Back to resultsStudy of Tremelimumab in Patients With Advanced Solid Tumors
Primary Purpose
Urothelial Bladder Cancer, Triple-negative Breast Cancer, Pancreatic Ductal Adenocarcinoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tremelimumab monotherapy
MEDI4736 monotherapy
MEDI4736 + tremelimumab combination therapy
Sponsored by
About this trial
This is an interventional treatment trial for Urothelial Bladder Cancer focused on measuring Urothelial bladder cancer, Triple-negative breast cancer, Pancreatic ductal adenocarcinoma, Advanced Solid Tumors, Tremelimumab, MEDI4736, ORR
Eligibility Criteria
Inclusion Criteria:
1. histologically or cytologically documented solid tumor malignancies, including but not limited to 1 of the following: UBC, Metastatic PDAC, TNBC; Are intolerant, are ineligible for, or have refused treatment with standard first-line therapy; 2. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scans and that is suitable for accurate repeated measurements.
Exclusion criteria:
1. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer Treatment; 2. History of leptomeningeal carcinomatosis; 3. Active or prior documented autoimmune or inflammatory disorders; 4. Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 14 days prior to study treatment start; 5. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms; 6. Known allergy or hypersensitivity to IP or any IP excipient
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
treme mono to be sequenced to MEDI4736 mono or combination
Arm Description
tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)
Outcomes
Primary Outcome Measures
Percentage of Patients With Confirmed Overall Response During Tremelimumab Monotherapy Phase
Objective response rate (ORR) during the initial tremelimumab monotherapy phase was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.
Secondary Outcome Measures
Median Duration of Response (DoR) During Tremelimumab Monotherapy Phase
DoR during the initial tremelimumab monotherapy phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The time of the initial response was defined as the latest of the dates contributing toward the first visit response of CR or PR. If a patient did not progress following a response, then their DoR was censored at the progression-free survival (PFS) censoring time. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.
Disease Control Rate (DCR) During Tremelimumab Monotherapy Phase
DCR during the initial tremelimumab monotherapy phase was defined as the percentage of patients who had a best objective response (BoR) of CR or PR in the first 3 months (PDAC patients) or 4 months (UBC and TNBC patients) and 12 months (all patients), or who had demonstrated stable disease (SD) for a minimum interval of 3, 4 or 12 months following the start of study treatment. DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. 95% CIs were calculated using the Clopper Pearson method.
Median PFS During Tremelimumab Monotherapy Phase
PFS during the initial tremelimumab monotherapy phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of enrollment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression. Progression events that did not occur within 3 months (PDAC patients) or 4 months (UBC/TNBC patients) of the last evaluable assessment (or first dose) were censored. Median PFS was calculated using the Kaplan-Meier technique.
Best Objective Response (BoR) During Tremelimumab Monotherapy Phase
BoR during the initial tremelimumab monotherapy phase was calculated based on the overall visit responses from each RECIST 1.1 assessment and was defined as the best response a patient had during their time in the study (from CR, PR, SD, PD or not evaluable [NE]) obtained among all tumor assessment visits from baseline until end of treatment or determination of PD. The BoR was summarized by percentage of patients for each category (CR, PR, SD, PD, and NE).
Median Overall Survival (OS) During Tremelimumab Monotherapy Phase
OS was defined as the time from the date of first dose until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. OS is presented from start of tremelimumab monotherapy phase and includes the retreatment phase if the patient entered the corresponding treatment phase.
Median OS was calculated using the Kaplan-Meier technique.
Percentage of Patients With Confirmed Overall Response During Retreatment Phase
ORR was assessed by the site Investigator using RECIST 1.1 and was defined as the percentage of patients with a confirmed overall response of CR or PR and was based on all treated patients who had measurable disease at baseline (Day 1) and who sequenced to durvalumab monotherapy (MEDI treatment phase) or durvalumab + tremelimumab combination therapy (COMBO treatment phase). 95% CIs were calculated using the Clopper Pearson method.
Median DoR During Retreatment Phase
DoR during the retreatment phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The time of the initial response was defined as the latest of the dates contributing toward the first visit response of CR or PR. If a patient did not progress following a response, then their DoR was censored at the PFS censoring time. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.
DCR During Retreatment Phase
DCR during the retreatment phase was defined as the percentage of patients who had a BoR of CR or PR in the first 3 months (PDAC patients) or 4 months (UBC and TNBC patients) or who had demonstrated SD for a minimum interval of 3 or 4 months following the start of study treatment. DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. 95% CIs were calculated using the Clopper Pearson method.
Median PFS During Retreatment Phase
PFS during the retreatment phase was assessed by the site Investigator using RECIST 1.1 and defined as the time from the date of enrollment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression.
