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

NCT01023477 | Completed Phase 1 Results DMC

• 1 other identifier: IFHCC 09-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 4

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.

Conditions

Carcinoma, Intraductal, Noninfiltrating; DCIS; Ductal Carcinoma In Situ

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Average Change in the Longest Diameter of the Breast MRI Target Lesion

  One of the primary outcomes of this study was to measure the impact of weekly chloroquine on the amount of DCIS seen on MRI.The tumor response was evaluated by RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR The longest diameter of the target lesion or primary area of non-mass enhancement was measured by digital calipers. For one patient, the longest diameter was difficult to measure due to the presence of a significant post biopsy resolving hematoma at the biopsy site. Further correlation was made based on the extent of the pre-treatment microcalcifications and post treatment areas of non-mass enhancement.

  Immediately preceding study drug treatment and again after treatment prior to surgery. The total time interval was up to 8 weeks

Secondary Outcomes (3)

• Total Number of Treatment-Related Adverse Events

  The patients were monitored from the time of diagnosis through 6 months of surgical follow up.

• Effect of Chloroquine on Proliferating Cell Nuclear Antigen (PCNA) Proliferation Index

  At the time of breast biopsy and again at time of surgery.

• Impact of Chloroquine Treatment on the Cell Signaling Kinase Levels in DCIS Lesions.

  At the time of surgery

Study Arms (2)

Chloroquine Standard Dose (500mg/week)

EXPERIMENTAL

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); Procedure: Breast Biopsy

Chloroquine Low Dose (250mg/week)

EXPERIMENTAL

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); Procedure: Breast Biopsy

Interventions

Chloroquine Standard Dose (500mg/week) DRUG

Patients will receive chloroquine (500 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.

Also known as: Aralen

Chloroquine Standard Dose (500mg/week)

Chloroquine Low Dose (250mg/week) DRUG

Patients will receive chloroquine (250 mg/once a week) for 1 month prior to surgical removal of the DCIS lesion.

Also known as: Aralen

Chloroquine Low Dose (250mg/week)

Breast Biopsy PROCEDURE

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.

Also known as: Biopsy, DCIS, Ductal Carcinoma in Situ

Chloroquine Low Dose (250mg/week); Chloroquine Standard Dose (500mg/week)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Asparate transaminase (AST) \<1.5 X Upper Limit of Normal).
• Normal White Blood Count (WBC) (3.5-10.8 x 103µL), Platelet count (PLT) (140-400 x 103µL), and Hematocrit (HCT)(37-52%)
• Potassium within the normal range of 3.5-5.3 mEq/L
• Adequate renal sufficiency (serum creatinine \<1.5 mg/dL).
• Eastern Cooperative Oncology Group 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 Intra Uterine Device (IUD)s, and E-string) and chronic non-steroidal anti-inflammatory (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.

You may not qualify if:

• 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 Selective Serotonin Reuptake Inhibitor (SSRI).
• History of prior treatment with chloroquine for malaria within past 24 months.
• History of allergic reactions to quinolones 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.

Sponsors & Collaborators

• Inova Health Care Services: lead
• George Mason University: collaborator
• University of Pittsburgh Medical Center: collaborator
• United States Department of Defense: collaborator
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (4)

Medical Oncology and Hematology Associates of Northern Virginia

Fairfax, Virginia, 22031, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Virginia Surgery Associates

Fairfax, Virginia, 22033, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Related Publications (1)

• 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. doi: 10.4161/cc.9.12.12048. Epub 2010 Jun 15.

  PMID: 20562526 DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating; Breast Neoplasms

Interventions

Chloroquine; Biopsy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Kirsten Edmiston, MD
• Organization: Inova Health Care

Kirsten.edmiston@inova.org

703-850-9555

Study Officials

• Kirsten H Edmiston, MD, FACS

  Inova Fairfax Hospital Cancer Center

  PRINCIPAL INVESTIGATOR

• Priscilla McAuliffe, MD, PhD

  Magee-Women's Hospital of UPMC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 2, 2009
• Study Start: December 1, 2009
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-05

Locations

US (4)