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Study of Safety and Efficacy of Durvalumab in Combination With Paclitaxel in Metastatic Triple Negative Breast Cancer Patients

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ClinicalTrials.gov Identifier: NCT02628132
Recruitment Status : Active, not recruiting
First Posted : December 11, 2015
Last Update Posted : October 23, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
King Faisal Specialist Hospital & Research Center

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Paclitaxel Drug: Durvalumab Phase 1 Phase 2

Detailed Description:
This open label single arm trial will involve metastatic triple negative PD-L1 positive breast cancer patients. The trial will include a dose deescalation phase where three doses of paclitaxel will be tried on 3 patients each followed by a dose expansion phase on 25 patients. Paclitaxel will be given weekly for 1 cycle followed by combination of Paclitaxel and Durvalumab. Once 6 cycles of Paclitaxel are completed, Durvalumab will be given alone until disease progression or unacceptable toxicity. The toxicity and tolerability of the combination will be the main end point while the efficacy will be a secondary end point.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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.
Drug: Paclitaxel
Paclitaxel will be given weekly for 6 cycles

Drug: Durvalumab
Durvalumab will be given q2 wks concurrently with paclitaxel.
Other Name: MEDI4736




Primary Outcome Measures :
  1. Number of patients with adverse events (severe and non-severe) [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 24 months ]
  2. Progression free survival [ Time Frame: 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed metastatic breast cancer
  2. Triple negative breast cancer (estrogen receptor (ER) negative, progesterone receptor (PR) negative and Her2/neu negative).
  3. Patients had received at least 1 line of chemotherapy in metastatic setting before being enrolled in this trial.
  4. Written informed consent and any locally-required authorization
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  6. Life expectancy of >12 weeks
  7. Adequate normal organ and marrow functions.

Exclusion Criteria:

  1. Involvement in the planning and/or conduct of the study or previous enrolment in the present study
  2. Participation in another clinical study with an investigational product during the last 4 months
  3. Any previous treatment with a PD-1 or PD-L1 inhibitor, including MEDI4736 or with a CTLA 4 inhibitor
  4. Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
  5. 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
  6. Active or prior documented autoimmune disease within the past 2 years
  7. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
  8. History of primary immunodeficiency
  9. History of allogeneic organ transplant
  10. 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
  11. Known history of previous clinical diagnosis of tuberculosis
  12. History of leptomeningeal carcinomatosis
  13. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736
  14. 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
  15. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  16. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
  17. Subjects with uncontrolled seizures.

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): NCT02628132


Locations
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Saudi Arabia
King Faisal Specialist Hospital and Research Center
Riyadh, Saudi Arabia, 11211
Sponsors and Collaborators
King Faisal Specialist Hospital & Research Center
AstraZeneca
Investigators
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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:
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Responsible Party: King Faisal Specialist Hospital & Research Center
ClinicalTrials.gov Identifier: NCT02628132     History of Changes
Other Study ID Numbers: 2151-169
ESR-14-10649 ( Other Grant/Funding Number: AstraZeneca )
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: October 23, 2019
Last Verified: October 2019
Keywords provided by King Faisal Specialist Hospital & Research Center:
triple negative
breast cancer
durvalumab
paclitaxel
safety
efficacy
PD-L1
PD-1
Metastatic
AstraZeneca
MEDI4736
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunologic Factors
Physiological Effects of Drugs