AzTrials
AzTrials

Breast CancerPhase 1/2NCT02628132

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

A Phase 1/2 study testing Paclitaxel and Durvalumab in people with Breast Cancer, run by King Faisal Specialist Hospital & Research Center at 1 site in Saudi Arabia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Paclitaxel and Durvalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteSaudi Arabia
Study dates
Nov 2016to 24 Mar 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 17Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Saudi Arabia1 site

  • King Faisal Specialist Hospital and Research Center

    Riyadh, 11211

Other trials in Saudi Arabia

About this study

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

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.

Read the 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.

Conditions
Breast Cancer
Being tested
Paclitaxel, Durvalumab
Keywords
triple negative, breast cancer, durvalumab, paclitaxel, safety, efficacy, PD-L1, PD-1, Metastatic, AstraZeneca, MEDI4736
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PaclitaxelDrug

    Paclitaxel will be given weekly for 6 cycles

  • DurvalumabDrug

    Also called MEDI4736

    Durvalumab will be given q2 wks concurrently with paclitaxel.

Study groups in NCT02628132
Study groupRoleWhat they receive
Durvalumab and PaclitaxelExperimentalAfter 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.
Receives: Drug: Paclitaxel; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with adverse events (severe and non-severe)

    Measured: 12 months

Secondary outcomes (2)

  1. Objective response rate (ORR)

    Measured: 24 months

  2. Progression free survival

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2015 (estimated)
  2. Study startNov 2016
  3. Primary completion31 Dec 2019
  4. Study completion24 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02628132
Sponsor's protocol ID
2151-169
Other IDs
ESR-14-10649
Status last verified
Oct 2019
First submitted
29 Nov 2015
Last updated
7 Jul 2020
Results posted
No
Data monitoring committee
Yes

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.

    PubMed 16611412

  • 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.

    PubMed 26245467

  • 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.

    PubMed 24917416

  • 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.

    PubMed 34580336

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Paclitaxel and Durvalumab in people with Breast Cancer, run by King Faisal Specialist Hospital & Research Center at 1 site in Saudi Arabia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Saudi Arabia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of patients with adverse events (severe and non-severe) (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02628132, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in