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

• ClinicalTrials.gov Identifier: NCT01023477
• Recruitment Status: Completed
• First Posted: December 2, 2009
• Last Update Posted: March 8, 2017
• Sponsor: Inova Health Care Services
• 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

Study Description

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.

Condition or disease	Intervention/treatment	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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Preventing Invasive Breast Neoplasia With Chloroquine (PINC) Trial
• Study Start Date: December 2009
• Actual Primary Completion Date: October 2016
• Actual Study Completion Date: October 2016

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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. ]

Secondary Outcome Measures :

1. Evaluate the safety and dosing efficacy of chloroquine in the treatment of patients with DCIS. [ Time Frame: Continually ]
2. 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. ]
3. 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. ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes 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

Locations

United States, Virginia

Medical Oncology and Hematology Associates of Northern Virginia

Fairfax, Virginia, United States, 22031

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States, 22031

Virginia Surgery Associates

Fairfax, Virginia, United States, 22033

Inova Fairfax Hospital

Falls Church, Virginia, United States, 22042

Sponsors and Collaborators

Inova Health Care Services

George Mason University

University of Pittsburgh

United States Department of Defense

U.S. Army Medical Research and Development Command

Investigators

• Principal Investigator: Kirsten H Edmiston, MD, FACS; Inova Fairfax Hospital Cancer Center
• Principal Investigator: Priscilla McAuliffe, MD, PhD; Magee-Women's Hospital of UPMC

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Inova Health Care Services
• ClinicalTrials.gov Identifier: NCT01023477
• Other Study ID Numbers: IFHCC 09-002
• First Posted: December 2, 2009
• Last Update Posted: March 8, 2017
• Last Verified: March 2017

Keywords provided by Inova Health Care Services:

Breast Cancer; Breast Tumors; chloroquine; Carcinoma, Intraductal, Noninfiltrating; Ductal Carcinoma In Situ; DCIS; Carcinoma, Intraductal; autophagy; Autophagic Cell Death; Autophagocytosis; Programmed Cell Death, Type II; Autophagy, Cellular; Autophagic Programmed Cell Death

Additional relevant MeSH terms:

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Chloroquine; Chloroquine diphosphate; Carcinoma; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Adenocarcinoma; Amebicides; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Antimalarials; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Filaricides; Antinematodal Agents; Anthelmintics