Phase 2
Completed N=71
A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer
Source: ClinicalTrials.gov NCT01216176 ↗Enrolled (actual)
71
Serious AEs
12.7%
Results posted
Jul 2019
Primary outcomePrimary: Phase I Cohort A: Maximum Tolerated AZD0530 Daily Dose Used in Combination With Daily Oral Anastrozole — 1; 175 mg/day oral dose
Summary
The investigators propose to conduct a Phase I/randomized Phase II study design in order to test the tolerability and efficacy of AZD0530 (also called saracatinib) when used together with anastrozole in therapy for ER+ and/or PR+, postmenopausal breast cancer. The Phase I pharmacokinetic (PK) cohort of the study (cohort A) in postmenopausal women with metastatic breast cancer 2008-2009 showed initial safety,tolerability and good bioavailability of both drugs and determined the doses for use in the ongoing Phase II trial. In the randomized Phase II cohort of the study (cohort B), postmenopausal women with newly diagnosed, previously untreated ER+, HER2 negative breast cancer that is at least 2 cm or more in diameter by clinical exam or radiology will be randomized to either neoadjuvant treatment with anastrozole plus placebo, or anastrozole in combination with AZD0530 (saracatinib). The Phase II cohort will permit extended assays of tolerability, initial estimates of efficacy, and the investigation of molecular predictors of drug efficacy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase I Cohort A: Maximum Tolerated AZD0530 Daily Dose Used in Combination With Daily Oral Anastrozole |
1; 175 | — |
| PRIMARY Phase II - Cohort B: Compare Treatment Groups (AZD0530 + Anastrozole Versus Anastrozole With Placebo) With Respect to Clinical Response |
-61.5; -62.3; -87.9; -90.7 | — |
| SECONDARY Phase I - Cohort A: Plasma Concentrations of AZD0530 (Saracatinib) and Anastrozole |
0; 127.47; 79.1; 46.17; 91.33; 125.49 | — |
| SECONDARY Phase 1-Cohort A: Peak Concentration of Each Study Drug ( AZD0530 (Saracatinib) and Anastrozole) |
271.97; 47.33 | — |
| SECONDARY Phase II Cohort B: Change in Tumor Size by Comparison of Serial MRI |
-26.9; -15.9; -46.4; -35.0; -44.6; -22.5 | — |
| SECONDARY Phase II - Cohort B: Number of Participants With Pathologic Complete Response (pCR) |
0; 0 | — |
| SECONDARY Phase II - Cohort B: The Number of Participants Achieving Clinical Benefit Defined as Complete Response (CR), or Partial Response (PR) or Stable Disease (SD) |
0; 0; 16; 17; 0; 0 | — |
| SECONDARY Phase II - Cohort B: To Report the Pharmacokinetics (Mean Blood Levels of Drug) of AZD0530 (Saracatinib) and Anastrozole |
52.7; 37.4; 49.9; 37.6; 48.3; 39.5 | — |
| SECONDARY Phase II - Cohort B: Treatment Emergent Adverse Events Associated With AZD0530 (Saracatinib) Given With Anastrozole and of Anastrozole Given With Placebo |
7; 1; 4; 1; 3; 0 | — |
Eligibility Criteria
Inclusion Criteria - Phase 1 (Cohort A):
- Female patient ≥ 18 years
- Patient must be postmenopausal, verified by 1 of the following:
- Bilateral surgical oophorectomy
- No spontaneous menses > 1 year
- No menses for 150/100], history of myocardial infarction or stroke within 6 months, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- Active, uncontrolled infection requiring parenteral antimicrobials
- A history of a severe hypersensitivity reaction to anastrozole, or AZD0530 or their excipients
- Evidence of bleeding diathesis or coagulopathy.
- Resting EKG with measurable QTc interval of >480msec at 2 or more time points within a 24 hr period.
- Since AZD0530 is a substrate and inhibitor of CYP3A4, patients requiring medication with drugs listed in Appendix XI should be excluded from study.
- Any evidence of severe or uncontrolled systemic medical or psychiatric conditions (e.g. Severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]) or current unstable or uncompensated respiratory or cardiac conditions which make it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
- Evidence of underlying pulmonary dysfunction as evidenced by oxygen saturation 480msec at 2 or more time points within a 24 hr period.
- AZD0530 (saracatinib) is a substrate and inhibitor of CYP3A4. Since concurrent administration of AZD0530 with other CYP3A4 substrates has been shown to be well tolerated, continuation or initiation of medically indicated drugs that are substrates of CYP3A4 is permitted at MD discretion. Drugs listed in Appendix X that are known to strongly induce or inhibit CYP3A4 activity should be discontinued prior to study entry and should not be initiated during protocol treatment.
- Any evidence of severe or uncontrolled systemic psychiatric or medical conditions (eg. Severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]) or current unstable or uncompensated respiratory or cardiac conditions which make it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol
- Evidence of underlying pulmonary dysfunction as evidenced by oxygen saturation <90% by pulse oximetry prior to study entry and/or symptomatic pulmonary (pleural or parenchymal) disease.
- Subjects unwilling or unable to undergo breast MRI as required by protocol will be excluded from study
Data sourced from ClinicalTrials.gov (NCT01216176). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.