Breast CancerPhase 2PALAVYNCT04841148
Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer
A Phase 2 study testing HCQ, Avelumab and Palbociclib in people with Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- HCQ, Avelumab and Palbociclib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 7 sitesUnited States
- Study dates
- 1 Jun 2021to May 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Bone marrow aspirate after completion of all definitive therapy demonstrates detectable DTCs (via IHC) as performed by central laboratory assessment at University of Pennsylvania.
- History of stage II-III histologically-confirmed ER+/Her2 neg invasive breast cancer with no evidence of recurrent local or distant disease (by American Joint Committee on Cancer 7th edition). Patients with bilateral breast cancer are eligible, so long as both cancers are ER+/Her2 neg, at least one meets other eligibility criteria and patient is treated with curative intent. For patients who undergo neoadjuvant therapy, eligibility is based upon pathologic stage of residual disease at surgery.
- ER+/Her2 neg receptor status on breast primary tumor (by American Society of Clinical Oncology/College of American Pathologists guidelines). Any partial response (PR) status is allowed. Tumors that are ER negative and PR positive are not eligible. Patients who undergo neoadjuvant therapy are eligible if either the pre-treatment biopsy or residual disease at surgery is ER+/Her2 neg.
- Patients must have completed all primary and adjuvant therapy (including surgery, chemotherapy, and radiation) with the exception of adjuvant endocrine therapy. Prior treatment-related toxicity must be resolved to ≤ Grade 1 with the exception of alopecia and peripheral neuropathy, prior to study enrollment.
- Patients may have received prior CDK4/6 inhibitor therapy with an agent other than Palbociclib. Patients must have discontinued CDK4/6 inhibitor at least 6 months prior to screening.
- Patients must be receiving adjuvant endocrine therapy at the time of enrollment. Patients are eligible to enroll within 2-7 years after initiation of adjuvant endocrine therapy. Use of tamoxifen as adjuvant endocrine therapy during study treatment is not allowed on hydroxychloroquine arms due to the potential drug-drug interaction with hydroxychloroquine. However, patients on tamoxifen at the time of screening may enroll on the treatment trial if switched to an aromatase inhibitor at least 21 days prior to starting study therapy in the event patient is randomized to a hydroxychloroquine containing arm. Premenopausal patients on concurrent ovarian suppression are eligible. Patients on any other adjuvant endocrine therapy, including any investigational therapy, are ineligible.
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- Patients receiving bone modifying agents (bisphosphonates or rank-ligand inhibitors) at the time of screening may continue this therapy. Bone modifying agents may not be initiated while receiving study treatment.
- No concurrent enrollment on another investigational therapy clinical trial.
- Men and women, age ≥ 18 years.
- No contraindications to the study medications (refer to Section 7.2) or uncontrolled medical illness.
- Adequate bone marrow, liver, and renal function and other parameters.
- Ability to speak and understand English
Who cannot join
- Patients with a history of another prior invasive breast cancer are ineligible. Patients with prior Ductal carcinoma in situ (DCIS) of the breast are eligible if this was diagnosed > 5 years prior to enrollment. Patients with prior invasive malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment.
- 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.
- EKG demonstrating QT interval corrected (QTC) > 480 ms
- Any severe and/or uncontrolled medical conditions or other conditions that could affect subject participation in the study including:
- Chronic autoimmune disease
- History or evidence of increased cardiovascular risk including any of the following:
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- Current clinical significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation
- History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to enrollment
- Current ≥ Class II congestive heart failure as defined by New York Heart Association
- History of pneumonitis/interstitial lung disease or severely impaired lung function with a previously documented spirometry and Diffusing Capacity of Lung for Carbon Monoxide (DLCO) that is 50% of the normal predicted value (these tests not required at screening; prior results, if performed for standard of care should be referenced) and/or O2 saturation that is 88% or less at rest on room air
- Uncontrolled diabetes
- Active (acute or chronic) or uncontrolled severe infections
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
- HIV positive patient who are receiving combination anti-retroviral therapy are ineligible because of the potential for pharmacokinetic interactions or increased immunosuppression with Palbociclib. However, HIV per se is not a contraindication to study participation and HIV testing is not required.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of hydroxychloroquine (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis. Patients receiving therapeutic anticoagulation are not eligible for study participation.
- History of retinopathy or retinal vein occlusion
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago
Chicago, Illinois, 60637
Indiana University
Indianapolis, Indiana, 46202
Vanderbilt University
Nashville, Tennessee, 37232
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Washington
Seattle, Washington, 98195
Georgetown University
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase II Trial of Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer (PALAVY)
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.
Read the 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
- Being tested
- HCQ, Avelumab, Palbociclib
- Keywords
- tumor dormancy, disseminated tumor cells, DTC, minimal residual disease, breast cancer recurrence, CDK4/6 inhibitor, immune checkpoint inhibitor, immunotherapy, autophagy
- Medical subject headings
- Breast Neoplasms, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HCQDrug
Also called Hydroxychloroquine sulfate, Plaquenil
600 mg tablets twice daily D1-28 of each 28-day cycle
AvelumabDrug
Also called MSB0010718C, Bavencio
10 mg/kg, IV, D1 and D15 of each 28-day cycle
PalbociclibDrug
Also called Ibrance
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.
| Study group | Role | What they receive |
|---|---|---|
| HCQ | Experimental | Patients will receive HCQ, 600 mg twice daily D1-28 of each 28-day cycle. Receives: Drug: HCQ |
| Avelumab | Experimental | Patients will receive Avelumab, 10 mg/kg, IV, D1 and D15 of each 28-day cycle. Receives: Drug: Avelumab |
| Palbociclib and Avelumab | Experimental | Patients will receive Palbociclib 125 mg daily, by mouth on D1-21 concurrently with Avelumab, 10 mg/kg IV on D1 and D15 of each 28-day cycle Receives: Drug: Avelumab; Drug: Palbociclib |
| Palbociclib and HCQ | Experimental | Patients will receive Palbociclib 75 mg daily, by mouth on D1-28 concurrently with HCQ, 600 mg twice daily D1-28 of each 28-day cycle. Receives: Drug: HCQ; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the efficacy of HCQ or Avelumab, alone or in combination with Palbociclib, in eradicating DTCs
Endpoint: Proportion of subjects in each treatment arm with clearance of DTCs at the end of 6 cycles of therapy.
Measured: Efficacy is assessed at the end of Cycle 6 (each cycle is 28 days).
Secondary outcomes (2)
Determine the safety and tolerability of HCQ or Avelumab, alone or in combination with Palbociclib, in this Phase II study: adverse events
Endpoint: Occurrence of an adverse event on treatment by NCI CTCAE v5 criteria.
Measured: Toxicity is assessed from the first dose of study treatment through 30 days after the last dose of study treatment
Estimate the risk of recurrence after treatment with Palbociclib, Avelumab and HCQ, alone or in combination
Endpoint: 3-year recurrence free survival (RFS)
Measured: Recurrence free survival (RFS) will be assessed 3 years after the completion of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start1 Jun 2021
- Primary completionJul 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, Translational Breast Cancer Research Consortium, Pfizer, Breast Cancer Research Foundation
- Responsible party
- Sponsor
- Investigators
- Angela DeMichele, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04841148
- Sponsor's protocol ID
- UPCC 01121
- Other IDs
- IRB# 848471, TBCRC 046
- Acronym
- PALAVY
- Status last verified
- Oct 2026
- First submitted
- 6 Apr 2021
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer (PALAVY)
- ClinicalTrials.gov ID
- NCT04841148
- Acronym / sponsor ID
- PALAVY / UPCC 01121
- Conditions
- Breast Cancer
- Keywords
- tumor dormancy, disseminated tumor cells, DTC, minimal residual disease, breast cancer recurrence, CDK4/6 inhibitor, immune checkpoint inhibitor, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Johns Hopkins University, Translational Breast Cancer Research Consortium, Pfizer, Breast Cancer Research Foundation
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- Jul 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 12 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HCQ | Experimental | Drug: HCQPatients will receive HCQ, 600 mg twice daily D1-28 of each 28-day cycle. |
| Avelumab | Experimental | Drug: AvelumabPatients will receive Avelumab, 10 mg/kg, IV, D1 and D15 of each 28-day cycle. |
| Palbociclib and Avelumab | Experimental | Drug: Avelumab, Drug: PalbociclibPatients will receive Palbociclib 125 mg daily, by mouth on D1-21 concurrently with Avelumab, 10 mg/kg IV on D1 and D15 of each 28-day cycle |
| Palbociclib and HCQ | Experimental | Drug: HCQ, Drug: PalbociclibPatients will receive Palbociclib 75 mg daily, by mouth on D1-28 concurrently with HCQ, 600 mg twice daily D1-28 of each 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Bone marrow aspirate after completion of all definitive therapy demonstrates detectable DTCs (via IHC) as performed by central laboratory assessment at University of Pennsylvania.
- History of stage II-III histologically-confirmed ER+/Her2 neg invasive breast cancer with no evidence of recurrent local or distant disease (by American Joint Committee on Cancer 7th edition). Patients with bilateral breast cancer are eligible, so long as both cancers are ER+/Her2 neg, at least one meets other eligibility criteria and patient is treated with curative intent. For patients who undergo neoadjuvant therapy, eligibility is based upon pathologic stage of residual disease at surgery.
- ER+/Her2 neg receptor status on breast primary tumor (by American Society of Clinical Oncology/College of American Pathologists guidelines). Any partial response (PR) status is allowed. Tumors that are ER negative and PR positive are not eligible. Patients who undergo neoadjuvant therapy are eligible if either the pre-treatment biopsy or residual disease at surgery is ER+/Her2 neg.
- Patients must have completed all primary and adjuvant therapy (including surgery, chemotherapy, and radiation) with the exception of adjuvant endocrine therapy. Prior treatment-related toxicity must be resolved to ≤ Grade 1 with the exception of alopecia and peripheral neuropathy, prior to study enrollment.
- Patients may have received prior CDK4/6 inhibitor therapy with an agent other than Palbociclib. Patients must have discontinued CDK4/6 inhibitor at least 6 months prior to screening.
Key exclusion criteria (18 listed)
- Patients with a history of another prior invasive breast cancer are ineligible. Patients with prior Ductal carcinoma in situ (DCIS) of the breast are eligible if this was diagnosed > 5 years prior to enrollment. Patients with prior invasive malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment.
- 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.
- EKG demonstrating QT interval corrected (QTC) > 480 ms
- Any severe and/or uncontrolled medical conditions or other conditions that could affect subject participation in the study including:
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HCQAlso: Hydroxychloroquine sulfate, Plaquenil600 mg tablets twice daily D1-28 of each 28-day cycle | Drug | HCQ, Palbociclib and HCQ |
| AvelumabAlso: MSB0010718C, Bavencio10 mg/kg, IV, D1 and D15 of each 28-day cycle | Drug | Avelumab, Palbociclib and Avelumab |
| PalbociclibAlso: Ibrance125 mg capsule daily, by mouth on D1-21 concurrently with Avelumab. Or 75 mg capsule daily, by mouth on D1-28 concurrently with HCQ. | Drug | Palbociclib and Avelumab, Palbociclib and HCQ |
Primary outcome
Determine the efficacy of HCQ or Avelumab, alone or in combination with Palbociclib, in eradicating DTCs
Time frame: Efficacy is assessed at the end of Cycle 6 (each cycle is 28 days).
Endpoint: Proportion of subjects in each treatment arm with clearance of DTCs at the end of 6 cycles of therapy.
2 secondary outcomes
Determine the safety and tolerability of HCQ or Avelumab, alone or in combination with Palbociclib, in this Phase II study: adverse events
Time frame: Toxicity is assessed from the first dose of study treatment through 30 days after the last dose of study treatment
Estimate the risk of recurrence after treatment with Palbociclib, Avelumab and HCQ, alone or in combination
Time frame: Recurrence free survival (RFS) will be assessed 3 years after the completion of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela DeMichele, MD principal investigator
University of Pennsylvania
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HCQ, Avelumab and Palbociclib in people with Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the efficacy of HCQ or Avelumab, alone or in combination with Palbociclib, in eradicating DTCs (time frame: Efficacy is assessed at the end of Cycle 6 (each cycle is 28 days).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.