NCT01009437

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
28

participants targeted

Target at P25-P50 for phase_1 breast-cancer

Timeline
Completed

Started May 2010

Typical duration for phase_1 breast-cancer

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 6, 2009

Completed
7 months until next milestone

Study Start

First participant enrolled

May 26, 2010

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2014

Completed
Last Updated

December 5, 2017

Status Verified

December 1, 2017

Enrollment Period

4.1 years

First QC Date

November 5, 2009

Last Update Submit

December 3, 2017

Conditions

Breast Cancer

Keywords

HER2-negative breast cancerHER2-positive breast cancerestrogen receptor-positive breast cancertriple-negative breast cancerstage I breast cancerstage II breast cancerstage IIIA breast cancerstage IIIB breast cancerstage IIIC breast cancerstage IV breast cancerductal breast carcinoma in situ

Outcome Measures

Primary Outcomes (1)

  • Inhibition of breast cancer by targeting Hsp90-Akt pathway

    Pre and Post Treatment

Secondary Outcomes (10)

  • Activation of apoptosis markers

    Pre and Post Treatment

  • Modulation of autophagy markers

    Pre and Post Treatment

  • 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

  • +5 more secondary outcomes

Study Arms (3)

Control Arm - No Ritonavir

ACTIVE COMPARATOR

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.

Procedure: therapeutic conventional surgery

Ritonavir - Escalating Doses (I)

EXPERIMENTAL

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-

Drug: ritonavirProcedure: therapeutic conventional surgery

Ritonavir - Maximum Tolerated Dose (II)

EXPERIMENTAL

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.

Drug: ritonavirProcedure: therapeutic conventional surgery

Interventions

ritonavirDRUG

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.

Also known as: NORVIR® tablets
Ritonavir - Escalating Doses (I)Ritonavir - Maximum Tolerated Dose (II)
therapeutic conventional surgeryPROCEDURE

Tissue collection is from all patients, including the control, phase I and phase II patients.

Also known as: Surgery
Control Arm - No RitonavirRitonavir - Escalating Doses (I)Ritonavir - Maximum Tolerated Dose (II)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Newly diagnosed biopsy proven breast cancer for which a lumpectomy or mastectomy is planned.
  • 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
  • +3 more criteria

You may not qualify if:

  • Pregnant or lactating.
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Kimmel Cancer Center at Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Breast NeoplasmsTriple Negative Breast NeoplasmsCarcinoma, Intraductal, Noninfiltrating

Interventions

RitonavirSurgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeBreast Carcinoma In SituCarcinoma in SituNeoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • David A. Potter, M.D., Ph.D.

    Masonic Cancer Center, University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2009

First Posted

November 6, 2009

Study Start

May 26, 2010

Primary Completion

July 1, 2014

Study Completion

July 1, 2014

Last Updated

December 5, 2017

Record last verified: 2017-12

Locations

US(2)