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A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer (BEGONIA)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03742102
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : April 24, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:
This study is designed to determine the efficacy and safety of durvalumab in combination with novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel for first-line metastatic triple negative breast cancer

Condition or disease Intervention/treatment Phase
Triple Negative Breast Neoplasms Drug: Durvalumab Drug: Capivasertib Drug: Oleclumab Drug: Paclitaxel Drug: Trastuzumab deruxtecan Drug: Datopotamab deruxtecan Phase 1 Phase 2

Detailed Description:

This is a Phase IB/II, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab in combination with novel oncology therapies (i.e. therapies designed for immune modulation) with or without paclitaxel and durvalumab + paclitaxel as first-line treatment in patients with metastatic triple negative breast cancer (TNBC). The study is designed to concurrently evaluate potential novel treatment combinations with clinical promise using a 2-stage approach. The study will use a Simon 2-Stage design to evaluate which cohorts may proceed to expansion.

Part 1 is a Phase IB study of safety and initial efficacy, and Part 2 may expand patient enrollment if adequate efficacy signal is observed in Part 1. The treatment regimens evaluated in Part 2 will depend on the evaluation of safety and efficacy outcomes in Part 1.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Part 1:

At least 20 patients in the durvalumab-paclitaxel arm and at least 30 patients in each of the other novel treatment combination arms will be enrolled, for a total of approximately 140 patients (durvalumab + paclitaxel arm and 4 novel treatment combination arms). Additional patients may be enrolled in order to have 20 or 30 evaluable (i.e. dosed) patients per durvalumab - paclitaxel arm or novel treatment combination arm, respectively.

Part 2:

Approximately 27 patients will be assigned to each treatment arm, for an anticipated total of 57 response-evaluable patients per arm (ie, 30 patients in Part 1 and 27 patients in Part 2 per treatment arm, with the exception of Arm 1, which will enroll 20 patients in Part 1 and will not be expanded to Part 2). Patient expansion from 30 patients in Part 1 to an additional 27 patients from Part 2 will be determined based on a futility analysis utilizing a Simon 2 Stage design.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IB/II, 2-stage, Open-label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab (MEDI4736) + Paclitaxel and Durvalumab (MEDI4736) in Combination With Novel Oncology Therapies With or Without Paclitaxel for First-line Metastatic Triple Negative Breast Cancer
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : November 14, 2024
Estimated Study Completion Date : November 14, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1
durvalumab + paclitaxel
 Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
Other Name: MEDI4736

Drug: Paclitaxel
Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off
Experimental: Arm 2
durvalumab + paclitaxel + capivasertib
 Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
Other Name: MEDI4736

Drug: Capivasertib
Capivasertib oral bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off
Other Name: AZD5363

Drug: Paclitaxel
Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off
Experimental: Arm 5
durvalumab + paclitaxel + oleclumab
 Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
Other Name: MEDI4736

Drug: Oleclumab
Oleclumab iv Every 2 weeks (q2w) for first 2 cycles (days 1 and 15 in cycles 1 and 2), then every 4 weeks (q4w) starting at cycle 3 day 1
Other Name: MEDI9447

Drug: Paclitaxel
Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off
Experimental: Arm 6
durvalumab + trastuzumab deruxtecan
 Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
Other Name: MEDI4736

Drug: Trastuzumab deruxtecan
Trastuzumab deruxtecan iv 3-week cycles (once weekly) q3w
Other Name: DS-8201a
Experimental: Arm 7
durvalumab + datopotamab deruxtecan
 Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
Other Name: MEDI4736

Drug: Datopotamab deruxtecan
Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w
Other Name: Dato-DXd; DS-1062a
Experimental: Arm 8
durvalumab + datopotomab deruxtecan (patients with PD-L1 positive status)
 Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w) or 3 weeks (q3w) Arm 6, 7 and 8
Other Name: MEDI4736

Drug: Datopotamab deruxtecan
Datopotamab deruxtecan iv 3-week cycles (once weekly) q3w
Other Name: Dato-DXd; DS-1062a


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Part1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. ]

    Part 1: Assessment of safety and tolerability of each treatment arm

    Part 2:

    Endpoints based on Investigator assessment according to RECIST 1.1: ORR (objective response rate): The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR (complete response) or PR (partial response).


