Hydroxychloroquine, Abemaciclib and Endocrine Therapy in Hormone Receptor Positive (HR+)/Her 2 Negative Breast Cancer

Phase 1

Withdrawn

• Conditions: Solid Tumor; Advanced Breast Cancer
• Interventions: Drug: Abemaciclib; Drug: Hydroxychloroquine 400 mg; Drug: Hydroxychloroquine 600 mg; Drug: Hydroxychloroquine 200 mg; Drug: Faslodex; Drug: Anastrazole; Drug: Letrozole

• Registration Number: NCT04316169
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

The hypothesis is that abemaciclib synergizes with autophagy inhibitor hydroxychloroquine (HCQ/ Plaquenil), inducing apoptosis leading to tumor regression.

Detailed Description

Part 1: 3+3 dose escalation of HCQ combined with abemaciclib in advanced solid tumors.

Part 2: HCQ at top-dose level from part one is combined with abemaciclib and endocrine therapy in HR+/Her 2- advanced breast cancer (ABC) and divided into two cohorts based on prior exposure to endocrine therapy.

Primary Objective

1. Dose-escalation cohort: To determine safety and tolerability of HCQ combined with abemaciclib.

2. Dose-expansion cohort: To determine safety and tolerability of HCQ combined with abemaciclib and endocrine therapy in HR+/Her2- ABC.

Secondary Objectives

1. To assess the clinical efficacy of HCQ in combination with abemaciclib and hormone blockade in the dose- expansion cohort of advanced ER- positive breast cancer participants.

2. To assess the clinical efficacy of HCQ in combination with abemaciclib in the dose- escalation cohort

Study Timeline

• Study First Submitted: 2020-03-18
• Study First Submitted QC: 2020-03-18
• Study First Posted: 2020-03-20
• Study Start: 2021-10-21
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-21
• Last Update Posted: 2022-12-23
• Primary Completion: 2027-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Abemaciclib and HCQ 400 mg b.i.d.	Hydroxychloroquine 400 mg	HCQ will have a dose escalation of a 3 + 3 design.
Abemaciclib and HCQ 600 mg b.i.d.	Hydroxychloroquine 600 mg	HCQ will have a dose escalation of a 3 + 3 design.
Abemaciclib and HCQ 200 mg b.i.d.	Abemaciclib	HCQ will have a dose escalation of a 3 + 3 design.
Abemaciclib and HCQ 600 mg b.i.d.	Abemaciclib	HCQ will have a dose escalation of a 3 + 3 design.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Abemaciclib	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Anastrazole	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Hydroxychloroquine 600 mg	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib and HCQ 200 mg b.i.d.	Hydroxychloroquine 200 mg	HCQ will have a dose escalation of a 3 + 3 design.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Hydroxychloroquine 200 mg	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Hydroxychloroquine 400 mg	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Faslodex	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib + HCQ (Optimal Dose) + endocrine therapy	Letrozole	This group will be divided into two cohorts: 1. eligible participants who are endocrine therapy naive. 2. eligible participants who had one prior line of endocrine therapy.
Abemaciclib and HCQ 400 mg b.i.d.	Abemaciclib	HCQ will have a dose escalation of a 3 + 3 design.

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicities during dose-escalation phase.	28 days for each cohort	The number of participants with dose-limiting toxicities during the dose-escalation phase (HCQ in combination with abemaciclib).
Dose-limiting toxicities in dose-expansion phase.	28 days for each cohort	The number of participants with dose-limiting toxicities during the dose-expansion phase (maximum-tolerated dose of HCQ and abemaciclib in combination with endocrine therapy.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival.	1 Year	This measure is the number of months participants remain free from evidence of disease. Participants will undergo imaging every eight weeks and results will be reported annually.
Overall response rate.	1 Year	The number of participants who have a partial or complete response based on tumor measurement by CT or MRI using RECIST 1.1. Participants will be imaged every eight weeks and reported annually.

Trial Locations

Locations (1)

Froedtert Hospital and the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States