PENN-Surveillance Markers of Utility for Recurrence After (Neo)Adjuvant Therapy for Breast Cancer
Primary Purpose
Breast Cancer
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Research Blood Collection
Sponsored by
About this trial
This is an interventional screening trial for Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically-confirmed primary invasive breast cancer within 5 years of study entry
Qualifying risk status, at diagnosis utilizing receptor testing by ASCO/CAP guidelines, meeting at least one of the following:
- Pathologically-confirmed invasive breast cancer in axillary lymph nodes, regardless of receptors
- Primary tumor with triple negative subtype: estrogen receptor (ER) < 10%, progesterone receptor (PR) < 10% and negative Her2-overexpression by ASCO-CAP guidelines
- Primary tumor that is ER+/Her2 negative/Lymph node negative with a Breast Cancer Recurrence Score of ≥ 25 per the Genomic Health Oncotype DX breast cancer test and/or HighRisk MammaPrint
- Evidence of residual disease in the breast on pathologic assessment after neoadjuvant chemotherapy
- Completed all primary therapy (surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy at least 4 weeks prior to study entry. Concurrent receipt of adjuvant endocrine therapy and bone modifying agents is allowed per standard of care. However, tamoxifen is not allowed on recurrence prevention trials that use Hydroxychloroquine. Patients on tamoxifen may still be enrolled on Penn-Surmount as long as the treating physician is aware and tamoxifen can be stopped if patient is DTC positive.
- No evidence of local or distant recurrent disease by physical examination, blood tests (CBC, LFTs, Alk Phos), or symptom-directed imaging, per NCCN guidelines.
- Adequate bone marrow function as shown by: ANC >/= 1.5x10^9/L, Platelets >/= 100x10^9/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
- Normal coagulation studies: PT and PTT ≤ 1.5 x upper limit of normal per institutional laboratory range
- Anti-coagulation 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 enrollment. 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 </= 1.5 x ULN
- Willing to undergo bone marrow aspiration and blood specimen collection per protocol specifications
- Age 18 or over and able to give informed consent
Exclusion Criteria:
- Concurrent enrollment on another investigational therapy
- 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 QTC > 480 ms
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- History or evidence of increased cardiovascular risk including any of the following: (i) current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation, (ii) History of acute coronary syndromes (including myocardial infarction and unstable angina, coronary angioplasty, or stenting within 6 months prior to enrollment, (iii) 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 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
- 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
- History of major surgical resection involving the stomach or small bowel, or pre-existing impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, Crohn's disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis
- History of retinopathy or retinal vein occlusion
- Female patients who are pregnant or breast feeding. Women of childbearing potential must have a negative urine or serum pregnancy test.
- Patients who have received prior treatment with a CDK4/6 inhibitor
- Patients with a known hypersensitivity to Hydroxychloroquine or any of its derivatives
- Patients with prior hydroxychloroquine exposure for a duration of > 1 month since the completion of the patient's primary therapy (definitive surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy
- Patients who have initiated bone modifying agents within 3 months prior to study enrollment
- 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.
Sites / Locations
- Abramson Cancer Center of the University of PennsylvaniaRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Screening Bone Marrow Aspirate
Arm Description
All patients will undergo screening bone marrow aspirate to test for disseminated tumor cells (DTCs) by immunohistochemistry. The bone marrow sample is also used for other research tests.
Outcomes
Primary Outcome Measures
Incidence and frequency of disseminated tumor cells
Bone marrow sample is evaluated for DTCs by a standard immunohistochemistry assay (DTC-IHC)
Secondary Outcome Measures
Full Information
NCT ID
NCT02732171
First Posted
April 4, 2016
Last Updated
October 11, 2023
Sponsor
Abramson Cancer Center at Penn Medicine
1. Study Identification
Unique Protocol Identification Number
NCT02732171
Brief Title
PENN-Surveillance Markers of Utility for Recurrence After (Neo)Adjuvant Therapy for Breast Cancer
Official Title
PENN-Surveillance Markers of Utility for Recurrence After (Neo)Adjuvant Therapy for Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2016 (undefined)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single center, prospective cross-sectional study of women who have completed therapy for primary breast cancer within 5 years of diagnosis and are at increased risk for relapse.
Patients will undergo screening bone marrow aspirate to test for presence of disseminated tumor cells (DTCs) Patients who harbor DTCs will be offered the opportunity for enrollment into a clinical trial of therapy targeting DTCs to prevent recurrence (separate protocols).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
7. Study Design
Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
600 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Screening Bone Marrow Aspirate
Arm Type
Other
Arm Description
All patients will undergo screening bone marrow aspirate to test for disseminated tumor cells (DTCs) by immunohistochemistry. The bone marrow sample is also used for other research tests.
Intervention Type
Other
Intervention Name(s)
Research Blood Collection
Intervention Description
Multiple tubes of research blood collected for biomarker analyses (circulating tumor material, immune profiling)
Primary Outcome Measure Information:
Title
Incidence and frequency of disseminated tumor cells
Description
Bone marrow sample is evaluated for DTCs by a standard immunohistochemistry assay (DTC-IHC)
Time Frame
DTCs will be assessed annually up to 5 years from date of primary diagnosis
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically-confirmed primary invasive breast cancer within 5 years of study entry
Qualifying risk status, at diagnosis utilizing receptor testing by ASCO/CAP guidelines, meeting at least one of the following:
Pathologically-confirmed invasive breast cancer in axillary lymph nodes, regardless of receptors
Primary tumor with triple negative subtype: estrogen receptor (ER) < 10%, progesterone receptor (PR) < 10% and negative Her2-overexpression by ASCO-CAP guidelines
Primary tumor that is ER+/Her2 negative/Lymph node negative with a Breast Cancer Recurrence Score of ≥ 25 per the Genomic Health Oncotype DX breast cancer test and/or HighRisk MammaPrint
Evidence of residual disease in the breast on pathologic assessment after neoadjuvant chemotherapy
Completed all primary therapy (surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy at least 4 weeks prior to study entry. Concurrent receipt of adjuvant endocrine therapy and bone modifying agents is allowed per standard of care. However, tamoxifen is not allowed on recurrence prevention trials that use Hydroxychloroquine. Patients on tamoxifen may still be enrolled on Penn-Surmount as long as the treating physician is aware and tamoxifen can be stopped if patient is DTC positive.
No evidence of local or distant recurrent disease by physical examination, blood tests (CBC, LFTs, Alk Phos), or symptom-directed imaging, per NCCN guidelines.
Adequate bone marrow function as shown by: ANC >/= 1.5x10^9/L, Platelets >/= 100x10^9/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
Normal coagulation studies: PT and PTT ≤ 1.5 x upper limit of normal per institutional laboratory range
Anti-coagulation 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 enrollment. 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 </= 1.5 x ULN
Willing to undergo bone marrow aspiration and blood specimen collection per protocol specifications
Age 18 or over and able to give informed consent
Exclusion Criteria:
Concurrent enrollment on another investigational therapy
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 QTC > 480 ms
Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
History or evidence of increased cardiovascular risk including any of the following: (i) current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation, (ii) History of acute coronary syndromes (including myocardial infarction and unstable angina, coronary angioplasty, or stenting within 6 months prior to enrollment, (iii) 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 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
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
History of major surgical resection involving the stomach or small bowel, or pre-existing impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, Crohn's disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
Patients with an active, bleeding diathesis
History of retinopathy or retinal vein occlusion
Female patients who are pregnant or breast feeding. Women of childbearing potential must have a negative urine or serum pregnancy test.
Patients who have received prior treatment with a CDK4/6 inhibitor
Patients with a known hypersensitivity to Hydroxychloroquine or any of its derivatives
Patients with prior hydroxychloroquine exposure for a duration of > 1 month since the completion of the patient's primary therapy (definitive surgery, (neo)adjuvant chemotherapy, adjuvant radiation, and/or Her2-directed therapy) for the index malignancy
Patients who have initiated bone modifying agents within 3 months prior to study enrollment
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Angela DeMichele, MD
Phone
855-216-0098
Email
PennCancerTrials@emergingmed.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela DeMichele, MD
Organizational Affiliation
Abramson Cancer Center at Penn Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abramson Cancer Center of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angela DeMichele, MD
Phone
855-216-0098
Email
PennCancerTrials@emergingmed.com
12. IPD Sharing Statement
Learn more about this trial
PENN-Surveillance Markers of Utility for Recurrence After (Neo)Adjuvant Therapy for Breast Cancer
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