Progression events that did not occur within 3 months (PDAC patients) or 4 months (UBC/TNBC patients) of the last evaluable assessment (or first dose) were censored. Median PFS was calculated using the Kaplan-Meier technique.
BoR During Retreatment Phase
BoR during the retreatment phase was calculated based on the overall visit responses from each RECIST 1.1 assessment and was defined as the best response a patient had during their time in the study (from CR, PR, SD, PD or NE) obtained among all tumor assessment visits from baseline until end of treatment or determination of PD. The BoR was summarized by percentage of patients for each category (CR, PR, SD, PD, and NE).
Median OS During Retreatment Phase
OS during the retreatment phase was defined as the time from the date of first dose until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02527434
Brief Title
Study of Tremelimumab in Patients With Advanced Solid Tumors
Official Title
A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients With Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
November 2, 2015 (Actual)
Primary Completion Date
February 17, 2018 (Actual)
Study Completion Date
March 28, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients with Advanced Solid Tumors
Detailed Description
This is an open-label, multi-center study to determine the efficacy and safety of tremelimumab in the treatment of different cohorts of patients with selected advanced solid tumors. If eligible and at the discretion of the Investigator, after confirmed disease progression on tremelimumab monotherapy or during follow-up, patients will have the option of being sequenced to MEDI4736 (MedImmune 4736) monotherapy or MEDI4736 + tremelimumab combination therapy, for up to 12 months or until disease progression, whichever comes sooner.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Bladder Cancer, Triple-negative Breast Cancer, Pancreatic Ductal Adenocarcinoma
Keywords
Urothelial bladder cancer, Triple-negative breast cancer, Pancreatic ductal adenocarcinoma, Advanced Solid Tumors, Tremelimumab, MEDI4736, ORR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
treme mono to be sequenced to MEDI4736 mono or combination
Arm Type
Experimental
Arm Description
tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)
Intervention Type
Biological
Intervention Name(s)
Tremelimumab monotherapy
Intervention Description
IV infusion
Intervention Type
Biological
Intervention Name(s)
MEDI4736 monotherapy
Intervention Description
IV infusion
Intervention Type
Biological
Intervention Name(s)
MEDI4736 + tremelimumab combination therapy
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Percentage of Patients With Confirmed Overall Response During Tremelimumab Monotherapy Phase
Description
Objective response rate (ORR) during the initial tremelimumab monotherapy phase was assessed by the site Investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) and was defined as the percentage of patients with a confirmed overall response of complete response (CR) or partial response (PR) and was based on all treated patients who had measurable disease at baseline (Day 1). 95% confidence intervals (CIs) were calculated using the Clopper Pearson method.
Time Frame
From baseline to 12 months in the tremelimumab monotherapy phase
Secondary Outcome Measure Information:
Title
Median Duration of Response (DoR) During Tremelimumab Monotherapy Phase
Description
DoR during the initial tremelimumab monotherapy phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The time of the initial response was defined as the latest of the dates contributing toward the first visit response of CR or PR. If a patient did not progress following a response, then their DoR was censored at the progression-free survival (PFS) censoring time. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.
Time Frame
From baseline to 12 months in the tremelimumab monotherapy phase
Title
Disease Control Rate (DCR) During Tremelimumab Monotherapy Phase
Description
DCR during the initial tremelimumab monotherapy phase was defined as the percentage of patients who had a best objective response (BoR) of CR or PR in the first 3 months (PDAC patients) or 4 months (UBC and TNBC patients) and 12 months (all patients), or who had demonstrated stable disease (SD) for a minimum interval of 3, 4 or 12 months following the start of study treatment. DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. 95% CIs were calculated using the Clopper Pearson method.
Time Frame
From baseline to 12 months in the tremelimumab monotherapy phase
Title
Median PFS During Tremelimumab Monotherapy Phase
Description
PFS during the initial tremelimumab monotherapy phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of enrollment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression. Progression events that did not occur within 3 months (PDAC patients) or 4 months (UBC/TNBC patients) of the last evaluable assessment (or first dose) were censored. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame
From baseline to 12 months in the tremelimumab monotherapy phase
Title
Best Objective Response (BoR) During Tremelimumab Monotherapy Phase
Description
BoR during the initial tremelimumab monotherapy phase was calculated based on the overall visit responses from each RECIST 1.1 assessment and was defined as the best response a patient had during their time in the study (from CR, PR, SD, PD or not evaluable [NE]) obtained among all tumor assessment visits from baseline until end of treatment or determination of PD. The BoR was summarized by percentage of patients for each category (CR, PR, SD, PD, and NE).
