Trial Outcomes & Findings for Study of the Efficacy of Chloroquine in the Treatment of Ductal Carcinoma in Situ (The PINC Trial) (NCT NCT01023477)

Last Updated: 2021-06-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

12 participants

Primary outcome timeframe

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

Results posted on

2021-06-29

Participant Flow

Participant milestones

Participant milestones
Measure	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). 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. 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.	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). 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. 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.
Overall Study STARTED	7	5
Overall Study COMPLETED	7	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chloroquine Standard Dose (500mg/Week) n=7 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). 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. 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.	Chloroquine Low Dose (250mg/Week) n=5 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). 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. 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.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Age, Continuous	59 years STANDARD_DEVIATION 6.6 • n=5 Participants	56 years STANDARD_DEVIATION 11.7 • n=7 Participants	58 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants

PRIMARY outcome

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

Population: The analysis population was the number of patients who underwent breast MRI both before and after treatment with chloroquine. (11/12 patients). The population was then further reduced to 10/12 due to the patient with a significant post biopsy hematoma. The extent of the pre-treatment DCIS could not be directly compared due to the presence of a significant hematoma.

Outcome measures

Outcome measures
Measure	Chloroquine Standard Dose (500mg/Week) n=5 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). 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. 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.	Chloroquine Low Dose (250mg/Week) n=5 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). 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. 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.
Average Change in the Longest Diameter of the Breast MRI Target Lesion	6 percentage length change Standard Deviation 19.8	43 percentage length change Standard Deviation 39

SECONDARY outcome

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

Population: Patients who were treated

One of the outcomes was to ensure the safety of weekly chloroquine. Patients were followed clinically during the treatment with chloroquine and during their surgery and postoperative period ( including radiation therapy). Patients were verbally assessed for additional symptoms or concerns. Patients were also examined by the provider during treatment and follow up visits to the surgeon.

Outcome measures

Outcome measures
Measure	Chloroquine Standard Dose (500mg/Week) n=7 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). 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. 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.	Chloroquine Low Dose (250mg/Week) n=5 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). 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. 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.
Total Number of Treatment-Related Adverse Events	0 Adverse Events (mortality, SAE, AE)	0 Adverse Events (mortality, SAE, AE)

SECONDARY outcome

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

Population: The groups were divided by chloroquine dose. Data was only available for 6 out of 12 patients.

We evaluated the effect of therapy on cellular proliferation as measured by the change in proliferating cell nuclear antigen (PCNA) proliferation index. PCNA , which is elevated during the G1/S phase of the cell cycle, may be used as a marker of cellular proliferation. The PCNA proliferation index was measured as the number of PCNA positive stained cells in the DCIS lesion/ total number of cells in the lesion. The change in the PCNA index is equal to the mean PCNA proliferation index pre-treatment minus the mean PCNA proliferation index post-treatment.

Outcome measures

Outcome measures
Measure	Chloroquine Standard Dose (500mg/Week) n=4 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). 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. 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.	Chloroquine Low Dose (250mg/Week) n=2 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). 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. 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.
Effect of Chloroquine on Proliferating Cell Nuclear Antigen (PCNA) Proliferation Index	50.4 Change in PCNA proliferation index Standard Error 7.85	56.71 Change in PCNA proliferation index Standard Error 8.11

SECONDARY outcome

Timeframe: At the time of surgery

Population: The analysis was performed stratifying chloroquine dose.

The study evaluated the effect of chloroquine treatment on the proteomic signaling profiles of the DCIS lesions. Post treatment surgical specimens were evaluated by immunohistochemical staining to measure cell signaling kinase levels for CD68 and HMGB1. CD68 (Cluster Determinant 68) is a marker of macrophages/monocytes in the breast ducts. and HMGB1 (High Mobility Group Box 1) is involved in oxidative stress-mediated autophagy. HMGB1 is a non-histone DNA binding protein. The number of positive cells were quantified and recorded. .

Outcome measures

Outcome measures
Measure	Chloroquine Standard Dose (500mg/Week) n=7 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month standard dose chloroquine (500 mg/week). 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. 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.	Chloroquine Low Dose (250mg/Week) n=5 Participants Patients with ER+ or ER- DCIS regardless of histologic grade will be randomly assigned to receive one month low dose chloroquine (250mg/week). 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. 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.
Impact of Chloroquine Treatment on the Cell Signaling Kinase Levels in DCIS Lesions. HMGB1	33.9 Positive cells Standard Deviation 27.62	47.89 Positive cells Standard Deviation 37.99
Impact of Chloroquine Treatment on the Cell Signaling Kinase Levels in DCIS Lesions. CD68	318.3 Positive cells Standard Deviation 172.3	163.2 Positive cells Standard Deviation 98.2

Adverse Events

Chloroquine Standard Dose (500mg/Week)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Chloroquine Low Dose (250mg/Week)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Kirsten Edmiston, MD

Inova Health Care

Phone: 703-850-9555

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place