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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03032406
Recruitment Status : Recruiting
First Posted : January 26, 2017
Last Update Posted : August 5, 2020
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Brief Summary:
To evaluate the feasibility of administering HCQ, EVE or the combination in patients who have completed primary therapy for breast cancer and harbor bone marrow disseminated tumor cells.

Condition or disease Intervention/treatment Phase
Breast Cancer Stage IIB Drug: Hydroxychloroquine Drug: Everolimus Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CLEVER Pilot Trial: A Phase II Pilot Trial of HydroxyChLoroquine, EVErolimus or the Combination for Prevention of Recurrent Breast Cancer
Actual Study Start Date : January 23, 2017
Estimated Primary Completion Date : January 23, 2022
Estimated Study Completion Date : January 23, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: HCQ alone (Arm A) Drug: Hydroxychloroquine

Experimental: EVE alone (Arm B) Drug: Everolimus

Experimental: combination HCQ and EVE (Arm C) Drug: Hydroxychloroquine

Drug: Everolimus

Experimental: observation (Arm D) Drug: Hydroxychloroquine

Drug: Everolimus

Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically-confirmed, primary, invasive breast cancer diagnosed within 5 years of study entry.
  • Qualifying risk status, at diagnosis utilizing receptor testing by

ASCO/CAP guidelines, meeting one of the following:

  • Histologically positive axillary lymph nodes
  • Primary tumor that is ER/PR/Her2 negative
  • Primary tumor that is ER+/Her2 negative/Lymph node negative with Breast Cancer Recurrence Score of ≥ 25 per the Genomic Health Oncotype DX breast cancer test
  • Evidence of residual disease in the breast on pathological assessment after neoadjuvant chemotherapy.
  • Patients must have completed all primary therapy (definitive surgery, (neo)adjuvant chemotherapy adjuvant radiation and/or Her2-directed therapy) for the index malignancy at least 4 weeks prior to study entry. All prior treatment-related toxicity must be resolved prior to study enrollment. Concurrent receipt of adjuvant endocrine and bone modifying agents is allowed per standard of care guidelines.
  • Bone marrow aspirate after completion of therapy demonstrates detectable DTCs (via IHC)
  • No evidence of recurrent local or distant breast cancer by physical examination, blood tests (CBC, LFTs, Alk Phos), or symptom-directed imaging, per NCCN guidelines.
  • Age ≥ 18 years
  • ECOG performance status 2
  • No contraindications to the study medications or uncontrolled medical illness.
  • Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL
  • Adequate liver function as shown by: Serum bilirubin ≤ 1.5 x ULN, ALT and AST ≤ 2.5 x ULN, and INR ≤1.5
  • Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of anticoagulant for >2 weeks at time of randomization. For patients on therapeutic anti-coagulants, medication must be clinically held peri-procedure (bone marrow aspirate) per standard clinical management.
  • Adequate renal function: serum creatinine ≤ 2.0 x ULN or creatinine clearance (CrCl) ≥ 30mL/min obtained within 28 days prior to registration. A calculated creatinine clearance by Cockcroft-Gault Formula is acceptable in lieu of a measured value.
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
  • Ability to provide informed consent

Exclusion criteria

  • Concurrent enrollment on another investigational therapy
  • Prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
  • Known hypersensitivity to Everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients.
  • Patients receiving chronic, high dose systemic treatment with corticosteroids defined as: chronic use of cortisone >50mg; hydrocortisone >40mg, prednisone >10mg, methylprednisone >8mg or dexamethasone > 1.5mg; or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study including: Symptomatic congestive heart failure of New York heart Association Class III or IV Unstable angina pectoris, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease Severely impaired lung function with a previously documented spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN Active (acute or chronic) or uncontrolled severe infections Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis A known history of HIV seropositivity as reported by the patient Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of EVE (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) Patients with an active, bleeding diathesis Active or latent, untreated Hepatitis B or C. A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial and for 8 weeks after stopping study drug, by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of EVE.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03032406

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Contact: Angela DeMichele, MD 855-216-0098

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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Angela DeMichele, MD    855-216-0098   
Principal Investigator: Angela DeMichele, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
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Principal Investigator: Angela DeMichele, MD Abramson Cancer Center of the University of Pennsylvania
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Responsible Party: Abramson Cancer Center of the University of Pennsylvania Identifier: NCT03032406    
Other Study ID Numbers: UPCC 24116
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: August 5, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents