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Urothelial CarcinomaPhase 2NCT03737123

Trial of Atezolizumab Plus Chemotherapy After Progression on PD-1 or PD-L1 in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma

A Phase 2 study testing Carboplatin, Gemcitabine and Atezolizumab in people with Urothelial Carcinoma, run by Nabil Adra at 4 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a single arm phase II study assessing the activity of atezolizumab in combination with carboplatin + gemcitabine or docetaxel compared to historical controls of chemotherapy only in metastatic or recurrent urothelial carcinoma subjects. 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?
Carboplatin, Gemcitabine and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
4 sitesUnited States
Study dates
19 Dec 2018to 18 May 2022
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

  • Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • Age ≥ 18 years at the time of consent.
  • ECOG Performance Status of 0-2 within 28 days prior to registration.
  • Histological or cytological confirmed metastatic or unresectable locally advanced urothelial carcinoma (primary tumor: renal pelvis, ureters, urinary bladder, or urethra).
  • Patients with mixed histologies are eligible.
  • Cisplatin ineligible at the time of diagnosis with metastatic urothelial carcinoma based on consensus definition with any of the following criteria: ECOG PS 2, creatinine clearance < 60mL/min, CTCAE v4 grade ≥ 2 hearing loss, CTCAE v4 grade ≥ 2 peripheral neuropathy, New York Heart Association (NYHA) class ≥ 3 heart failure.
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  • Measurable disease according to RECIST 1.1 within 28 days prior to registration.
  • Must have had progressive metastatic disease after previous treatment with PD-1 or PD-L1 inhibitor (in the adjuvant or metastatic setting). Treatment regimen will be determined based on prior treatment:
  • PD1 or PDL1 inhibitor with no prior platinum chemotherapy for metastatic disease. These patients should be treated with atezolizumab + carboplatin + gemcitabine on trial.
  • Sequential or concurrent PD1/PDL1 inhibitor and carboplatin-based regimen. These patients should be treated with atezolizumab + docetaxel on trial.
  • Most recent therapy does not have to have been a checkpoint inhibitor. Intercurrent treatment is acceptable if subjects meet all other inclusion criteria.
  • A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study registration, have been off of corticosteroids for ≥ 2 weeks, and are asymptomatic.
  • Previous neoadjuvant or adjuvant chemotherapy that was completed 6 months prior to study enrollment is allowed.
  • REQUIRED archival tumor tissue (prior to treatment with single agent PD-1 or PD-L1 inhibitor) must be identified prior to registration and obtained during the screening period. Confirmation of acquisition should occur prior to C1D1 treatment. Unavailability of tissue will render the subject ineligible for study. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient. Sample requirement is FFPE block + 1 H\&E stained slide or 25 unstained slides + 1 H\&E stained slide.
  • Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 28 days prior to registration.
  • White blood cell (WBC) ≥ 2 k/mm3
  • Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
  • Hemoglobin (Hgb) ≥ 9 g/dL
  • Platelet >100k
  • Estimated creatinine clearance ≥ 30 mL/min
  • Bilirubin 1.5 ≤ (ULN)
  • Aspartate aminotransferase (AST) ≤ 1.5 × ULN
  • Alanine aminotransferase (ALT) ≤ 1.5 × ULN
  • International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤ 2 × ULN (Note: This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose)
  • Females of childbearing potential (FOCBP) must have a negative serum pregnancy test within 28 days prior to registration. These women must also have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of atezolizumab then every 6 weeks thereafter. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is post-menopausal. 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.
  • Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 150 days (5 months) after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
  • Men who are sexually active with FOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving atezolizumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 150 days (5 months) after the last dose of investigational product.
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Who cannot join

