Clinical Trials /

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

NCT03742102

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer.
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: D933LC00001
  • SECONDARY ID: 2018-000764-29
  • NCT ID: NCT03742102

Conditions

  • Triple Negative Breast Neoplasms

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Arm 1
SelumetinibAZD6244Arm 3
CapivasertibAZD5363Arm 2
DanvatirsenAZD9150Arm 4
OleclumabMEDI9447Arm 5
PaclitaxelArm 1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1Experimentaldurvalumab + paclitaxel
  • Durvalumab
  • Paclitaxel
Arm 2Experimentaldurvalumab + daclitaxel + capivasertib
  • Durvalumab
  • Capivasertib
  • Paclitaxel
Arm 3Experimentaldurvalumab + paclitaxel + selumetinib
  • Durvalumab
  • Selumetinib
  • Paclitaxel
Arm 4Experimentaldurvalumab + paclitaxel + danvatirsen
  • Durvalumab
  • Danvatirsen
  • Paclitaxel
Arm 5Experimentaldurvalumab + paclitaxel + oleclumab
  • Durvalumab
  • Oleclumab
  • Paclitaxel

Eligibility 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

          7. Life expectancy of at least 12 weeks

        Exclusion criteria

          1. History of venous thromboembolism in the past 6 months

          2. Diagnosis of diabetes mellitus type 1, poorly controlled diabetes mellitus type 2 or
             diabetes requiring insulin

          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, 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
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:From informed consent until the safety follow-up visit 3 months after the last dose of study drug
Safety Issue:
Description:Assessment of safety and tolerability of each treatment arm

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Approximately 24 months
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description: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)
Measure: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
Safety Issue:
Description: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
Measure:Overall survival (OS)
Time Frame:Approximately 24 months
Safety Issue:
Description:OS: Time from date of treatment assignment until the date of death by any cause
Measure: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
Safety Issue:
Description:Assessment of pharmacokinetics (PK)
Measure: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
Safety Issue:
Description:Investigation of the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • 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

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