Study of Tremelimumab in Patients With Advanced Solid Tumors

Pancreatic Ductal Adenocarcinoma Clinical Trial

Official title:

A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527434
• Other study ID #: D4884C00001
• Secondary ID: 2015-002934-32
• Status: Completed
• Phase: Phase 2
• Start date: November 2, 2015
• Est. completion date: March 28, 2023

Study information

• Verified date: October 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients with Advanced Solid Tumors

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 28, 2023
• Est. primary completion date: February 17, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 150 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma
• Triple Negative Breast Neoplasms
• Triple-negative Breast Cancer
• Urinary Bladder Neoplasms
• Urothelial Bladder Cancer

Intervention

Biological:
• Tremelimumab monotherapy
IV infusion
• MEDI4736 monotherapy
IV infusion
• MEDI4736 + tremelimumab combination therapy
IV infusion

Locations

Country	Name	City	State
Belgium	Research Site	Brussels
Belgium	Research Site	Charleroi
Belgium	Research Site	Wilrijk
Korea, Republic of	Research Site	Daejeon
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Groningen
Netherlands	Research Site	Utrecht
Poland	Research Site	Gdansk
Poland	Research Site	Lódz
United States	Research Site	Houston	Texas
United States	Research Site	Memphis	Tennessee
United States	Research Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Korea, Republic of,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From baseline to 12 months in the tremelimumab monotherapy phase
Secondary	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.	From baseline to 12 months in the tremelimumab monotherapy phase
Secondary	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.	From baseline to 12 months in the tremelimumab monotherapy phase
Secondary	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.	From baseline to 12 months in the tremelimumab monotherapy phase
Secondary	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).	From baseline to 12 months in the tremelimumab monotherapy phase
Secondary	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.	From baseline to final data cut-off date
Secondary	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.	From baseline to 12 months in retreatment phase
Secondary	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.	From baseline to 12 months in retreatment phase
Secondary	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.	From baseline to 4 months in retreatment phase
Secondary	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.	From baseline to 12 months in retreatment phase
Secondary	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).	From baseline to 12 months in retreatment phase
Secondary	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.	From baseline in retreatment phase to final data cut-off date

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