Time Frame
From baseline to 12 months in the tremelimumab monotherapy phase
Title
Median Overall Survival (OS) During Tremelimumab Monotherapy Phase
Description
OS was defined as the time from the date of first dose until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. OS is presented from start of tremelimumab monotherapy phase and includes the retreatment phase if the patient entered the corresponding treatment phase.
Median OS was calculated using the Kaplan-Meier technique.
Time Frame
From baseline to final data cut-off date
Title
Percentage of Patients With Confirmed Overall Response During Retreatment Phase
Description
ORR was assessed by the site Investigator using RECIST 1.1 and was defined as the percentage of patients with a confirmed overall response of CR or PR and was based on all treated patients who had measurable disease at baseline (Day 1) and who sequenced to durvalumab monotherapy (MEDI treatment phase) or durvalumab + tremelimumab combination therapy (COMBO treatment phase). 95% CIs were calculated using the Clopper Pearson method.
Time Frame
From baseline to 12 months in retreatment phase
Title
Median DoR During Retreatment Phase
Description
DoR during the retreatment phase was assessed by the site Investigator using RECIST 1.1 and was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The time of the initial response was defined as the latest of the dates contributing toward the first visit response of CR or PR. If a patient did not progress following a response, then their DoR was censored at the PFS censoring time. DoR was not defined for those patients who did not have documented response. Median DoR was calculated using the Kaplan-Meier technique.
Time Frame
From baseline to 12 months in retreatment phase
Title
DCR During Retreatment Phase
Description
DCR during the retreatment phase was defined as the percentage of patients who had a BoR of CR or PR in the first 3 months (PDAC patients) or 4 months (UBC and TNBC patients) or who had demonstrated SD for a minimum interval of 3 or 4 months following the start of study treatment. DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. 95% CIs were calculated using the Clopper Pearson method.
Time Frame
From baseline to 4 months in retreatment phase
Title
Median PFS During Retreatment Phase
Description
PFS during the retreatment phase was assessed by the site Investigator using RECIST 1.1 and defined as the time from the date of enrollment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from therapy or received another anticancer therapy prior to progression.
Progression events that did not occur within 3 months (PDAC patients) or 4 months (UBC/TNBC patients) of the last evaluable assessment (or first dose) were censored. Median PFS was calculated using the Kaplan-Meier technique.
Time Frame
From baseline to 12 months in retreatment phase
Title
BoR During Retreatment Phase
Description
BoR during the retreatment phase was calculated based on the overall visit responses from each RECIST 1.1 assessment and was defined as the best response a patient had during their time in the study (from CR, PR, SD, PD or NE) obtained among all tumor assessment visits from baseline until end of treatment or determination of PD. The BoR was summarized by percentage of patients for each category (CR, PR, SD, PD, and NE).
Time Frame
From baseline to 12 months in retreatment phase
Title
Median OS During Retreatment Phase
Description
OS during the retreatment phase was defined as the time from the date of first dose until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
Time Frame
From baseline in retreatment phase to final data cut-off date
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
150 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. histologically or cytologically documented solid tumor malignancies, including but not limited to 1 of the following: UBC, Metastatic PDAC, TNBC; Are intolerant, are ineligible for, or have refused treatment with standard first-line therapy; 2. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scans and that is suitable for accurate repeated measurements.
Exclusion criteria:
1. Any concurrent chemotherapy, biologic, or hormonal therapy for cancer Treatment; 2. History of leptomeningeal carcinomatosis; 3. Active or prior documented autoimmune or inflammatory disorders; 4. Brain metastases or spinal cord compression unless asymptomatic or treated and stable off steroids and anti-convulsants for at least 14 days prior to study treatment start; 5. QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms; 6. Known allergy or hypersensitivity to IP or any IP excipient
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharma Padmanee, MD, PhD
Organizational Affiliation
Anderson Cancer Center, the University of Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Research Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Research Site
City
Charleroi
ZIP/Postal Code
6000
Country
Belgium
Facility Name
Research Site
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Research Site
City
Daejeon
ZIP/Postal Code
35015
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Facility Name
Research Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Research Site
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Research Site
City
Gdańsk
ZIP/Postal Code
80-214
Country
Poland
Facility Name
Research Site
City
Łódź
ZIP/Postal Code
93-513
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3801&filename=D4884C00001-statistical-analysis-plan-edition-2_%2022Jun2018_Published%20on%20CARA-redact.pdf
Description
Related Info
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3801&filename=D4884C00001-csp-v4_final_clean_13Sep2018-redact.pdf
Description
Related Info
Learn more about this trial
Study of Tremelimumab in Patients With Advanced Solid Tumors
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