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

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ClinicalTrials.gov Identifier: NCT03742102
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : October 2, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE October 25, 2018
First Posted Date  ICMJE November 15, 2018
Last Update Posted Date October 2, 2019
Actual Study Start Date  ICMJE December 21, 2018
Estimated Primary Completion Date November 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • Incidence of adverse events [ Time Frame: 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
  • Laboratory findings [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03742102 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • Objective response rate (ORR) [ Time Frame: Approximately 24 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 or PR
  • Progression-free survival (PFS). [ Time Frame: On-study tumor assessments occur every 8 weeks until week 48 and then every 12 weeks thereafter until confirmed radiological progression, death, withdrawal of consent or study completion, up to approximately 24 months ]
    Assessment of the efficacy of each treatment arm according to RECIST 1.1. PFS: Time from date of treatment assignment until the date of objective radiological disease progression or death (by any cause in the absence of progression)
  • Duration of response (DoR) [ Time Frame: On-study tumor assessments occur every 8 weeks until week 48 and then every 12 weeks thereafter until confirmed radiological progression, death, withdrawal of consent or study completion, up to approximately 24 months ]
    Assessment of the efficacy of each treatment arm according to RECIST 1.1. DoR: Time from date of first detection of objective response until the date of objective radiological disease progression
  • Overall survival (OS) [ Time Frame: Approximately 24 months ]
    OS: Time from date of treatment assignment until the date of death by any cause
  • Blood concentration of durvalumab and novel oncology therapies [ Time Frame: From cycle 1 day 1 until cycle 7 day 1 (each cycle is 28 days) and every 12 weeks thereafter until study completion, approximately 24 months ]
    Assessment of pharmacokinetics (PK)
  • 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 (each cycle is 28 days) and every 12 weeks thereafter until study completion, approximately 24 months ]
    Investigation of the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer.
Official Title  ICMJE A Phase IB/II, 2-stage, Open-label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab (MEDI4736) in Combination With Paclitaxel and Multiple Novel Oncology Therapies and Durvalumab (MEDI4736) + Paclitaxel for First-line Metastatic Triple Negative Breast Cancer.
Brief Summary This study is designed to determine the efficacy and safety of durvalumab in combination with paclitaxel and multiple novel oncology therapies and durvalumab with paclitaxel alone for the treatment of first-line metastatic triple negative breast cancer.
Detailed Description This is a Phase IB/II, 2-stage, open-label, multicenter study to determine the efficacy and safety of durvalumab + paclitaxel + novel oncology therapies (i.e. therapies designed for immune modulation) and durvalumab + paclitaxel alone as first-line treatment in patients with metastatic triple negative breast cancer (TNBC). The study is designed to concurrently evaluate potential novel triplet combinations with clinical promise using a 2-stage approach. Part 1 is a Phase IB study of safety and initial efficacy, and Part 2 is a Phase II study. The triplet treatment regimens evaluated in Part 2 will depend on the evaluation of safety and efficacy outcomes in Part 1.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Part 1: At least 20 patients in the durvalumab-paclitaxel doublet arm and 30 patients in the durvalumab-paclitaxel-novel agent triplet arms will be enrolled in each treatment arm, for a total of approximately 110 patients (durvalumab + paclitaxel arm and 3 triplet combination arms). Additional patients may be enrolled in order to have 20 evaluable (i.e. dosed) patients per arm.

Part 2: Approximately 75 patients will be randomized to each treatment arm, for an anticipated total of at least 150 patients (durvalumab + paclitaxel arm and 1 or more triplet combination arms based on the treatment arm(s) from Part 1 that have met the protocol-defined efficacy criteria).

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Neoplasms
Intervention  ICMJE
  • Drug: Durvalumab
    Durvalumab iv Every 4 weeks (q4w)
    Other Name: MEDI4736
  • Drug: Capivasertib
    Capivasertib po bid 4-week cycles; 3 weeks on (dosing on days 2,3,4 and 5) and 1 week off
    Other Name: AZD5363
  • Drug: Danvatirsen
    Danvatirsen iv Loading doses on days 1, 3 and 5 in first cycle; Once weekly (q1w) starting at cycle 1 day 8
    Other Name: AZD9150
  • 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
Study Arms  ICMJE
  • Experimental: Arm 1
    durvalumab + paclitaxel
    Interventions:
    • Drug: Durvalumab
    • Drug: Paclitaxel
  • Experimental: Arm 2
    durvalumab + paclitaxel + capivasertib
    Interventions:
    • Drug: Durvalumab
    • Drug: Capivasertib
    • Drug: Paclitaxel
  • Experimental: Arm 4
    durvalumab + paclitaxel + danvatirsen
    Interventions:
    • Drug: Durvalumab
    • Drug: Danvatirsen
    • Drug: Paclitaxel
  • Experimental: Arm 5
    durvalumab + paclitaxel + oleclumab
    Interventions:
    • Drug: Durvalumab
    • Drug: Oleclumab
    • Drug: Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 2, 2019)
120
Original Estimated Enrollment  ICMJE
 (submitted: November 14, 2018)
100
Estimated Study Completion Date  ICMJE June 30, 2021
Estimated Primary Completion Date November 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  1. Female
  2. At least 18 years of age at the time of screening
  3. Patient must have locally confirmed 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

Exclusion criteria

  1. History of venous thromboembolism in the past 3 months
  2. Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment
  3. History of allogeneic organ transplantation
  4. Active or prior documented autoimmune or inflammatory disorders
  5. 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)
  6. Untreated CNS metastases
  7. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
  8. Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment
  9. Female patients who are pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com
Listed Location Countries  ICMJE Canada,   Korea, Republic of,   Poland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03742102
Other Study ID Numbers  ICMJE D933LC00001
2018-000764-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Peter Schmid, MD, PhD Barts Cancer Institute
PRS Account AstraZeneca
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP