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

NCT02628132 | Completed Phase 1 DMC

• 2 other identifiers: 2151-169ESR-14-10649
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

triple negative; breast cancer; durvalumab; paclitaxel; safety; efficacy; PD-L1; PD-1; Metastatic; AstraZeneca; MEDI4736

Outcome Measures

Primary Outcomes (1)

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

  12 months

Secondary Outcomes (2)

• Objective response rate (ORR)

  24 months

• Progression free survival

  24 months

Study Arms (1)

Durvalumab and Paclitaxel

EXPERIMENTAL

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; Drug: Durvalumab

Interventions

Paclitaxel DRUG

Paclitaxel will be given weekly for 6 cycles

Durvalumab and Paclitaxel

Durvalumab DRUG

Durvalumab will be given q2 wks concurrently with paclitaxel.

Also known as: MEDI4736

Durvalumab and Paclitaxel

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• King Faisal Specialist Hospital & Research Center: lead
• AstraZeneca: collaborator

Study Sites (1)

King Faisal Specialist Hospital and Research Center

Riyadh, 11211, Saudi Arabia

Location

Related Publications (4)

• 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.

  PMID: 16611412 BACKGROUND

• 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.

  PMID: 26245467 BACKGROUND

• 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.

  PMID: 24917416 BACKGROUND

• 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.

  PMID: 34580336 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Paclitaxel; durvalumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2015
• First Posted: December 11, 2015
• Study Start: November 1, 2016
• Primary Completion: December 31, 2019
• Study Completion: March 24, 2020
• Last Updated: July 7, 2020

Record last verified: 2019-10

Locations

SA (1)