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

Duration of Immune Checkpoint Therapy in Locally Advanced or Metastatic Urothelial Carcinoma: A Randomized Phase 3 Non-Inferiority Trial (IMAGINE)

Status
Active, not recruiting
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04637594
Acronym
IMAGINE
Enrollment
3
Registered
2020-11-20
Start date
2022-05-27
Completion date
2030-09-01
Last updated
2026-03-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urethral Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma

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.

Interventions

DRUGPembrolizumab

Given IV

DRUGNivolumab

Given IV

DRUGAtezolizumab

Given IV

DRUGDurvalumab

Given IV

DRUGAvelumab

Given IV

Sponsors

Alliance for Clinical Trials in Oncology
Lead SponsorOTHER
National Cancer Institute (NCI)
CollaboratorNIH

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion 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

Design outcomes

Primary

MeasureTime frameDescription
Overall Survival (OS) Rate at 12 Months12 monthsOS 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.

Secondary

MeasureTime frameDescription
Progression-free Survival (PFS) Rate at 12 Months12 monthsProgression-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.
Immune-related Progression-free Survival (iPFS) Rate at 12 Months12 monthsImmune-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.
Treatment-free Interval (Arm B)From last dose of immune checkpoint inhibitor (ICI) to initiation of a subsequent systemic treatment or death, assessed up to 5 yearsTreatment-free Interval is the length of time patients are off treatment. A Stratified Cox model will be used to evaluate this outcome.
Rate of Response After Immune Checkpoint Inhibitor (ICI) Rechallenge (Arm B)Up to 5 yearsRate 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.
Number of Patients Experiencing Grade 3 or Greater Adverse Events (AEs)2.5 yearsAdverse events (AEs) are ailments occurring during treatment. AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.0.

Countries

United States

Contacts

STUDY_CHAIRXiao X. Wei, MD, MAS

Dana-Farber Cancer Institute

Baseline characteristics

Characteristic
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
1 Participants
Age, Categorical
Between 18 and 65 years
1 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
1 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
1 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
White
1 Participants
Region of Enrollment
United States
3 participants
Sex: Female, Male
Female
0 Participants
Sex: Female, Male
Male
1 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 10 / 2
other
Total, other adverse events
1 / 11 / 2
serious
Total, serious adverse events
0 / 10 / 2

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Mar 21, 2026