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Study of Tremelimumab in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02527434
Recruitment Status : Active, not recruiting
First Posted : August 19, 2015
Results First Posted : March 5, 2019
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Urothelial Bladder Cancer Triple-negative Breast Cancer Pancreatic Ductal Adenocarcinoma Biological: Tremelimumab monotherapy Biological: MEDI4736 monotherapy Biological: MEDI4736 + tremelimumab combination therapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Multi-Center, Open-Label Study of Tremelimumab Monotherapy in Patients With Advanced Solid Tumors
Actual Study Start Date : November 2, 2015
Actual Primary Completion Date : February 17, 2018
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: treme mono to be sequenced to MEDI4736 mono or combination
tremelimumab monotherapy, with the option for eligible patients to be sequenced to MEDI4736 monotherapy or MEDI4736 + tremelimumab combination therapy after progressive disease (PD)
Biological: Tremelimumab monotherapy
IV infusion

Biological: MEDI4736 monotherapy
IV infusion

Biological: MEDI4736 + tremelimumab combination therapy
IV infusion




Primary Outcome Measures :
  1. Percentage of Patients With Confirmed Overall Response During Tremelimumab Monotherapy Phase [ Time Frame: From baseline to 12 months in the 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 :
  1. Median Duration of Response (DoR) During Tremelimumab Monotherapy Phase [ Time Frame: From baseline to 12 months in the 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.

  2. Disease Control Rate (DCR) During Tremelimumab Monotherapy Phase [ Time Frame: From baseline to 12 months in the 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.

  3. Median PFS During Tremelimumab Monotherapy Phase [ Time Frame: From baseline to 12 months in the 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.

  4. Best Objective Response (BoR) During Tremelimumab Monotherapy Phase [ Time Frame: From baseline to 12 months in the 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).

  5. Median Overall Survival (OS) During Tremelimumab Monotherapy Phase [ Time Frame: From baseline to final data cut-off date ]

    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.


  6. Percentage of Patients With Confirmed Overall Response During Retreatment Phase [ Time Frame: From baseline to 12 months in 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.

  7. Median DoR During Retreatment Phase [ Time Frame: From baseline to 12 months in 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.

  8. DCR During Retreatment Phase [ Time Frame: From baseline to 4 months in 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.

  9. Median PFS During Retreatment Phase [ Time Frame: From baseline to 12 months in 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.


  10. BoR During Retreatment Phase [ Time Frame: From baseline to 12 months in 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).

  11. Median OS During Retreatment Phase [ Time Frame: From baseline in retreatment phase to final data cut-off date ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 150 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527434


Locations
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United States, California
Research Site
San Francisco, California, United States, 94158
United States, Tennessee
Research Site
Memphis, Tennessee, United States, 38120
United States, Texas
Research Site
Houston, Texas, United States, 77030
Belgium
Research Site
Brussels, Belgium, 1090
Research Site
Charleroi, Belgium, 6000
Research Site
Wilrijk, Belgium, 2610
Korea, Republic of
Research Site
Daejeon, Korea, Republic of, 35015
Research Site
Seoul, Korea, Republic of, 03080
Research Site
Seoul, Korea, Republic of, 03722
Research Site
Seoul, Korea, Republic of, 135-710
Netherlands
Research Site
Groningen, Netherlands, 9713 GZ
Research Site
Utrecht, Netherlands, 3584 CX
Poland
Research Site
Gdańsk, Poland, 80-214
Research Site
Łódź, Poland, 93-513
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Sharma Padmanee, MD, PhD Anderson Cancer Center, the University of Texas
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Statistical Analysis Plan  [PDF] June 22, 2018
Study Protocol  [PDF] September 13, 2018


Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02527434    
Other Study ID Numbers: D4884C00001
2015-002934-32 ( EudraCT Number )
First Posted: August 19, 2015    Key Record Dates
Results First Posted: March 5, 2019
Last Update Posted: February 18, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Urothelial bladder cancer, Triple-negative breast cancer, Pancreatic ductal adenocarcinoma, Advanced Solid Tumors, Tremelimumab, MEDI4736, ORR
Additional relevant MeSH terms:
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Adenocarcinoma
Urinary Bladder Neoplasms
Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs