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AzTrials

Breast CancerPhase 1NCT01009437

Ritonavir and Its Effects on Biomarkers in Women Undergoing Surgery for Newly Diagnosed Breast Cancer

A Phase 1 study testing ritonavir and therapeutic conventional surgery in people with Breast Cancer, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
ritonavir and therapeutic conventional surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
2 sitesUnited States
Study dates
26 May 2010to Jul 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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+
Show all 18Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Masonic Cancer Center, University of Minnesota

    Minneapolis, Minnesota, 55455

  • The Kimmel Cancer Center at Jefferson University

    Philadelphia, Pennsylvania, 19107

Other trials in United States

About this study

Official title: A Phase I/II Trial of Short Course Pre-Operative Ritonavir To Determine Akt Inhibition in Breast Cancer

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.

Read the 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.

Conditions
Breast Cancer
Keywords
HER2-negative breast cancer, HER2-positive breast cancer, estrogen receptor-positive breast cancer, triple-negative breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, ductal breast carcinoma in situ
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ritonavirDrug

    Also called NORVIR® tablets

    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 surgeryProcedure or surgery

    Also called Surgery

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

Study groups in NCT01009437
Study groupRoleWhat they receive
Control Arm - No RitonavirActive comparatorFive 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.
Receives: Procedure: therapeutic conventional surgery
Ritonavir - Escalating Doses (I)ExperimentalStandard 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-
Receives: Drug: ritonavir; Procedure: therapeutic conventional surgery
Ritonavir - Maximum Tolerated Dose (II)ExperimentalPhase 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.
Receives: Drug: ritonavir; Procedure: therapeutic conventional surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Inhibition of breast cancer by targeting Hsp90-Akt pathway

    Measured: Pre and Post Treatment

Secondary outcomes (10)

  1. Activation of apoptosis markers

    Measured: Pre and Post Treatment

  2. Modulation of autophagy markers

    Measured: Pre and Post Treatment

  3. Alteration of plasma levels of eicosanoids

    Measured: Pre Treatment and 3 Hours Post Treatment

  4. Induction of Hsp70 in peripheral blood mononuclear cells

    Measured: Pre Treatment and 3 Hours Post Treatment

  5. Reduction of ERα in ERα+ tumors

    Measured: Pre and Post Treatment

  6. Changes in TNF-α and IL-6 levels as well as reduction in intratumoral nuclear NF-kB and phospho-Stat3

    Measured: Pre and Post Treatment

  7. Alteration of urine eicosanoid levels

    Measured: Pre and Post Treatment

  8. Alteration of plasma and urine eicosanoid levels resulting from tumor resection.

    Measured: Pre and Post Treatment

  9. Induction of the unfolded protein response (UPR) assayed by grp78 or related markers (phospho-PERK, ATF-4, and CHOP)

    Measured: pre- and post-surgery

  10. inhibition of tumor growth markers (Ki67 LI, Hsp90, phosphorylated AKT)

    Measured: pre- and post-surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2009 (estimated)
  2. Study start26 May 2010
  3. Primary completionJul 2014
  4. Study completionJul 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01009437
Sponsor's protocol ID
2008NTLS083
Other IDs
UMN-0809M45461
Status last verified
Dec 2017
First submitted
5 Nov 2009
Last updated
5 Dec 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ritonavir and therapeutic conventional surgery in people with Breast Cancer, run by Masonic Cancer Center, University of Minnesota at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Inhibition of breast cancer by targeting Hsp90-Akt pathway (time frame: Pre and Post Treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01009437.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2017.

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