  2. Laboratory findings [ Time Frame: Part 1: From informed consent until the safety follow-up visit 3 months after the last dose of study drug. Part 2:From informed consent until the safety follow-up visit 3 months after the last dose of study drug. ]
    Assessment of safety and tolerability of each treatment arm


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Approx. 30 months ]
    Assessment of the efficacy of each treatment arm according to RECIST 1.1. ORR: The percentage of evaluable patients with a confirmed Investigator-assessed response of CR (complete response) or PR (partial response) Applicable for Part 1 and Part 2.

  2. Progression-free survival (PFS). [ Time Frame: On-study tumor assessments occur every 8 weeks (Arms 1-5),every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months ]

    Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of first dose until the date of objective radiological disease progression or death (by any cause in the absence of progression)

    Applicable for Part 1 and Part 2


  3. Duration of response (DoR) [ Time Frame: On-study tumor assessments occur every 8 weeks (Arms 1-5), every 6 weeks (Arms 6-8) until week 48 and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months ]
    Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression Applicable for Part 1 and Part 2

  4. Overall survival (OS) [ Time Frame: Approx. 30 months ]

    OS: Time from date of first dose until the date of death by any cause

    Applicable for Part 1 and Part 2


  5. Serum concentration of durvalumab and serum or plasma concentration of novel oncology therapies [ Time Frame: From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months ]
    Assessment of pharmacokinetics (PK) Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)

  6. Presence of anti-drug antibodies (ADAs) for durvalumab and applicable novel oncology therapies [ Time Frame: From cycle 1 day 1 until cycle 7 day 1 (Arms 1-5), from cycle 1 day 1 until cycle 8 day 1 (Arms 6-8) (each cycle is 28 days) and every 12 weeks thereafter until study completion approx. 30 months ]
    Investigation of the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms Applicable for Part 1 (Arms 1-8) and for Part 2 (Arm 7)

  7. Progression-free survival (PFS 6) [ Time Frame: On-study tumor assessments occur every 8 weeks until week 48 (Arms 1-5), every 6 weeks until week 48 (Arms 6-8) and then every 12 weeks thereafter until radiological progression, death, withdrawal of consent or study completion up to approx. 30 months ]
    PFS at 6 months following date of first dose Applicable for Part 2


Eligibility Criteria
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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 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Female
  2. At least 18 years of age at the time of screening
  3. Patient must have locally confirmed advanced/unresectable or metastatic TNBC.
  4. No prior treatment for metastatic (Stage IV) TNBC
  5. Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured
  6. WHO/ECOG status at 0 or 1 at enrollment

Patients enrolled to Arm 6 (durvalumab and DS-8201a) Must provide documentation of locally determined advanced/unresectable or metastatic TNBC with HER2 low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested)

Patients enrolled in Arm 8 (durvalumab + Dato-DXd) Must have PD-L1 positive tumor as determined by an IHC based assay

Exclusion criteria

  1. History of allogeneic organ transplantation
  2. Active or prior documented autoimmune or inflammatory disorders
  3. Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies)
  4. Untreated CNS metastases
  5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  6. Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment
  7. Female patients who are pregnant, breastfeeding
  8. Cardiac Ejection Fraction less than 50%

Patients enrolled in Arm 2 only:

  1. Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2C9 or CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
  2. Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment.
  3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
  4. Prior treatment with PI3K inhibitors, AKT inhibitors, or mammalian target of rapamycin (mTOR) inhibitors.

Patients enrolled in Arm 5 only: History of venous thromboembolism in the past 3 months

Patients enrolled in Arm 7 and 8 only: Clinically significant corneal disease in the opinion of the Investigator.

