NCT04841148

Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer

A Phase II Trial of Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer (PALAVY)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: Abramson Cancer Center at Penn Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical trial will assess the safety and early efficacy of Hydroxychloroquine or Avelumab, with or without Palbociclib, in early-stage ER+ breast cancer patients who are found to harbor disseminated tumor cells (DTCs) in the bone marrow after definitive surgery and standard adjuvant therapy.

Detailed description

The overarching goal of this clinical trial is to reduce the incidence of incurable recurrent metastatic breast cancer by targeting the precursors of these recurrences, bone marrow disseminated tumor cells (DTCs) present after definitive treatment. This trial targets unique mechanisms by which DTCs maintain a dormant phenotype (autophagy) and by which they escape dormancy (upregulation of the cyclin-dependent kinase4/6 (CDK4/6) pathway and microenvironmental factors such as immune evasion). The selection of these agents is based upon strong preclinical data demonstrating the relevance of autophagy (inhibited by HCQ), the CDK4/6 pathway (inhibited by palbociclib) and the programmed cell death-1 (PD-1)/Programmed death-ligand 1 (PD-L1) immune checkpoint pathway (blocked by avelumab) as critical mechanisms of cellular and immunological tumor dormancy. The phase II trial is designed to provide "proof of concept" and estimates of effect of various combinations and durations of these therapies on bone marrow DTCs as a surrogate for ultimate reduction in recurrence. The correlative science aims will provide additional insight into the relationship between the primary tumor and both the biology of DTCs and host immune surveillance for target validation and development, as well as evaluate the role of additional biomarkers both in the bone marrow (with a novel flow-based assay), and in the peripheral circulation (including both circulating tumor cells and cell-free DNA), to identify patients with minimal residual disease (MRD) and targets for intervention and measurement of DTC response.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	HCQ	600 mg tablets twice daily D1-28 of each 28-day cycle
DRUG	Avelumab	10 mg/kg, IV, D1 and D15 of each 28-day cycle
DRUG	Palbociclib	125 mg capsule daily, by mouth on D1-21 concurrently with Avelumab. Or 75 mg capsule daily, by mouth on D1-28 concurrently with HCQ.

Timeline

• Start date: 2021-06-01
• Primary completion: 2027-07-01
• Completion: 2028-05-01
• First posted: 2021-04-12
• Last updated: 2026-04-09

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study