  • Previous autoimmune complication from PD-1 or PD-L1 inhibitor requiring permanent discontinuation of therapy.
  • Previous permanent discontinuation from PD-1 or PD-L1 inhibitor due to an adverse event (patients who had temporary holds or discontinuation of PD-1 or PD-L1 inhibitor and then re-treated are eligible).
  • Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy.
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  • 5. Has a known additional malignancy that is progressing or required treatment ≤ 48 months of study registration. Exceptions: include malignancies with negligible risk of metastasis or death treated with expected curative outcome or undergoing surveillance per investigator's discretion (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, ductal carcinoma in situ treated surgically with curative intent, or very low risk or low risk prostate cancer per NCCN guidelines).
  • Active central nervous system (CNS) metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression within 28 days prior to the first dose of atezolizumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
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  • Treatment with any investigational drug within 30 days prior to registration.
  • Subjects with an active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids/immunosuppressive medications EXCEPT for syndromes which would not be expected to recur in the absence of an external trigger. (Subjects with vitiligo, autoimmune thyroiditis, or type I diabetes mellitus are permitted to enroll.).
  • As there is potential for hepatic toxicity with atezolizumab, drugs with a predisposition to hepatoxicity should be used with caution in subjects treated with atezolizumab-containing regimen.
  • Subjects should be excluded if they have known history of testing positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. Testing is not required.
  • Subjects should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Testing is not required.
  • History of allergy to atezolizumab or respective chemotherapy regimen (carboplatin + gemcitabine or docetaxel).

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87102

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio, 45267

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Nebraska Methodist Hosptial

    Omaha, Nebraska, 68114

Other trials in United States

About this study

Official title: A Phase II Trial of Atezolizumab Plus Chemotherapy After Progression on PD-1 or PD-L1 Inhibitor in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma: HCRN GU17-295

This is a single arm phase II study assessing the activity of atezolizumab in combination with carboplatin + gemcitabine or docetaxel compared to historical controls of chemotherapy only in metastatic or recurrent urothelial carcinoma subjects. Subjects that received a PD 1 or PD-L1 inhibitor with no prior platinum chemotherapy for metastatic disease will be treated with atezolizumab + carboplatin + gemcitabine on trial. Subjects that received sequential or concurrent PD1/PDL1 inhibitor and carboplatin-based regimen will be treated with atezolizumab + docetaxel on trial.

Medical subject headings
Carcinoma, Transitional Cell

What participants receive

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

  • CarboplatinDrug

    Also called paraplatin

    Carboplatin AUC 4 IV Day 1 of each 21 day cycle

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine 1,000 mg/m2 IV Day 1 and Day 8 of each 21 day cycle

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab 1,200 mg IV Day 1 of each 21 day cycle

  • DocetaxelDrug

    Also called Taxotere

    Docetaxel 75 mg/m2 IV Day 1 of each 21 day Cycle.

Study groups in NCT03737123
Study groupRoleWhat they receive
Chemotherapy and AtezolizumabExperimentalSubjects that received a PD 1 or PD-L1 inhibitor with no prior platinum chemotherapy for metastatic disease will be treated with atezolizumab + carboplatin + gemcitabine on trial. Subjects that received sequential or concurrent PD1/PDL1 inhibitor and carboplatin-based regimen will be treated with atezolizumab + docetaxel on trial.
Receives: Drug: Carboplatin; Drug: Gemcitabine; Drug: Atezolizumab; Drug: Docetaxel

What is being measured

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

  1. Progression Free Survival (PFS)

    Evaluate PFS among patients to be treated with atezolizumab in combination with carboplatin + gemcitabine or docetaxel, who have cisplatin-ineligible metastatic urothelial carcinoma and who have progressed on prior PD-1 or PD-L1 inhibitor. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.

    Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

    Measured: From C1D1 until progression or death or up to a maximum of 26 months

Secondary outcomes (10)

  1. Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Carboplatin + Gemcitabine or Docetaxel

    Assess the safety and tolerability of the combination of atezolizumab plus chemotherapy (carboplatin + gemcitabine or docetaxel) using CTCAE v4.03. Number of subjects who had any adverse events or events greater than grade 3 were reported in this outcome measure.

