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NCT04637594 · REGISTRY CONDITION SEARCH

Trying to Find the Correct Length of Treatment With Immune Checkpoint Therapy

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-03-20

This phase III trial compares survival in urothelial cancer patients who stop immune checkpoint inhibitor treatment after being treated for about a year to those patients who continue treatment with immune checkpoint inhibitors. Immunotherapy with monoclonal antibodies, such as avelumab, durvalumab, pembrolizumab, atezolizumab, and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stopping immune checkpoint inhibitors early may still make the tumor shrink and patients may have similar survival rates as the patients who continue treatment. Stopping treatment early may also lead to fewer treatment-related side effects, an improvement in mental health, and a lower cost burden to patients.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS) Rate at 12 Months

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outcome · POSTED

Progression-free Survival (PFS) Rate at 12 Months

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outcome · POSTED

Immune-related Progression-free Survival (iPFS) Rate at 12 Months

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outcome · POSTED

Treatment-free Interval (Arm B)

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outcome · POSTED

Rate of Response After Immune Checkpoint Inhibitor (ICI) Rechallenge (Arm B)

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outcome · POSTED

Number of Patients Experiencing Grade 3 or Greater Adverse Events (AEs)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
* Documentation of disease * Histologic documentation: Histologically or cytologically confirmed urothelial carcinoma (UC) with predominantly transitional-cell features * Stage: Locally advanced or metastatic disease prior to starting immune checkpoint blockade * Tumor Site: Bladder, renal pelvis, ureter, urethra, or prostate * Patients must have received at least one cycle of current active treatment with standard of care (SOC) Food and Drug Administration (FDA) approved PD-1/L1 immune checkpoint inhibitor (ICI)-containing therapy for locally advance or metastatic UC * Patients without progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 guidelines (i.e., with an ongoing \[complete response\] CR, partial response \[PR\], or stable disease \[SD\]) following completion of 12-15 months of ICI treatment * No history of tuberculosis, active hepatitis B (HBV) or hepatitis C (HCV), or uncontrolled human immunodeficiency virus (HIV) * Patients with resolved HBV infection, defined as positive hepatitis B core antibody (anti-Hb) and negative hepatitis B surface antigen (HbsAg), are eligible * Patients with positive HCV antibody are eligible if HCV ribonucleic acid (RNA) polymerase chain reaction (PCR) is negative * Patients with HIV who are compliant with highly active antiretroviral therapy (HAART) and have normal CD4 count and undetectable viral load are eligible * No history of allogeneic organ transplantation * No current immunosuppressive medication exceeding 10 mg/day of prednisone or its equivalent \* Patients with pre-existing or treatment-emergent autoimmune or inflammatory disorders which do not require systemic immunosuppressive treatment exceeding 10 mg/day of prednisone or its equivalent may be included * No history of another primary malignancy except for malignancy treated with curative intent with no known active disease for \>= 2 years, and adequately treated non-melanomatous skin cancer or carcinoma in situ (e.g. cervical carcinoma in situ \[CIS\]) without evidence of disease * No female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control, because this study involves investigational agents whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test pregnancy test done =\< 14 days prior to registration is required REGISTRATION ELIGIBILITY CRITERIA: * Patients without progressive disease per RECIST v 1.1 guidelines (i.e., with an ongoing CR, PR or SD) following completion of 12-15 months of ICI treatment * No toxicity from ICI therapy that makes continuation of treatment clinically unacceptable * Adequate bone marrow and organ functions to continue PD-1/L1 ICI as judged by the treating physician * Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Central nervous system (CNS) metastasis is allowed if radiographically stable, clinically asymptomatic, and prior local therapy (if received) was completed \> 6 months before registration * No history of tuberculosis, active hepatitis B (HBV) or hepatitis C (HCV), or uncontrolled human immunodeficiency virus (HIV) * Patients with resolved HBV infection, defined as positive hepatitis B core antibody (anti-Hb) and negative hepatitis B surface antigen (HbsAg), are eligible * Patients with positive HCV antibody are eligible if HCV RNA PCR is negative * Patients with HIV who are compliant with highly active antiretroviral therapy (HAART) and have normal CD4 count and undetectable viral load are eligible
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    CONTINUATION OF ICI TREATMENT: Patients receive either pembrolizumab intravenously (IV) over 30 minutes on day 1, nivolumab IV over 30 minutes on days 1 and 15, atezolizumab IV over 30-60 minutes on day 1, durvalumab IV over 60 minutes on days 1 and 15, or avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 21 or 42 days for pembrolizumab, every 21 days for atezolizumab, and 28 days for nivolumab, durvalumab, and avelumab in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: Pembrolizumab
    2. Drug: Nivolumab
    3. Drug: Atezolizumab
    4. Drug: Durvalumab
    5. Drug: Avelumab
    label
    Arm A (immune checkpoint inhibitor)
    type
    ACTIVE_COMPARATOR
  2. description
    DISCONTINUATION OF ICI TREATMENT: Patients receiving ICI treatment will discontinue ICI treatment within 1 cycle length after randomization. Cycle length is determined by the ICI regimen the patient is receiving at randomization. At disease progression patients may restart the same ICI treatment they were receiving upon randomization at physician discretion.
    intervention Names
    1. Drug: Pembrolizumab
    2. Drug: Nivolumab
    3. Drug: Atezolizumab
    4. Drug: Durvalumab
    5. Drug: Avelumab
    label
    Arm B (immune checkpoint inhibitor)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A (immune checkpoint inhibitor)
