Trying to Find the Correct Length of Treatment With Immun... | NCT04637594

NCT04637594

ID	Type	Description	Link
NCI-2020-08395	Registry Identifier	NCI Clinical Trial Reporting Program
U10CA180821	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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: Pembrolizumab Drug: Nivolumab Drug: Atezolizumab Drug: Durvalumab Drug: 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: Pembrolizumab Drug: Nivolumab Drug: Atezolizumab Drug: Durvalumab Drug: Avelumab

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Drug	Given IV	Arm A (immune checkpoint inhibitor) Arm B (immune checkpoint inhibitor)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Progression-free Survival (PFS) Rate at 12 Months	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.	12 months

Eligibility Module

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

Name	Affiliation	Role
Xiao X. Wei, MD, MAS	Dana-Farber Cancer Institute	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Anchorage Associates in Radiation Medicine		Anchorage	Alaska	98508	United States
Anchorage Radiation Therapy Center

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 21, 2023

Arm/Group Information

ID	Title	Description
BG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
BG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Number

percentage of participants

12 months

ID	Title	Description
OG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
OG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Units	Counts
Participants	OG0001 OG0012

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Secondary

Progression-free Survival (PFS) Rate at 12 Months

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.

Post baseline assessment was completed for only 1 participant, therefore PFS cannot be calculated

Posted

Number

percentage of participants

12 months

ID	Title	Description
OG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
OG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Secondary

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

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.

Post baseline assessment was completed for only 1 participant, therefore iPFS cannot be calculated

Posted

Number

percentage of participants

12 months

ID	Title	Description
OG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
OG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Secondary

Treatment-free Interval (Arm B)

Treatment-free Interval is the length of time patients are off treatment. A Stratified Cox model will be used to evaluate this outcome.

All patients randomized to arm B withdrew from trial before beginning treatment. No data is available to perform analysis.

Posted

From last dose of immune checkpoint inhibitor (ICI) to initiation of a subsequent systemic treatment or death, assessed up to 5 years

ID	Title	Description
OG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
OG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Secondary

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

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.

All patients randomized to arm B withdrew from trial before beginning treatment. No data is available to perform analysis.

Posted

Up to 5 years

ID	Title	Description
OG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
OG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Secondary

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

Adverse events (AEs) are ailments occurring during treatment. AEs will be assessed using Common Terminology Criteria for Adverse Events version 5.0.

Posted

Count of Participants

Participants

2.5 years

ID	Title	Description
OG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV
OG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV	0	1	0	1	1	1
EG001	Arm B (Immune Checkpoint Inhibitor)	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. Pembrolizumab: Given IV Nivolumab: Given IV Atezolizumab: Given IV Durvalumab: Given IV Avelumab: Given IV	0	2	0	2	1	2

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	CTCAE 5.0	Non-systematic Assessment	EG0002 events1 affected1 at risk EG0010 events0 affected2 at risk
Rotator cuff injury	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Non-systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected2 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE 5.0	Non-systematic Assessment	EG0004 events1 affected1 at risk EG0010 events0 affected2 at risk
Laryngeal inflammation	Respiratory, thoracic and mediastinal disorders	CTCAE 5.0	Non-systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected2 at risk
Papulopustular rash	Infections and infestations	CTCAE 5.0	Non-systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected2 at risk
Hyperkeratosis	Skin and subcutaneous tissue disorders	CTCAE 5.0	Non-systematic Assessment	EG0002 events1 affected1 at risk EG0010 events0 affected2 at risk
Diarrhea	Gastrointestinal disorders	CTCAE 5.0	Non-systematic Assessment	EG0002 events1 affected1 at risk EG0010 events0 affected2 at risk
Fever	General disorders	CTCAE 5.0	Non-systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected2 at risk
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Non-systematic Assessment	EG0002 events1 affected1 at risk EG0010 events0 affected2 at risk
Neoplasms benign, malignant and unspecified - other	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE 5.0	Non-systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected2 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE 5.0	Non-systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected2 at risk
Flu like symptoms	Infections and infestations	CTCAE 5.0	Non-systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected2 at risk
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	CTCAE 5.0	Non-systematic Assessment	EG0001 events1 affected1 at risk EG0010 events0 affected2 at risk
Blurred vision	Eye disorders	CTCAE 5.0	Non-systematic Assessment	EG0000 events0 affected1 at risk EG0011 events1 affected2 at risk

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Term
C582435	pembrolizumab
D000077594	Nivolumab
C000594389	atezolizumab
C000613593	durvalumab
C000609138	avelumab