AZD9833 China PK Study

NCT04818632 | Completed Phase 1

• 1 other identifier: D8530C00007
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 4

Brief Summary

A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Chinese patients with ER Positive, HER2 Negative, Metastatic Breast Cancer

Conditions

ER+, HER2-, Metastatic Breast Cancer

Keywords

Breast Cancer; Open-label; Phase 1; Safety; Tolerability; Pharmacokinetics; ER Positive; HER2 Negative; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (3)

• The number of subjects with dose-limiting toxicity, as defined in the protocol.

  Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria of AZD9833 monotherapy. \[part A only\]

  Minimum observation period 28 days on treatment.

• The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.

  Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v5.0 of AZD9833 monotherapy.

  6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention

• Plasma AZD9833 concentrations and derived PK parameters.

  To characterise the single- and multiple-dose PK of AZD9833 monotherapy.

  At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )

Secondary Outcomes (7)

• The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.

  6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention

• Plasma AZD9833 concentrations and derived PK parameters (for optional expansion cohorts Part B Cohorts 2 and 3 only). Everolimus (whole blood) concentrations and derived PK parameters (for optional expansion cohort Part B Cohort 3 only).

  At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )

• Objective Response Rate

  Week 8 and week 16 and week 24 and then every 12 weeks (week 36, 48, 60) until the end of the study (approximately 1 year)

• Duration of Response

  Week 8 and week 16 and week 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year)

• Clinical benefit rate at 24 weeks

  Up to 24 weeks

Study Arms (4)

AZD9833 monotherapy dose escalation

EXPERIMENTAL

Drug: AZD9833

AZD9833 monotherapy dose expansion

EXPERIMENTAL

Drug: AZD9833

AZD9833 with palbociclib dose expansion

EXPERIMENTAL

Drug: AZD9833 with palbociclib

AZD9833 with everolimus dose expansion

EXPERIMENTAL

Drug: AZD9833 with everolimus

Interventions

AZD9833 DRUG

Part A: AZD9833 monotherapy dose escalation.

AZD9833 monotherapy dose escalation

AZD9833 with palbociclib DRUG

Part B: AZD9833 with palbociclib dose expansion

AZD9833 with palbociclib dose expansion

AZD9833 with everolimus DRUG

Part B: AZD9833 with everolimus dose expansion

AZD9833 with everolimus dose expansion

Eligibility Criteria

• Age: 18 Years - 130 Years
• Gender Eligibility Details: Pre-menopausal or Post-menopausal women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any menopausal status:
• Pre-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to the start of study intervention and must be willing to continue to receive LHRH agonist therapy for the duration of the study.
• Post-menopausal defined according to standard criteria in the protocol.
• Histological or cytological confirmation of adenocarcinoma of the breast.
• Documented positive ER status and HER2 negative status of primary or metastatic tumour tissue.
• ECOG performance status 0 to 1.
• Metastatic disease and radiological or objective evidence of progression on or after the last systemic therapy prior to the start of study intervention.
• At least one lesion as per RECIST Version 1.1 that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, or plain X-ray or clinical examination.
• Recurrence or progression on at least one line of endocrine therapy in the metastatic disease setting.
• For Part A and Part B cohort 1, patients should be eligible for SERD monotherapy treatment.
• For Part B Cohort 2, patients should be eligible for SERD treatment and CDK4/6 inhibitors, and prior treatment with CDK4/6 inhibitors is not permitted.
• For Part B Cohort 3, patients should be eligible for SERD treatment and mTOR inhibitors, and prior treatment with mTOR inhibitors is not permitted.

You may not qualify if:

• Previous treatment with AZD9833.
• Presence of life-threatening metastatic visceral disease, uncontrolled CNS metastatic disease or life-threatening extensive hepatic involvement.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or infection requiring intravenous antibiotic therapy, which makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol.
• Inadequate bone marrow reserve or organ function.
• Any clinically important and symptomatic heart disease.
• Any concurrent anti-cancer treatment.
• Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833 (and palbociclib and everolimus).
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Beijing, 100142, China

Location

Research Site

Chengdu, 610041, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Wuhan, 430022, China

Location

Related Links

• AstraZenecaClinicaltrials.com

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833; palbociclib; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jiong Wu

  Department of Breast Surgery, Fudan University Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

• Jian Zhang

  Department of Medical Oncology, Fudan University Shanghai Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: March 26, 2021
• Study Start: November 12, 2021
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: December 17, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

CN (4)