    2. Arm B (immune checkpoint inhibitor)
    description
    Given IV
    name
    Pembrolizumab
    type
    DRUG
  2. arm Group Labels
    1. Arm A (immune checkpoint inhibitor)
    2. Arm B (immune checkpoint inhibitor)
    description
    Given IV
    name
    Nivolumab
    type
    DRUG
  3. arm Group Labels
    1. Arm A (immune checkpoint inhibitor)
    2. Arm B (immune checkpoint inhibitor)
    description
    Given IV
    name
    Atezolizumab
    type
    DRUG
  4. arm Group Labels
    1. Arm A (immune checkpoint inhibitor)
    2. Arm B (immune checkpoint inhibitor)
    description
    Given IV
    name
    Durvalumab
    type
    DRUG
  5. arm Group Labels
    1. Arm A (immune checkpoint inhibitor)
    2. Arm B (immune checkpoint inhibitor)
    description
    Given IV
    name
    Avelumab
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
3
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    OS is the length of time patients are alive after registering to receive protocol treatment. Patients who are lost to follow-up or are not known to be deceased at the time of study analysis will be censored at the time of last patient contact. Cox models will be used to compare the outcome between the two treatment groups.
    measure
    Overall Survival (OS) Rate at 12 Months
    time Frame
    12 months
secondary Outcomes
  1. description
    Progression-free survival (PFS) is the length of time patients are alive without disease progression. Progression will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Stratified Cox models will be used to compare the outcomes between the two treatment groups.
    measure
    Progression-free Survival (PFS) Rate at 12 Months
    time Frame
    12 months
  2. description
    Immune-related progression-free survival (iPFS) is the length of time patients are alive without immune-related progression. Progression will be assessed using immune related (ir)RECIST criteria. Stratified Cox models will be used to compare the outcomes between the two treatment groups.
    measure
    Immune-related Progression-free Survival (iPFS) Rate at 12 Months
    time Frame
    12 months
  3. description
    Treatment-free Interval is the length of time patients are off treatment. A Stratified Cox model will be used to evaluate this outcome.
    measure
    Treatment-free Interval (Arm B)
    time Frame
    From last dose of immune checkpoint inhibitor (ICI) to initiation of a subsequent systemic treatment or death, assessed up to 5 years
  4. description
    Rate of response is the percentage of patients with response after re-initiation of immune checkpoint inhibitor (ICI) therapy after progression post-registration. Rate of response will be assessed using RECIST 1.1. A chi-square test (or Fisher's exact test) will be used to determine whether there is an association between the best tumor response prior to trial enrollment and that achieved upon ICI re-challenge.
    measure
    Rate of Response After Immune Checkpoint Inhibitor (ICI) Rechallenge (Arm B)
    time Frame
    Up to 5 years
  5. description
    Adverse events (AEs) are ailments occurring during treatment. AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
    measure
    Number of Patients Experiencing Grade 3 or Greater Adverse Events (AEs)
    time Frame
    2.5 years
Full study description
brief Summary
This phase III trial compares survival in urothelial cancer patients who stop immune checkpoint inhibitor treatment after being treated for about a year to those patients who continue treatment with immune checkpoint inhibitors. Immunotherapy with monoclonal antibodies, such as avelumab, durvalumab, pembrolizumab, atezolizumab, and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stopping immune checkpoint inhibitors early may still make the tumor shrink and patients may have similar survival rates as the patients who continue treatment. Stopping treatment early may also lead to fewer treatment-related side effects, an improvement in mental health, and a lower cost burden to patients.
detailed Description
PRIMARY OBJECTIVE: I. To compare overall survival (OS). SECONDARY OBJECTIVES: I. To compare progression free survival (PFS) by (Response Evaluation Criteria in Solid Tumors) RECIST 1.1 criteria. II. To compare PFS by immune-related (ir)RECIST criteria. III. To determine treatment-free interval (TFI) after immune checkpoint inhibitor (ICI) discontinuation. (Arm B) IV. To determine the rate of response by RECIST 1.1 criteria after ICI rechallenge. (Arm B) V. To assess adverse events in each study arm by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. OUTLINE: Patient are randomized to 1 of 2 arms. ARM A (CONTINUATION OF ICI TREATMENT): Patients receive either pembrolizumab intravenously (IV) over 30 minutes on day 1, nivolumab IV over 30 minutes on days 1 and 15, atezolizumab IV over 30-60 minutes on day 1, durvalumab IV over 60 minutes on days 1 and 15, or avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 21 or 42 days for pembrolizumab, every 21 days for atezolizumab, and 28 days for nivolumab, durvalumab, and avelumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, starting new treatment or withdrawn consent, patients are followed up at 4 weeks, and then every 6 months for 5 years following registration. ARM B (DISCONTINUATION OF ICI TREATMENT): Patients receiving ICI treatment will discontinue ICI treatment within 1 cycle length after randomization. Cycle length is determined by the ICI regimen the patient is receiving at randomization. At disease progression patients may restart the same ICI treatment they were receiving upon randomization at physician discretion. After completion of study treatment, patients are followed up at 4 weeks, and then every 6 months for 5 years following registration.
Source references
Source notices and limitations
    Discovery and provenance
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        exact text
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      offset unit
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      query cond
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      query disease state id
      ds-urethral-cancer
      source file
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      source file sha256
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    Preserved source evidence · Not medical advice