NCT04637594|Active Not RecruitingPhase 3ResultsDMCFDA Drug

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

IMAGINE

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

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

Compare

3 other identifiers

A031901NCI-2020-08395U10CA180821

Study Type

interventional

Target

Locations

1 country

Sites

377

Timeline

RegisteredNov 2020

StartedMay 2022

CompletionSep 2030

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_3

Timeline

53mo left

Started May 2022

Longer than P75 for phase_3

Geographic Reach

1 country

377 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8.3 years study duration

Study Progress48%

May 2022Sep 2030

First Submitted

Initial submission to the registry

November 16, 2020

Completed

4 days until next milestone

First Posted

Study publicly available on registry

November 20, 2020

Completed

1.5 years until next milestone

Study Start

First participant enrolled

May 27, 2022

Completed

2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2024

Completed

1.8 years until next milestone

Results Posted

Study results publicly available

March 20, 2026

Completed

4.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2030

Expected

Last Updated

March 20, 2026

Status Verified

March 1, 2026

Enrollment Period

2 years

First QC Date

November 16, 2020

Results QC Date

April 22, 2025

Last Update Submit

March 2, 2026

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

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS) Rate at 12 Months
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.
12 months

Secondary Outcomes (5)

Progression-free Survival (PFS) Rate at 12 Months
12 months
Immune-related Progression-free Survival (iPFS) Rate at 12 Months
12 months
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 years
Rate of Response After Immune Checkpoint Inhibitor (ICI) Rechallenge (Arm B)
Up to 5 years
Number of Patients Experiencing Grade 3 or Greater Adverse Events (AEs)
2.5 years

Study Arms (2)

Arm A (immune checkpoint inhibitor)

ACTIVE COMPARATOR

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.

Drug: PembrolizumabDrug: NivolumabDrug: AtezolizumabDrug: DurvalumabDrug: Avelumab

Arm B (immune checkpoint inhibitor)

EXPERIMENTAL

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.

Drug: PembrolizumabDrug: NivolumabDrug: AtezolizumabDrug: DurvalumabDrug: Avelumab

Interventions

PembrolizumabDRUG

Given IV

Arm A (immune checkpoint inhibitor)Arm B (immune checkpoint inhibitor)

NivolumabDRUG

Given IV

Arm A (immune checkpoint inhibitor)Arm B (immune checkpoint inhibitor)

AtezolizumabDRUG

Given IV

Arm A (immune checkpoint inhibitor)Arm B (immune checkpoint inhibitor)

DurvalumabDRUG

Given IV

Arm A (immune checkpoint inhibitor)Arm B (immune checkpoint inhibitor)

AvelumabDRUG

Given IV

Arm A (immune checkpoint inhibitor)Arm B (immune checkpoint inhibitor)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

* 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator

Study Sites (377)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC