Study of the Efficacy of Chloroquine in the Treatment of Ductal Carcinoma in Situ (The PINC Trial)

This study is currently recruiting participants.
Verified March 2014 by Inova Health Care Services
Sponsor:
Collaborators:
George Mason University
U.S. Army Medical Research and Materiel Command
Information provided by (Responsible Party):
Inova Health Care Services
ClinicalTrials.gov Identifier:
NCT01023477
First received: December 1, 2009
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to test the hypothesis that chloroquine will reduce the ability of ductal carcinoma in situ (DCIS) to survive and spread. Participants will receive either chloroquine standard dose (500mg/week) or chloroquine low dose (250mg/week) for 1 month prior to surgical removal of the tumor.


Condition Intervention Phase
Carcinoma, Intraductal, Noninfiltrating
DCIS
Ductal Carcinoma In Situ
Drug: Chloroquine Standard Dose (500mg/week)
Drug: Chloroquine Low Dose (250mg/week)
Procedure: Breast Biopsy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Preventing Invasive Breast Neoplasia With Chloroquine (PINC) Trial

Resource links provided by NLM:


Further study details as provided by Inova Health Care Services:

Primary Outcome Measures:
  • Tumor response evaluated by RECIST criteria as measured by breast MRI. [ Time Frame: Immediately preceding study drug treatment and again after treatment prior to surgery. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the safety and dosing efficacy of chloroquine in the treatment of patients with DCIS. [ Time Frame: Continually ] [ Designated as safety issue: Yes ]
  • Evaluate the effect of therapy on the progenitor cell yield and invasive capacity ex vivo. [ Time Frame: At the time of breast biopsy and again at time of surgery. ] [ Designated as safety issue: No ]
  • Evaluate the effect of treatment on the proteomic and molecular cytogenetic profiles of the DCIS lesions. [ Time Frame: At the time of breast biopsy and again at the time of surgery. ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: December 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chloroquine Standard Dose (500mg/week)
Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week).
Drug: Chloroquine Standard Dose (500mg/week)
Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.
Other Name: Aralen
Procedure: Breast Biopsy
Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery.
Other Names:
  • Biopsy
  • DCIS
  • Ductal Carcinoma in Situ
Experimental: Chloroquine Low Dose (250mg/week)
Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week).
Drug: Chloroquine Low Dose (250mg/week)
Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.
Other Name: Aralen
Procedure: Breast Biopsy
Patients diagnosed with DCIS will undergo a breast biopsy prior to the start of study treatment. This biopsy is entirely voluntary and is not required to remain in the study. The biopsy will allow researchers to study the tissue for biomarkers and to determine how the DCIS tissue changes during treatment. Additional samples of the DCIS tissue will be collected at the time of surgery.
Other Names:
  • Biopsy
  • DCIS
  • Ductal Carcinoma in Situ

Detailed Description:

The purpose of this study is to test the hypothesis that inhibiting the autophagy pathway in DCIS will reduce the capacity of DCIS to survive and invade. The study will examine the safety and effectiveness of neoadjuvant chloroquine administration for a one month period to patients with low, intermediate grade, or high grade DCIS. We will evaluate whether this treatment will reduce the capacity of DCIS neoplastic cells, existing within the duct, to survive, induce lesion regression, and kill the invasive DCIS progenitor cells.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a tissue diagnosis of low, intermediate or high grade ductal carcinoma in situ or ductal carcinoma in situ with microinvasion.
  • Patients with ductal carcinoma in situ undergoing either lumpectomy/radiation or mastectomy.
  • Patients must be female at least 18 years of age.
  • Patients must have a signed tissue acquisition consent and have at minimum, adequate samples of primary fresh tissue or blood available for use in this study.
  • No history of a previous invasive cancer in the last five years with the exception of minimally invasive non-melanoma skin cancer.
  • Normal liver function based on Liver Function Tests (Total Bilirubin and AST <1.5 X Upper Limit of Normal).
  • Normal WBC (3.5-10.8 x 103µL), PLT (140-400 x 103µL), and HCT (37-52%)
  • Potassium within the normal range of 3.5-5.3 mEq/L
  • Adequate renal sufficiency (serum creatinine <1.5 mg/dL).
  • ECOG performance status 0-2.
  • Are able to swallow and retain oral medication.
  • No underlying ocular/retinal pathology.
  • No medically documented preexisting auditory damage.
  • Subjects should be willing to abstain from use of hormonal therapies (e.g. hormone replacement therapy, oral contraceptive pills, hormone-containing IUDs, and E-string) and chronic NSAID's for the duration of the study (chronic use of NSAID's is defined as a frequency >3 times/week for more than two weeks per year and includes low dose aspirin).
  • Subjects with child-bearing potential must agree to use adequate contraception (total abstinence (no sexual intercourse), use of condom with spermicide or sterilization surgery, including tubal ligation (tubes tied) or hysterectomy (removal of the uterus or womb)) prior to study entry and for the duration of study treatment phase. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

