Estradiol Plus Olaparib for Breast Cancer (PHOEBE)

Metastatic Breast Cancer Clinical Trial

— PHOEBE  

Official title:

Phase 1b Study of Olaparib and Estradiol in Advanced ER+ Breast Cancer (PHOEBE)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05900895
• Other study ID #: STUDY02002007
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2024
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: Dartmouth-Hitchcock Medical Center
• Contact: Research Nurse
• Phone: 1-800-639-6918
• Email: Cancer.Research.Nurse[@]dartmouth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Determine the safety and recommended Phase II dose of olaparib in combination with 17b-estradiol in post-menopausal patients with advanced ER+/HER2- breast cancer.

Description:

Patients with endocrine-resistant ER+/HER2- breast cancer are eligible. Patients will be treated with the combination of 17b-estradiol and olaparib for 2 cycles, and then treated with single-agent 17b-estradiol until disease progression. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: December 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Post-menopausal women with ER+/HER2- breast cancer.

• Metastatic or locoregional recurrence not amenable to treatment with curative intent.

• Received =1 prior line of endocrine-based therapy in the advanced/metastatic setting.

Exclusion Criteria:

• During study treatment, no concurrent anti-cancer therapies are allowed with the following exceptions:

o Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) permitted.

• Any investigational cancer therapy or systemic chemotherapy in the last 3 weeks.

• Any radiation therapy in the last 2 weeks.

• Known CNS disease, unless clinically stable for = 3 months.

• Concomitant use of known strong or moderate CYP3A inhibitors.

• Persistent toxicities (=CTCAE grade 2) caused by previous cancer therapy.

• History of any of the following:

• Deep venous thrombosis

• Pulmonary embolism

• Stroke

• Acute myocardial infarction

• Congestive heart failure

• Previous malignancy not treated with curative intent, or with an estimated recurrence risk =30%

• Severe renal impairment (creatinine clearance = 30 mL/min).

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Olaparib
Participants will be treated with olaparib at the approved doses for the treatment of subtypes of breast cancer or at reduced dose/frequency for participants with moderate renal impairment.
• 17b-estradiol
17b-estradiol will be taken orally three times per day.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mary D Chamberlin	Dartmouth-Hitchcock Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the Phase II dose of olaparib in combination with 17b-estradiol	Determine the safety and recommended Phase II dose of olaparib in combination with 17b-estradiol in post-menopausal patients with advanced ER+/HER2- breast cancer.	8 weeks
Secondary	Clinical benefit rate	The proportion of evaluable patients experiencing clinical benefit (stable disease at 24 weeks, complete or partial response per RECIST) will be measured.	6 months
Secondary	Objective response rate	The proportion of evaluable patients experiencing objective response (complete or partial response per RECIST) will be measured.	6 months
Secondary	Progression-free survival	Progression-free survival will be measured by measuring the length of time between the start of study treatment until the time of cancer progression or death from any cause.	12 months
Secondary	Plasma Olaparib concentration	The concentration of Olaparib in plasma will be measured over 6 hours.	6 hours
Secondary	Plasma 17b-Estradiol/Estrone concentration	The concentration of 17b-Estradiol/Estrone in plasma will be measured over 6 hours.	6 hours