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

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ClinicalTrials.gov Identifier: NCT01023477
Recruitment Status : Completed
First Posted : December 2, 2009
Last Update Posted : March 8, 2017
Sponsor:
Collaborators:
George Mason University
University of Pittsburgh
United States Department of Defense
U.S. Army Medical Research and Development Command
Information provided by (Responsible Party):
Inova Health Care Services

Tracking Information
First Submitted Date  ICMJE December 1, 2009
First Posted Date  ICMJE December 2, 2009
Last Update Posted Date March 8, 2017
Study Start Date  ICMJE December 2009
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01023477 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2011)
  • Evaluate the safety and dosing efficacy of chloroquine in the treatment of patients with DCIS. [ Time Frame: Continually ]
  • 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. ]
  • 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. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2009)
Evaluate the safety of combined chloroquine and tamoxifen therapy (relevant only for combined chloroquine and tamoxifen arm). [ Time Frame: Continually ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of the Efficacy of Chloroquine in the Treatment of Ductal Carcinoma in Situ (The PINC Trial)
Official Title  ICMJE Preventing Invasive Breast Neoplasia With Chloroquine (PINC) Trial
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Intraductal, Noninfiltrating
  • DCIS
  • Ductal Carcinoma In Situ
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Chloroquine Standard Dose (500mg/week)
    • Procedure: Breast Biopsy
  • 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).
    Interventions:
    • Drug: Chloroquine Low Dose (250mg/week)
    • Procedure: Breast Biopsy
Publications * Martinez-Outschoorn UE, Pavlides S, Whitaker-Menezes D, Daumer KM, Milliman JN, Chiavarina B, Migneco G, Witkiewicz AK, Martinez-Cantarin MP, Flomenberg N, Howell A, Pestell RG, Lisanti MP, Sotgia F. Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: implications for breast cancer and DCIS therapy with autophagy inhibitors. Cell Cycle. 2010 Jun 15;9(12):2423-33. Epub 2010 Jun 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 23, 2016)
12
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2009)
90
Actual Study Completion Date  ICMJE October 2016
Actual Primary Completion Date October 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01023477
Other Study ID Numbers  ICMJE IFHCC 09-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Inova Health Care Services
Study Sponsor  ICMJE Inova Health Care Services
Collaborators  ICMJE
  • George Mason University
  • University of Pittsburgh
  • United States Department of Defense
  • U.S. Army Medical Research and Development Command
Investigators  ICMJE
Principal Investigator: Kirsten H Edmiston, MD, FACS Inova Fairfax Hospital Cancer Center
Principal Investigator: Priscilla McAuliffe, MD, PhD Magee-Women's Hospital of UPMC
PRS Account Inova Health Care Services
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP