the number of subjects replaced during the phase II portion.

Being tested
Atezolizumab, Guadecitabine
Keywords
bladder cancer, Ureteral Cancer, Urothelial cancer, Urethral cancer
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Ureteral Neoplasms, Urethral Neoplasms

What participants receive

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

  • AtezolizumabDrug

    Patients will be administered atezolizumab intravenously on day 1 and day 22 of a 6 week cycle for the period of 8 cycles.

  • GuadecitabineDrug

    Guadecitabine will be administered subcutaneously on days 1 through 5 of the 6 week cycle for the period of 4 cycles

Study groups in NCT03179943
Study groupRoleWhat they receive
Atezolizumab + GuadecitabineExperimentalNot described
Receives: Drug: Atezolizumab; Drug: Guadecitabine

What is being measured

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

  1. Maximum tolerated dose of Guadecitabine in combination of Atezolizumab in safety run-in phase

    Dose de-escalation study based on standard 3+3 design will be conducted to test two dose levels of guadecitabine: 45mg/m2 and 36mg/m2 to determine MTD

    Measured: 2-3 months

  2. Objective Response Rate (RECIST v 1.1) in Phase II

    Measured: 2 years

Secondary outcomes (2)

  1. Overall Survival

    Measured: 2 years

  2. Progression Free Survival

    Measured: 2 years

Timeline

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

  1. First posted7 Jun 2017
  2. Study start27 Nov 2017
  3. Primary completion12 Jul 2020
  4. Study completionJul 2022 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03179943
Sponsor's protocol ID
GU-114
Other IDs
SU2C-AACR-CT08-17
Status last verified
Nov 2021
First submitted
6 Jun 2017
Last updated
4 Nov 2021
Results posted
No
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 Atezolizumab and Guadecitabine in people with Urothelial Carcinoma, run by Fox Chase Cancer Center at 3 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 19 inclusion and 25 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 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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?

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?

Maximum tolerated dose of Guadecitabine in combination of Atezolizumab in safety run-in phase (time frame: 2-3 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 NCT03179943.

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 4 Nov 2021.

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