Ritonavir and Its Effects on Biomarkers in Women Undergoing Surgery for Newly Diagnosed Breast Cancer
NCT ID: NCT01009437
Last Updated: 2017-12-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
28 participants
INTERVENTIONAL
2010-05-26
2014-07-31
Brief Summary
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PURPOSE: This phase I/II trial is studying the best dose of ritonavir and its effects on biomarkers in women undergoing surgery for newly diagnosed breast cancer.
Detailed Description
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* Determine the effects of ritonavir on Akt activity, UPR, Ki67 LI, and ROS in a triple-negative breast cancer model.
* Determine the maximum tolerated dose of ritonavir in women with newly diagnosed breast cancer. (Phase I - enrollment complete)
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study. \*Note: This trial never moved forward to Phase ll.
Control Group - Five patients with estrogen receptor positive (ER+) and human epidermal growth factor 2 negative (HER2-) breast cancer are enrolled before the start of phase I recruitment.
Phase I Group - Twelve breast cancer patients with either 1)ER+, HER2-, or 2)ER+, HER2+, or 3) ER-, HER2+, or 4) ER-, PR+, HER2-, or 5) ER-, PR-, HER2- will be enrolled for dose escalation study.
Phase II Group - Nineteen ER+, HER2- patients will be enrolled for ritonavir pharmacokinetic study after maximum tolerated dose (MTD) is established.
* Control: Patients do not receive ritonavir.
* Phases I and II: Patients receive oral ritonavir twice daily for 5 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery as deemed appropriate by the surgeon and based on patient preference (mastectomy or lumpectomy with sentinel node procedure and/or axillary node dissection).
All patients undergo blood and tissue sample collection periodically for biomarker research studies. Samples from patients enrolled in the control group are compared with the samples from patients enrolled in phase I and II.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
DIAGNOSTIC
NONE
Study Groups
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Control Arm - No Ritonavir
Five ER+, HER2- breast cancer patients meeting all study eligibility will be enrolled prior to the start of phase I recruitment to act as controls (no ritonavir will be given-will receive therapeutic conventional surgery) to confirm that anesthesia does not affect EET levels. Core biopsies, surgical tumor/normal tissue and pre- and post- surgery blood samples will be collected for comparison with the treatment group.
therapeutic conventional surgery
Tissue collection is from all patients, including the control, phase I and phase II patients.
Ritonavir - Escalating Doses (I)
Standard phase I dose escalation (with therapeutic conventional surgery) will be used with 3 levels of ritonavir given - 200 mg bid, 400 mg bid, and 600 mg bid for the following groups:
1. ER+, HER2-
2. ER+, HER2+
3. ER-, HER2+
4. ER-, PR+, HER2-
5. ER-, PR-, HER2-
ritonavir
Phase I: Dose escalation will be used with 3 levels of ritonavir given - 200 mg twice a day (bid), 400 mg bid, and 600 mg bid.
Phase II: Dose will be maximum tolerated dose from Phase I.
therapeutic conventional surgery
Tissue collection is from all patients, including the control, phase I and phase II patients.
Ritonavir - Maximum Tolerated Dose (II)
Phase II: Once the maximum tolerated dose (MTD) of ritonavir is established, 19 ER+, HER2- patients will be enrolled at MTD during the phase II component along with therapeutic conventional surgery.
ritonavir
Phase I: Dose escalation will be used with 3 levels of ritonavir given - 200 mg twice a day (bid), 400 mg bid, and 600 mg bid.
Phase II: Dose will be maximum tolerated dose from Phase I.
therapeutic conventional surgery
Tissue collection is from all patients, including the control, phase I and phase II patients.
Interventions
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ritonavir
Phase I: Dose escalation will be used with 3 levels of ritonavir given - 200 mg twice a day (bid), 400 mg bid, and 600 mg bid.
Phase II: Dose will be maximum tolerated dose from Phase I.
therapeutic conventional surgery
Tissue collection is from all patients, including the control, phase I and phase II patients.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Control Selection
* ER+, HER2-: estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2 -) as defined according to institutional standards.
* Phase I Selection
* ER+, HER2-
* ER+, HER2+
* ER-, HER2+
* ER-, PR+, HER2-
* ER-, PR-, HER2-
* Phase II Selection
* ER+HER2-: as defined for controls Menstrual status will be noted as either pre- or postmenopausal. For the purpose of this study, postmenopausal is defined as no menstrual period for 12 months or longer or bilateral oophorectomy
* Sufficient tumor tissue from the diagnostic core biopsy, either as a block or a minimum of 5 slides
* Tumor must be greater than 1 centimeter as measured by clinical exam, mammogram, ultrasound or MRI. - No prior treatment for breast cancer in the affected breast.
* Karnofsky performance status \>70%
* No prior treatment for breast cancer in the affected breast
* Adequate organ function for receiving study drug within 14 days 1st dose of study drug
* Women of childbearing potential are required to use an effective method of contraception
* Voluntary written consent
Exclusion Criteria
* Known positive HIV status or on medications for HIV
* Diagnosis of diabetes due to potential problems with insulin resistance and hyperglycemia
* Any pre-existing gastrointestinal complaints including nausea, abdominal pain and/or diarrhea
* Known hypersensitivity to ritonavir or any of the tablet ingredients
* Co-administration of ritonavir is contraindicated with any of the drugs - Contraindicated Drugs because competition for primarily CYP3A by ritonavir could result in inhibition of the metabolism of these drugs and create the potential for serious and/or life-threatening reactions such as cardiac arrhythmias, prolonged or increased sedation, and respiratory depression. Voriconazole is an exception in that co-administration of ritonavir and voriconazole results in a significant decrease in plasma concentrations of voriconazole. If the patient cannot discontinue a contraindicated drug, she is not eligible for the trial.
* Incompatible Drugs
18 Years
FEMALE
No
Sponsors
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Susan G. Komen Breast Cancer Foundation
OTHER
Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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David A. Potter, M.D., Ph.D.
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
The Kimmel Cancer Center at Jefferson University
Philadelphia, Pennsylvania, United States
Countries
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Other Identifiers
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UMN-0809M45461
Identifier Type: OTHER
Identifier Source: secondary_id
2008NTLS083
Identifier Type: -
Identifier Source: org_study_id