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DZD1516 in Combination With Trastuzumab and Capecitabine, or in Combination With T-DM1, in Patients With Metastatic HER2 Positive Breast Cancer

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ClinicalTrials.gov Identifier: NCT04509596
Recruitment Status : Recruiting
First Posted : August 12, 2020
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Dizal Pharmaceuticals

Brief Summary:
DZD1516 is an oral, blood brain barrier penetrable, selective HER2 tyrosine kinase inhibitor. This study is designed to evaluate the safety and tolerability of DZD1516 in patients with metastatic HER2 positive breast cancer who have progressed following prior therapy. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment. It will also measure the levels of drug in the body and assess its anti-cancer activity as monotherapy and in combination with trastuzumab and/or capecitabine, or in combination with T-DM1

Condition or disease Intervention/treatment Phase
Breast Cancer Metastatic Drug: DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of DZD1516 in Combination With Trastuzumab and Capecitabine, or DZD1516 in Combination With T-DM1, in Patients With Metastatic HER2 Positive (HER2+) Breast Cancer
Actual Study Start Date : September 21, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: daily dose of DZD1516
daily dose of DZD1516
Drug: DZD1516 mono therapy in Part A, DZD1516 in combination with trastuzumab and/or capecitabine in Part B, DZD1516 in combination with T-DM1 in Part C

Part A is twice daily (except Cycle 0) oral dosing of DZD1516, starting from 50 mg. If tolerated, dose will be escalated in subsequent cohorts until MTD.

Part B is twice daily oral dosing of DZD1516 in combination with capecitabine 1000 mg/m2 orally twice daily on Days 1-14 of each 21-day cycle or with trastuzumab 8 mg/kg intravenously (IV) on Day 1 of Cycle 1, followed by 6 mg/kg on Day 1 of each 21-day cycle.

Part C is twice daily oral dosing of DZD1516 in combination with T-DM1 3.6 mg/kg intravenously (IV) once every 21 days





Primary Outcome Measures :
  1. Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: up to approximately 1 year ]
    To investigate the safety and tolerability of DZD1516

  2. Incidence of dose limiting toxicities (DLTs) [ Time Frame: 21 days after the first multiple dose ]
    To investigate the safety and tolerability of DZD1516

  3. To define maximum tolerated dose (MTD) of DZD1516 if possible (Part A only) [ Time Frame: 21 days after the first multiple dose ]
    To investigate the safety and tolerability of DZD1516

  4. To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with trastuzumab and capecitabine (Part B only) [ Time Frame: 21 days after the first multiple dose ]
    To investigate the safety and tolerability of DZD1516 in combination with either trastuzumab, capecitabine, or both trastuzumab and capecitabine

  5. To define Recommended Phase II Combination Dose (RP2CD) of DZD1516 in combination with T-DM1 (Part C only) [ Time Frame: 21 days after the first multiple dose ]
    To investigate the safety and tolerability of DZD1516 in combination with T-DM1


Secondary Outcome Measures :
  1. Drug concentrations of DZD1516 and its metabolite DZ2678 in plasma, urine and CSF [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  2. Maximum plasma concentration (Cmax) of DZD1516 and its metabolite DZ2678 [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  3. Area under the plasma concentration-time curve (AUC) of DZD1516 and its metabolite DZ2678 [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  4. Plasma concentration of capecitabine and metabolites 5-FU (Part B only) [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  5. Plasma Cmax of capecitabine and 5-FU (Part B only) [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  6. Plasma AUC of capecitabine and 5-FU (Part B only) [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  7. Plasma concentration of DM1 (Part C only) [ Time Frame: up to approximately 6 months ]
    Pharmacokinetics endpoints

  8. Objective Response Rate (ORR) [ Time Frame: up to approximately 1 year ]
    To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy

  9. Disease Control Rate (DCR) [ Time Frame: up to approximately 1 year ]
    To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy

  10. Duration of Response (DoR) [ Time Frame: up to approximately 1 year ]
    To assess preliminary anti-tumor efficacy of DZD1516 as monotherapy and as combination therapy

  11. Progression free survival (PFS) (Part B and Part C on) [ Time Frame: up to approximately 1 year ]
    To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy

  12. Overall survival (for patients with leptomeningeal metastasis in Part B and Part C only) [ Time Frame: up to approximately 1 year ]
    To assess preliminary anti-tumor efficacy of DZD1516 as combination therapy



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent.
  • Male or female patients aged ≥ 18 years
  • histologically or cytologically confirmed HER2 positive advanced breast cancer which failed prior therapies
  • Predicted life expectancy ≥ 12 weeks.
  • ECOG performance status 0 to 1 for patients without LM, and 0 to 2 for patients with LM at the time of signing ICF
  • Adequate bone marrow reserve and organ system functions
  • For patients without CNS metastases, patients must have at least one measurable lesion according to RECIST (version 1.1)
  • For patients with Brain metastasis: Patient must have at least one measurable intracranial lesion according to modified RECIST 1.1

Exclusion Criteria:

  • Intervention with any of the following: Any investigational agents or study drugs from a previous clinical study within 4 weeks of the first dose of study treatment; Any cytotoxic chemotherapy or other anticancer drugs for the treatment of metastatic breast cancer from a previous treatment regimen within 4 weeks of the first dose of study treatment; Any intrathecal chemotherapy within 2 weeks of the first dose of study treatment;Major surgery procedure (excluding placement of vascular access), or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study; Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment;
  • CNS complications that require urgent neurosurgical intervention
  • Any evidence of severe or uncontrolled systemic diseases
  • Another malignancy within 5 years prior to enrolment with the exception of adequately treated in-situ carcinoma of the cervix, uterus, basal or squamous cell carcinoma or non-melanomatous skin cancer.
  • Live vaccines within 4 weeks prior to first dose.
  • Active infections including:Tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice);Positive Hepatitis B surface antigen (HBsAg) or positive HCV antibodies or confirmed positive HIV test result.
  • Refractory nausea and vomiting if not controlled by supportive therapy, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of DZD1516
  • Involvement in the planning and conduct of the study (applies to Sponsor staff or staff at the study site).
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.

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): NCT04509596


Contacts
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Contact: Grace Yu, PhD 86-21-61095854 grace.yu@dizalpharma.com
Contact: Pamela Yang, M.D & Ph. D 86-21-61097866 pamela.yang@dizalpharma.com

Locations
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United States, California
UCLA Hematology/Oncology Parkside Recruiting
Santa Monica, California, United States, 90404
Contact: McAndrew    310-829-5471    NMcAndrew@mednet.ucla.edu   
China
Zhejiang Cancer Hospital Recruiting
Hangzhou, China
Contact: Wang    86-0571-88122222    Wxj88851@yahoo.com   
Cancer Hospital, Fudan University Recruiting
Shanghai, China
Contact: Hu    86-021-64175590    xchu2009@hotmail.com   
Sponsors and Collaborators
Dizal Pharmaceuticals
Investigators
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Principal Investigator: McAndrew UCLA Hematology/Oncology Parkside
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Responsible Party: Dizal Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04509596    
Other Study ID Numbers: DZ2019HE001
First Posted: August 12, 2020    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Trastuzumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological