Clinical trial NCT04818632: AZD9833 China PK Study
Official title: A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination With Palbociclib or Everolimus in Chinese Patients With Oestrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (mBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: ER+, HER2-, Metastatic Breast Cancer
Keywords: Breast Cancer
Open-label
Phase 1
Safety
Tolerability
Pharmacokinetics
ER Positive
HER2 Negative
Metastatic Breast Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-03-26
Enrollment: 28
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Detailed description: This study is designed to investigate and characterize the safety, tolerability and PK of AZD9833 monotherapy (Part A, Part B-cohort 1) or in combination with palbociclib (optional Part B cohort 2) or everolimus (optional Part B cohort 3) and to explore the preliminary anti-tumour activity in Chinese patients

Eligibility criteria: Inclusion Criteria:

1. Any menopausal status:

   1. 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.
   2. Post-menopausal defined according to standard criteria in the protocol.
2. Histological or cytological confirmation of adenocarcinoma of the breast.
3. Documented positive ER status and HER2 negative status of primary or metastatic tumour tissue.
4. ECOG performance status 0 to 1.
5. Metastatic disease and radiological or objective evidence of progression on or after the last systemic therapy prior to the start of study intervention.
6. 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.
7. Recurrence or progression on at least one line of endocrine therapy in the metastatic disease setting.
8. For Part A and Part B cohort 1, patients should be eligible for SERD monotherapy treatment.
9. 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.
10. For Part B Cohort 3, patients should be eligible for SERD treatment and mTOR inhibitors, and prior treatment with mTOR inhibitors is not permitted.

Exclusion Criteria:

1. Previous treatment with AZD9833.
2. Presence of life-threatening metastatic visceral disease, uncontrolled CNS metastatic disease or life-threatening extensive hepatic involvement.
3. 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.
4. Inadequate bone marrow reserve or organ function.
5. Any clinically important and symptomatic heart disease.
6. Any concurrent anti-cancer treatment.
7. 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.

Primary outcomes:
measure: The number of subjects with dose-limiting toxicity, as defined in the protocol.
timeFrame: Minimum observation period 28 days on treatment.
measure: The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
timeFrame: 6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention
measure: Plasma AZD9833 concentrations and derived PK parameters.
timeFrame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
Secondary outcomes:
measure: The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
timeFrame: 6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention
measure: 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).
timeFrame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
measure: Objective Response Rate
timeFrame: 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)
measure: Duration of Response
timeFrame: 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)
measure: Clinical benefit rate at 24 weeks
timeFrame: Up to 24 weeks
measure: Percentage Change in Tumour Size
timeFrame: 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)
measure: Progression Free Survival
timeFrame: From start of treatment to disease progression/latest date of evaluable RECIST assessment (approximate 1 year)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
Study officials:
affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center
name: Jiong Wu
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center
name: Jian Zhang
role: PRINCIPAL_INVESTIGATOR
References: