RECRUITING

Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer

Conditions

Breast Cancer tumor dormancy disseminated tumor cells DTC minimal residual disease breast cancer recurrence CDK4/6 inhibitor immune checkpoint inhibitor immunotherapy autophagy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase II Trial of Avelumab or Hydroxychloroquine With or Without Palbociclib to Eliminate Dormant Breast Cancer (PALAVY)

Quick Facts

Study Start:2021-06-01

Study Completion:2028-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04841148

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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	* 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: * 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.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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

* 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:
* 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.

Contacts and Locations

Study Contact

Lauren Bayne, PhD

CONTACT

215-615-2367

breastcancerclinicaltrials@pennmedicine.upenn.edu

Pauleen Sanchez, BA

CONTACT

215-615-2367

breastcancerclinicaltrials@pennmedicine.upenn.edu

Principal Investigator

Angela DeMichele, MD

PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Study Locations (Sites)

Georgetown University

Washington, District of Columbia, 20007

United States

University of Chicago

Chicago, Illinois, 60637

United States

Indiana University

Indianapolis, Indiana, 46202

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Vanderbilt University

Nashville, Tennessee, 37232

United States

University of Washington

Seattle, Washington, 98195

United States

Collaborators and Investigators

Sponsor: Abramson Cancer Center at Penn Medicine

Angela DeMichele, MD, PRINCIPAL_INVESTIGATOR, University of Pennsylvania

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-06-01

Study Completion Date2028-05

Study Record Updates

Study Start Date2021-06-01

Study Completion Date2028-05

Terms related to this study

Keywords Provided by Researchers

tumor dormancy
disseminated tumor cells
DTC
minimal residual disease
breast cancer recurrence
CDK4/6 inhibitor
immune checkpoint inhibitor
immunotherapy
autophagy

Additional Relevant MeSH Terms

Breast Cancer