    Measured: From C1D1 until death or up to a maximum of 8 months

  2. Objective Response Rate (ORR) With RECIST 1.1

    Objective response rate (ORR) using RECIST 1.1 defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

    Measured: From C1D1 until death or up to a maximum of 28 months.

  3. Objective Response Rate (ORR) With irRECIST

    ORR defined as the proportion of all subjects with confirmed PR or CR using immunerelated response criteria (irRECIST), from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).

    Per irRECIST for target lesions Complete Response (irCR), Disappearance of all target lesions; Partial Response (irPR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = irCR + irPR.

    Measured: From C1D1 until death or up to a maximum of 28 months.

  4. Clinical Benefit Rate (CBR) With RECIST 1.1

    Clinical benefit rate (CBR) of treatment (defined by proportion of all subjects with stable disease for at least 3 months, partial response, or complete response) using RECIST 1.1 from the start of treatment until disease/recurrence(taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started; Clinical Benefit Rate (CBR) = CR +PR +SD (for atleast 3 months).

    Measured: From C1D1 until death or up to a maximum of 28 months.

  5. Clinical Benefit Rate (CBR) With irRECIST

    Clinical benefit rate (CBR) of treatment (defined by proportion of all subjects with stable disease for at least 3 months, partial response, or complete response) using irRECIST from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).

    Per irRECIST for target lesions: Complete Response (irCR), Disappearance of all target lesions; Partial Response (irPR), >=30% decrease in the sum of the longest diameter of target lesions, neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for irPD, taking as reference the smallest sum longest diameter since the treatment started; Clinical Benefit Rate (CBR) = irCR +irPR +irSD (for atleast 3 months).

    Measured: From C1D1 until death or up to a maximum of 28 months.

  6. PFS by irRECIST

    PFS defined as duration from date of treatment start until progression according to irRECIST criteria or death from any cause. Per irRECIST criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

    Measured: From C1D1 until progression or death or up to a maximum of 26 months

  7. Overall Survival (OS)

    OS defined by the date of treatment start to date of death from any cause.

    Measured: From C1D1 until death or up to a maximum of 28 months

  8. Progression Free Survival (PFS) Compared to Historical Controls

    To compare Progression Free Survival(PFS) with the historical control, Null hypothesis - Patients receiving atezolizumab plus chemotherapy (carboplatin +gemcitabine or docetaxel) will have a median PFS of 4 months.

    Alternative hypothesis - Patients receiving atezolizumab plus chemotherapy (carboplatin + gemcitabine or docetaxel) will have a median PFS of 7.2 months.

    Progression Free Survival defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

    Measured: From C1D1 until progression or death or up to a maximum of 26 months

  9. Progression Free Survival (PFS) for Atezolizumab + Carboplatin and Gemcitabine

    Evaluate PFS for atezolizumab + carboplatin and gemcitabine. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

    Measured: From C1D1 until death or progression or up to a maximum of 26 months

  10. Progression Free Survival (PFS) for Atezolizumab + Docetaxel

    Evaluate PFS for atezolizumab + docetaxel. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause. Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

    Measured: From C1D1 until progression or death

Timeline

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

  1. First posted9 Nov 2018
  2. Study start19 Dec 2018
  3. Primary completion8 Mar 2022
  4. Study completion18 May 2022

Why it stopped: Lack of accrual

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03737123
Sponsor's protocol ID
GU17-295
Status last verified
Aug 2023
First submitted
8 Nov 2018
Last updated
13 Sep 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Gemcitabine and Atezolizumab in people with Urothelial Carcinoma, run by Nabil Adra at 4 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 28 inclusion and 12 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: stopped early, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 13 Sep 2023). 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?

Progression Free Survival (PFS) (time frame: From C1D1 until progression or death or up to a maximum of 26 months). 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 NCT03737123.

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 13 Sep 2023.

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