CLEVER Study

A Phase II Pilot Trial of HydroxyChLoroquine, EVErolimus or the Combination for Prevention of Recurrent Breast Cancer

The goal of the CLEVER Trial and the overall TCE recurrence prevention effort is to prevent breast cancer recurrence by providing additional targeted therapy to patients most at risk for relapse. In this research, patients most at risk for relapse were identified as those who test positive for disseminated tumor cells (DTC) in the bone marrow. DTCs are the cells that are thought to survive primary therapy, travel to the bone marrow where they can remain in a dormant state for years, and then potentially give rise to a recurrence. Importantly, the biological properties of DTCs are quite different than those of the original tumor. Patients who had completed all of their primary treatment (ie surgery, chemotherapy, radiation) and met eligibility criteria underwent this bone marrow evaluation by enrolling on the PENN-SURMOUNT screening study.

Patients with a positive bone marrow DTC test were then offered the opportunity to participate in CLEVER, which used oral medications to target the unique properties of the DTCs with the goal of eliminating these cells from the bone marrow. Specifically, the CLEVER trial evaluated the feasibility and biological impact of administering hydroxychloroquine (HCQ), everolimus (EVE), or the combination in patients who have DTCs and meet all eligibility requirements.

Patients enrolled in CLEVER were randomized to one of the four (4) study arms.

• Participants on Arm A took hydroxychloroquine twice a day for 6 months (24 weeks)
• Participants on Arm B took everolimus daily for 6 months (24 weeks)
• Participants on Arm C took  hydroxychloroquine twice a day and everolimus daily for 6 months (24 weeks)
• Participants on Arm D were followed by the study staff without receiving treatment for the first 3 months, and then will start treatment with hydroxychloroquine twice a day and everolimus daily for 6 months (24 weeks)

During the course of the CLEVER trial, patients underwent additional bone marrow assessments at 3 and 6 months. Patients who continued to have a positive bone marrow DTC test after 6 months were offered the opportunity to continue on combination therapy for an additional 6 months. If the patient continued on combination therapy, there was a final bone marrow assessment after 12 months. Patients will continue to be followed in the clinic for up to 3 years after completion of study treatment.

Trial results are being analyzed and will be made publicly available in the near future.