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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 : August 30, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Triple Negative Breast Neoplasms Drug: Durvalumab Drug: Capivasertib Drug: Danvatirsen Drug: Oleclumab Drug: Paclitaxel 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 + 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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
Official Title: 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.
Actual Study Start Date : December 21, 2018
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Arm 1
durvalumab + paclitaxel
Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w)
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)
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: Paclitaxel
Paclitaxel iv 4-week cycles: 3 weeks once weekly (q1w) and 1 week off

Experimental: Arm 4
durvalumab + paclitaxel + danvatirsen
Drug: Durvalumab
Durvalumab iv Every 4 weeks (q4w)
Other Name: MEDI4736

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: 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)
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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. 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

  4. Overall survival (OS) [ Time Frame: Approximately 24 months ]
    OS: Time from date of treatment assignment until the date of death by any cause

  5. 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)

  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 (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



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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 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

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: AstraZeneca Cancer Study Locator Service 1-877-400-4656 AstraZeneca@emergingmed.com

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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Peter Schmid, MD, PhD Barts Cancer Institute

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03742102     History of Changes
Other Study ID Numbers: D933LC00001
2018-000764-29 ( EudraCT Number )
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: August 2019

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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
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
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms
Neoplasms by Site
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