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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HCQ alone (Arm A) | Experimental |
| |
| EVE alone (Arm B) | Experimental |
| |
| combination HCQ and EVE (Arm C+D) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydroxychloroquine | Drug | Hydroxychloroquine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility: Number of Participants Who Completed 6 Cycles of Protocol Treatment Without Grade 3 or 4 Toxicity | For the primary endpoint of feasibility, we employed ongoing Bayesian toxicity monitoring after every 3 participants completed cycle 6, assuming a Beta (1,2) prior, equivalent to one DLT observed in 3 treated participants. Early termination of a treatment arm for toxicity (non-feasibility) would occur if the posterior probability that the toxicity rate exceeds the target maximum of 30% was greater than 75%. Trial enrollment and conduct was significantly impacted by the COVID pandemic, including shortage of HCQ and inability of enrolled patients to travel. To address this, we amended the protocol to allow study Arms C and D to be combined for feasibility assessment, given that the investigational treatment was the same in the two arms, enabling enrollment to be halted when the sample size needed for feasibility assessment was complete for all study treatments. Toxicity was assessed using CTCAE v4.0. | 3 years |
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Inclusion Criteria:
ASCO/CAP guidelines, meeting one of the following:
Exclusion criteria
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| Name | Affiliation | Role |
|---|---|---|
| Angela DeMichele, MD | Abramson Cancer Center at Penn Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40897974 | Derived | DeMichele A, Clark AS, Shea E, Bayne LJ, Sterner CJ, Rohn K, Dwyer S, Pan TC, Nivar I, Chen Y, Wileyto P, Berry LR, Deluca S, Savage J, Makhlin I, Pant DK, Martin H, Egunsola A, Mears N, Goodspeed BL, Chislock EM, Graves J, Wang J, Shih N, Belka GK, Berry D, Nayak A, Feldman M, Chodosh LA. Targeting dormant tumor cells to prevent recurrent breast cancer: a randomized phase 2 trial. Nat Med. 2025 Oct;31(10):3464-3474. doi: 10.1038/s41591-025-03877-3. Epub 2025 Sep 2. |
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The target accrual was originally 60; but due to slow enrollment caused by the Covid-19 pandemic, the target enrollment was modified and study enrollment was completed after each 15 patients became evaluable in each treatment group (Arm A, Arm B, and Arm C+D combined). We hit this target after a total of 51 patients were enrolled and treated. 53 patients were randomized but two dropped out before receiving an intervention.
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| ID | Title | Description |
|---|---|---|
| FG000 | HCQ Alone (Arm A) | Hydroxychloroquine: Hydroxychloroquine |
| FG001 | EVE Alone (Arm B) | Everolimus: Everolimus |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 17, 2019 | Sep 19, 2024 |
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| Everolimus | Drug | Everolimus |
|
| FG002 |
| Combination HCQ and EVE (Arm C) |
Hydroxychloroquine: Hydroxychloroquine Everolimus: Everolimus |
| FG003 | Combination HCQ and EVE 3-mo Delay (Arm D) | Hydroxychloroquine: Hydroxychloroquine Everolimus: Everolimus |
| COMPLETED |
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| NOT COMPLETED |
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The rationale for combining Arms C+D for certain analyses is because these arms are the same intervention- Arm D was just delayed. These arms are consistent with the protocol and randomization engine.