If a subject is of child-bearing potential (women are considered not of child-bearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have a documented negative serum or urine pregnancy test before starting treatment.

Exclusion Criteria:

  • Patients with a prior history of chemotherapy, hormonal ablation therapy and/or radiation therapy.
  • History of other invasive cancer in the previous 5 years other than minimally invasive non-melanoma skin cancer.
  • Patient desires not to participate in the study.
  • Inability to consent.
  • Current or recent pregnancy (within 12 months),
  • Current use of hormone-containing forms of birth control such as implants (i.e. Norplants, or injectables ( i.e. depo-provera)
  • Currently lactating.
  • Patients with history of renal or hepatic insufficiency.
  • Current diagnosis for depression, including treatment with an SSRI.
  • History of prior treatment with chloroquine for malaria within past 24 months.
  • History of allergic reactions to quinalones or chloroquine.
  • Active diagnosis of psoriasis or currently receiving treatment for psoriasis.
  • History of porphyria.
  • History of known Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency.
  • Alcoholism or hepatic disease.
  • History of epilepsy or seizures in the past 20 years.
  • History of deep vein thrombosis or pulmonary embolism.
  • History of HIV disease and/or treatment with anti-HIV agents.
  • Receiving concurrent treatment with prohibited medications (refer to Table 1 for details on prohibited medications); Examples include: ampicillin, antacids, cimetidine, cyclosporine, kaolin, magnesium trisilicate, coumarin-type anticoagulants, macrolide antibiotics (e.g., clarithromycin, isoniazid, and erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants (e.g. fluoxetine and fluvoxamine), calcium channel blockers (e.g. verapamil and diltiazem), steroids and their modulators (e.g., gestodene, raloxifene, and mifepristone), and several herbal and dietary components (e.g. bergamottin and glabridin).
  • Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01023477

Contacts
Contact: Holly Gallimore 703-776-2688 Holly.Gallimore@inova.org
Contact: Kirsten Edmiston, MD, FACS 703-776-8675 Kirsten.Edmiston@inova.org

Locations
United States, Virginia
Virginia Cancer Specialists, PC Recruiting
Fairfax, Virginia, United States, 22031
Sub-Investigator: Nicholas Robert, MD         
Medical Oncology and Hematology Associates of Northern Virginia Recruiting
Fairfax, Virginia, United States, 22031
Sub-Investigator: Mary Wilkinson, MD         
Virginia Surgery Associates Recruiting
Fairfax, Virginia, United States, 22033
Principal Investigator: Kirsten Edmiston, MD         
Inova Fairfax Hospital Recruiting
Falls Church, Virginia, United States, 22042
Contact: Emil Kamar, BA    703-776-3565    emil.kamar@inova.org   
Principal Investigator: Kirsten Edmiston, MD         
Sponsors and Collaborators
Inova Health Care Services
George Mason University
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Kirsten H Edmiston, MD, FACS Inova Fairfax Hospital Cancer Center
  More Information

No publications provided by Inova Health Care Services

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Inova Health Care Services
ClinicalTrials.gov Identifier: NCT01023477     History of Changes
Other Study ID Numbers: IFHCC 09-002
Study First Received: December 1, 2009
Last Updated: March 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Inova Health Care Services:
Ductal Carcinoma In Situ
Carcinoma, Intraductal, Noninfiltrating
DCIS
Carcinoma, Intraductal
Breast Cancer
Breast Tumors
chloroquine
autophagy
Autophagic Cell Death
Autophagocytosis
Programmed Cell Death, Type II
Autophagy, Cellular
Autophagic Programmed Cell Death

Additional relevant MeSH terms:
Carcinoma, Ductal, Breast
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Chloroquine
Chloroquine diphosphate
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014