- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02628132
Study of Safety and Efficacy of Durvalumab in Combination With Paclitaxel in Metastatic Triple Negative Breast Cancer Patients
Study of the Safety, Tolerability and Efficacy of the Investigational Anti PD-L1 Monoclonal Antibody Durvalumab in Combination With Paclitaxel in Patients With Metastatic Triple Negative PD-L1 Positive Breast Cancer
The expression of PD-L1 in breast cancer has been previously demonstrated (Ghebeh et al 2006). In addition, PD-L1 has been shown to work as a "molecular shield", by protecting cancer cells from cytotoxic T-cells and chemotherapy induced apoptosis (Ghebeh et al 2008) suggesting to combine PD-L1 blockade with chemotherapy.
This trial will test Durvalumab in combination with Paclitaxel on metastatic triple-negative breast cancer patients. The safety profile of Durvalumab as a monotherapy has been previously established (lu et al 2015). In this trial the safety profile and tolerability of Durvalumab given in combination of Paclitaxel will be tested. In addition, the efficacy of this combination on metastatic breast cancer will be monitored.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Riyadh, Saudi Arabia, 11211
- King Faisal Specialist Hospital and Research Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed metastatic breast cancer
- Triple negative breast cancer (estrogen receptor (ER) negative, progesterone receptor (PR) negative and Her2/neu negative).
- Patients had received at least 1 line of chemotherapy in metastatic setting before being enrolled in this trial.
- Written informed consent and any locally-required authorization
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Life expectancy of >12 weeks
- Adequate normal organ and marrow functions.
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study or previous enrolment in the present study
- Participation in another clinical study with an investigational product during the last 4 months
- Any previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736 or with a CTLA 4 inhibitor
- Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
- Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of 10 mg dexamethasone prior to paclitaxel infusion and intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Active or prior documented autoimmune disease within the past 2 years
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- History of primary immunodeficiency
- History of allogeneic organ transplant
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, interstitial lung disease (ILD), cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- History of leptomeningeal carcinomatosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736
- Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
- Subjects with uncontrolled seizures.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Durvalumab and Paclitaxel
After one cycle of paclitaxel, durvalumab will be given concurrently with paclitaxel.
Once paclitaxel cycles are completed, durvalumab will be continued alone until disease progression or unacceptable toxicity.
|
Paclitaxel will be given weekly for 6 cycles
Durvalumab will be given q2 wks concurrently with paclitaxel.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of patients with adverse events (severe and non-severe)
Time Frame: 12 months
|
12 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective response rate (ORR)
Time Frame: 24 months
|
24 months
|
Progression free survival
Time Frame: 24 months
|
24 months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Hazem Ghebeh, B.Pharm, Ph.D., Research Center, King Faisal Specialist Hospital & Research Center
- Principal Investigator: Taher Al-Tweigeri, M.D., Oncology Center, King Faisal Specialist Hospital & Research Center
Publications and helpful links
General Publications
- Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G, Elkum N, Alshabanah M, Bin Amer S, Tulbah A, Ajarim D, Al-Tweigeri T, Dermime S. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia. 2006 Mar;8(3):190-8. doi: 10.1593/neo.05733.
- Alsuliman A, Colak D, Al-Harazi O, Fitwi H, Tulbah A, Al-Tweigeri T, Al-Alwan M, Ghebeh H. Bidirectional crosstalk between PD-L1 expression and epithelial to mesenchymal transition: significance in claudin-low breast cancer cells. Mol Cancer. 2015 Aug 7;14:149. doi: 10.1186/s12943-015-0421-2.
- Lu J, Lee-Gabel L, Nadeau MC, Ferencz TM, Soefje SA. Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy. J Oncol Pharm Pract. 2015 Dec;21(6):451-67. doi: 10.1177/1078155214538087. Epub 2014 Jun 9.
- Ghebeh H, Al-Sayed A, Eiada R, Cabangon L, Ajarim D, Suleman K, Tulbah A, Al-Tweigeri T. Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer. Sci Rep. 2021 Sep 27;11(1):19154. doi: 10.1038/s41598-021-98113-6.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2151-169
- ESR-14-10649 (Other Grant/Funding Number: AstraZeneca)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Baylor Breast Care CenterRecruitingBreast Cancer | Breast Neoplasm | Triple Negative Breast Cancer | Triple Negative Breast Neoplasms | HER2-positive Breast Cancer | Breast Cancer Stage II | Breast Cancer Female | Breast Cancer Stage III | Estrogen Receptor-positive Breast Cancer | Hormone Receptor-positive Breast Cancer | Breast Cancer InvasiveUnited States
-
Innocrin PharmaceuticalCompletedBreast Cancer | Advanced Breast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | Male Breast Cancer | ER+ Breast Cancer | Cancer of the BreastUnited States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)WithdrawnStage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast Cancer
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
Clinical Trials on Paclitaxel
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Breast Carcinoma | Stage IV Breast Cancer AJCC v6 and v7 | Stage III Breast Cancer AJCC v7 | Stage IIIA Breast Cancer AJCC v7 | Stage IIIB Breast Cancer AJCC v7 | Stage IIIC Breast Cancer AJCC v7 | Metastatic Breast Carcinoma | Locally Advanced Breast CarcinomaUnited States
-
Anne NoonanNational Cancer Institute (NCI)RecruitingStage IV Pancreatic Cancer AJCC v8 | Metastatic Pancreatic AdenocarcinomaUnited States
-
Hutchison Medipharma LimitedSun Yat-sen UniversityActive, not recruitingAdvanced Gastric CancerChina
-
University of WashingtonNational Cancer Institute (NCI); Celgene CorporationCompletedRecurrent Non-Small Cell Lung Carcinoma | Stage IV Non-Small Cell Lung CancerUnited States
-
Shengjing HospitalRecruiting
-
CTI BioPharmaTerminatedNSCLCUnited States, Canada, Bulgaria, Romania, Russian Federation, Ukraine, Mexico, Argentina, Hungary, Poland, United Kingdom
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnRecurrent Bladder Urothelial Carcinoma | Stage IV Bladder Urothelial CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAnatomic Stage I Breast Cancer AJCC v8 | Anatomic Stage IA Breast Cancer AJCC v8 | Anatomic Stage IB Breast Cancer AJCC v8 | Anatomic Stage II Breast Cancer AJCC v8 | Anatomic Stage IIA Breast Cancer AJCC v8 | Anatomic Stage IIB Breast Cancer AJCC v8 | Anatomic Stage III Breast Cancer AJCC v8 | Anatomic... and other conditionsUnited States
-
CTI BioPharmaTerminated
-
Novartis PharmaceuticalsCompletedMetastatic or Locally Advanced Solid TumorsNetherlands, Spain, Germany, Switzerland, Belgium