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| ID | Title | Description |
|---|---|---|
| BG000 | HCQ Alone (Arm A) | Hydroxychloroquine: Hydroxychloroquine |
| BG001 | EVE Alone (Arm B) | Everolimus: Everolimus |
| BG002 | Combination HCQ and EVE (Arm C+D) | Hydroxychloroquine: Hydroxychloroquine Everolimus: Everolimus |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Menopausal Status | Count of Participants | Participants |
| ||||||||||||||||
| Treatment | Count of Participants | Participants |
| ||||||||||||||||
| Receptor Subtype | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Feasibility: Number of Participants Who Completed 6 Cycles of Protocol Treatment Without Grade 3 or 4 Toxicity | For the primary endpoint of feasibility, we employed ongoing Bayesian toxicity monitoring after every 3 participants completed cycle 6, assuming a Beta (1,2) prior, equivalent to one DLT observed in 3 treated participants. Early termination of a treatment arm for toxicity (non-feasibility) would occur if the posterior probability that the toxicity rate exceeds the target maximum of 30% was greater than 75%. Trial enrollment and conduct was significantly impacted by the COVID pandemic, including shortage of HCQ and inability of enrolled patients to travel. To address this, we amended the protocol to allow study Arms C and D to be combined for feasibility assessment, given that the investigational treatment was the same in the two arms, enabling enrollment to be halted when the sample size needed for feasibility assessment was complete for all study treatments. Toxicity was assessed using CTCAE v4.0. | Fifty-one of 53 participants were evaluable for the primary endpoint (excluding the 2 patients randomized to Arm D who withdrew during observation). | Posted | Count of Participants | Participants | 3 years |
|
|
|
Patients were assessed for adverse events (AE) on Day 1 of each cycle. Follow-up continued every 6 months for 3 years from the completion of study therapy, including remote follow-up during COVID and for patients at a geographical distance from the study center. On Day 1 and D15 of first two cycles, then Day 1 of remaining cycles, and up to 30 days from completion of treatment.
The rationale for combining Arms C+D for certain analyses is because these arms are the same intervention- Arm D was just delayed. These arms are consistent with the protocol and randomization engine.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | HCQ Alone (Arm A) | Hydroxychloroquine: Hydroxychloroquine | 0 | 15 | 1 | 15 | 15 | 15 |
| EG001 | EVE Alone (Arm B) | Everolimus: Everolimus | 0 | 15 | 0 | 15 | 15 | 15 |
| EG002 | Combination HCQ and EVE (Arm C+D) | Hydroxychloroquine: Hydroxychloroquine Everolimus: Everolimus | 0 | 21 | 2 | 21 | 21 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lung infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Cellulitis of arm | Infections and infestations | Systematic Assessment |
| ||
| Parainfluenzae virus infection | Infections and infestations | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Discomfort | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Liver function abnormalities (transaminitis) | Gastrointestinal disorders | Systematic Assessment |
| ||
| Mucositis/oral pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Anorexia/Weight loss | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Neutrophil count decreased | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Leukocyte count decreased | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Platelet count decreased | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Visual changes | Nervous system disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Muscle weakness, limb | Nervous system disorders | Systematic Assessment |
| ||
| CPK increased | Nervous system disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Electrolyte abnormalities | Renal and urinary disorders | Systematic Assessment | Laboratory Abnormalities |
| |
| Hyperglycemia | Endocrine disorders | Systematic Assessment | Laboratory Abnormalities |
| |
| Elevated lipids | Cardiac disorders | Systematic Assessment | Laboratory Abnormalities |
| |
| Elevated creatinine | Renal and urinary disorders | Systematic Assessment | Laboratory Abnormalities |
| |
| Fatigue | General disorders | Systematic Assessment |
| ||
| SkinRash/Discomfort | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
The results are limited by the small study sample size, low event rates, and lack of a placebo control.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Angela DeMichele | University of Pennsylvania | 2156624000 | angela.demichele@pennmedicine.upenn.edu |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 8, 2023 | Oct 31, 2024 | SAP_003.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 25, 2022 | Sep 19, 2024 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D006886 | Hydroxychloroquine |
| D000068338 | Everolimus |
| ID | Term |
|---|---|
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D020123 | Sirolimus |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Postmenopausal |
|
| Neoadjuvant Chemotherapy |
|
| No Chemotherapy |
|
| ER+/Her2+ |
|
| TNBC |
|
| ER-/Her2+ |
|