Clinical Trials /

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

NCT03032406

Description:

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.

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: UPCC 24116
  • NCT ID: NCT03032406

Conditions

  • Breast Cancer Stage IIB

Interventions

DrugSynonymsArms
HydroxychloroquineHCQ alone (Arm A)
EverolimusEVE alone (Arm B)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
HCQ alone (Arm A)Experimental
  • Hydroxychloroquine
EVE alone (Arm B)Experimental
  • Everolimus
combination HCQ and EVE (Arm C)Experimental
  • Hydroxychloroquine
  • Everolimus
observation (Arm D)Experimental
  • Hydroxychloroquine
  • Everolimus

Eligibility Criteria

        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.)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Adverse Events
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

October 8, 2019