Patients enrolled in Arm 6, 7 and 8 only:

  1. History of or active interstitial lung disease/pneumonitis
  2. Use of chloroquine or hydroxychloroquine in <14 days prior to Day 1 of DS-8201a (Arm 6) or Dato-DXd (DS-1062a; Arm 7 and 8) treatment
  3. Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy.
Contacts and Locations
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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): NCT03742102


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AZ Breast Cancer Study Navigators AZ Breast Cancer Study Navigators +1-877-400-4656 AstraZeneca@CareboxHealth.com

Locations
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United States, Arizona
Research Site Recruiting
Goodyear, Arizona, United States, 85395
Research Site Terminated
Tucson, Arizona, United States, 85715
United States, California
Research Site Withdrawn
West Hollywood, California, United States, 90048
United States, Maryland
Research Site Recruiting
Columbia, Maryland, United States, 21044
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02114
Research Site Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site Recruiting
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Research Site Recruiting
Saint Paul, Minnesota, United States, 55102
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, Nevada
Research Site Withdrawn
Las Vegas, Nevada, United States, 89128
United States, Oregon
Research Site Recruiting
Eugene, Oregon, United States, 97401
United States, Pennsylvania
Research Site Withdrawn
Philadelphia, Pennsylvania, United States, 19124
United States, Texas
Research Site Recruiting
Dallas, Texas, United States, 75246
Research Site Recruiting
Flower Mound, Texas, United States, 75028
Research Site Withdrawn
Houston, Texas, United States, 77030
Research Site Recruiting
McAllen, Texas, United States, 78503
Research Site Withdrawn
San Antonio, Texas, United States, 78240
United States, Virginia
Research Site Withdrawn
Fairfax, Virginia, United States, 22031
Research Site Recruiting
Williamsburg, Virginia, United States, 23188
Canada, British Columbia
Research Site Terminated
Kelowna, British Columbia, Canada, V1Y 5L3
Canada, Ontario
Research Site Active, not recruiting
London, Ontario, Canada, N6A 5W9
Research Site Withdrawn
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Research Site Active, not recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Research Site Recruiting
Montreal, Quebec, Canada, H4A 3J1
Korea, Republic of
Research Site Recruiting
Seoul, Korea, Republic of, 03080
Research Site Recruiting
Seoul, Korea, Republic of, 05505
Research Site Recruiting
Seoul, Korea, Republic of, 06351
Poland
Research Site Active, not recruiting
Gdańsk, Poland, 80-214
Research Site Withdrawn
Gliwice, Poland, 44-101
Research Site Active, not recruiting
Kraków, Poland, 31-501
Research Site Active, not recruiting
Lublin, Poland, 20-090
Research Site Active, not recruiting
Opole, Poland, 45-060
Research Site Withdrawn
Poznań, Poland, 61-848
Research Site Active, not recruiting
Rzeszów, Poland, 35-021
Research Site Active, not recruiting
Warszawa, Poland, 02-781
Research Site Completed
Warszawa, Poland, 04-141
Taiwan
Research Site Recruiting
Kaohsiung, Taiwan, 80756
Research Site Recruiting
Taichung, Taiwan, 40447
Research Site Recruiting
Tainan City, Taiwan, 70403
Research Site Recruiting
Taipei, Taiwan, 10002
Research Site Recruiting
Taipei, Taiwan, 112
Research Site Recruiting
Taoyuan, Taiwan, 333
United Kingdom
Research Site Active, not recruiting
Cambridge, United Kingdom, CB2 0QQ
Research Site Active, not recruiting
London, United Kingdom, EC1M 6BQ
Research Site Withdrawn
London, United Kingdom, W1T 7HA
Research Site Active, not recruiting
Manchester, United Kingdom, M20 4BX
Research Site Active, not recruiting
Oxford, United Kingdom, OX3 7LE
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Peter Schmid, MD, PhD Barts Cancer Institute
More Information
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Additional Information:

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03742102    
Other Study ID Numbers: D933LC00001
2018-000764-29 ( EudraCT Number )
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: April 24, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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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:
Breast Cancer
TNBC
Triple Negative
Triple Negative Breast Cancer
Triple-Negative Breast Cancer
 Triple-Negative Breast Neoplasm
ER-Negative PR-Negative HER2-Negative Breast Cancer
ER-Negative PR-Negative HER2-Negative Breast Neoplasms
PD-L1 high TNBC
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Durvalumab
Trastuzumab deruxtecan
 Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs