Ritonavir and Its Effects on Biomarkers in Women Undergoing Surgery for Newly Diagnosed Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Procedure: therapeutic conventional surgery
- Registration Number
- NCT01009437
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- Brief Summary
RATIONALE: Ritonavir may stop the growth of tumor cells by blocking some of the enzymes needed for cancer cell growth. Studying samples of blood and tissue from patients with breast cancer in the laboratory may help doctors learn more about the effects of ritonavir on biomarkers involved in breast cancer growth.
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
OBJECTIVES:
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ritonavir - Maximum Tolerated Dose (II) therapeutic conventional surgery 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. Control Arm - No Ritonavir therapeutic conventional surgery 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. Ritonavir - Escalating Doses (I) ritonavir 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 - Escalating Doses (I) therapeutic conventional surgery 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 - Maximum Tolerated Dose (II) ritonavir 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.
- Primary Outcome Measures
Name Time Method Inhibition of breast cancer by targeting Hsp90-Akt pathway Pre and Post Treatment
- Secondary Outcome Measures
Name Time Method Alteration of plasma levels of eicosanoids Pre Treatment and 3 Hours Post Treatment Induction of Hsp70 in peripheral blood mononuclear cells Pre Treatment and 3 Hours Post Treatment Reduction of ERα in ERα+ tumors Pre and Post Treatment Activation of apoptosis markers Pre and Post Treatment Modulation of autophagy markers Pre and Post Treatment Changes in TNF-α and IL-6 levels as well as reduction in intratumoral nuclear NF-kB and phospho-Stat3 Pre and Post Treatment Alteration of urine eicosanoid levels Pre and Post Treatment Alteration of plasma and urine eicosanoid levels resulting from tumor resection. Pre and Post Treatment Induction of the unfolded protein response (UPR) assayed by grp78 or related markers (phospho-PERK, ATF-4, and CHOP) pre- and post-surgery inhibition of tumor growth markers (Ki67 LI, Hsp90, phosphorylated AKT) pre- and post-surgery
Trial Locations
- Locations (2)
Masonic Cancer Center, University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
The Kimmel Cancer Center at Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States