Hydroxychloroquine In Previously Treated Patients With Metastatic Pancreatic Cancer

Study Overview

Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

Hydroxychloroquine is approved for the treatment of non-cancerous illnesses such as rheumatoid arthritis and systemic lupus erythematous. Researchers in the laboratory have tested tumors from patients with pancreatic cancer and have discovered that they have certain pathways inside the cells that promote growth and survival of the tumor. Hydroxychloroquine may inactivate these pathways and results in the death of pancreatic cancer cells.

Primary Objective * To determine the efficacy of single-agent hydroxychloroquine in patients with metastatic pancreatic cancer previously treated with one or two prior chemotherapy regimens as measured by progression-free survival at two months Secondary Objectives * To assess tumor response rate, biochemical response rate (i.e. decrease in serum CA19-9 by > 30%), and overall survival Translational/Exploratory Objectives * To investigate predictors of response to anti-autophagy therapy with hydroxychloroquine * To explore the kinetics of in vivo autophagy inhibition using peripheral blood WBCs to monitor autophagic activity among patients receiving hydroxychloroquine

Pancreatic Cancer

DRUG: Hydroxychloroquine

10-310

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-01-07	Results First Submitted 2017-04-11	Last Update Submitted that met QC Criteria 2017-05-19
First Submitted that Met QC Criteria 2011-01-07	Results First Submitted that Met QC Criteria 2017-05-19	Last Update Posted (ACTUAL) 2017-06-14
First Posted (ACTUAL) 2011-01-11	Results First Posted 2017-06-14	Last Verified 2017-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Hydroxychloroquine 400 mg b.i.d. Patients received 400 mg hydroxychloroquine orally twice per day. Cycle duration was 4 weeks. Patients remained on treatment indefinitely without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation pe	DRUG: Hydroxychloroquine
EXPERIMENTAL: Hydroxychloroquine 600 mg b.i.d. Patients received 600 mg hydroxychloroquine orally twice per day. Cycle duration was 4 weeks. Patients remained on treatment indefinitely without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation pe	DRUG: Hydroxychloroquine

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Hydroxychloroquine 400 mg b.i.d.

Patients received 400 mg hydroxychloroquine orally twice per day. Cycle duration was 4 weeks. Patients remained on treatment indefinitely without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation pe

DRUG: Hydroxychloroquine

EXPERIMENTAL: Hydroxychloroquine 600 mg b.i.d.

Patients received 600 mg hydroxychloroquine orally twice per day. Cycle duration was 4 weeks. Patients remained on treatment indefinitely without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation pe

DRUG: Hydroxychloroquine

Primary Outcome Measures	Measure Description	Time Frame
2-month Progression-Free Survival Rate	2-month progression-free survival rate was defined as the percentage of patients absent progression (PD) or death before 2 months. Patients were considered to have experienced PD if they demonstrated either clinical deterioration resulting in withdrawal or PD per RECIST 1.0 criteria: At least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.	Disease was evaluated radiologically at baseline and at the first restaging at 2 months.

Secondary Outcome Measures	Measure Description	Time Frame
Biochemical Response Rate	Biochemical response rate was defined as the percentage of patients achieving on treatment a decrease in serum CA 19-9 by > 30% from baseline.	Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days.
Tumor Response Rate	Tumor response rate is the percentage of patients achieving complete or partial response on treatment based on RECIST 1.0 criteria. For target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR for the evaluation of non-target lesions is the disappearance of non-target lesions and normalization of tumor marker level. Appearance of one or more new lesions is classified as progression of non-target lesions. CR or PR confirmation is required >/= 4 weeks.	Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days.
Overall Survival	Overall survival estimated using Kaplan-Meier (KM) methods is defined as the time from study entry to death or date last known alive.	All patients were followed until death. Median survival follow-up in this study cohort was 60 days (95% CI: 40-184).
Progression-Free Survival	Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to time of objective progression on CT scan or the time of death for patients with clinical deterioration resulting in withdrawal from the trial. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Patients without an event were censored at date of last disease evaluation.	Disease was evaluated radiologically at baseline and every 2 months on treatment. Median PFS follow-up in this study cohort was 46.5 days (95% CI 33-61).
Grade 4-5 Treatment-Related Toxicity	All grade 4-5 adverse events with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms.	Adverse events were assessed each cycle throughout treatment. Participants were followed for the duration of treatment, an average of 34 days for this study population.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically confirmed unresectable pancreatic adenocarcinoma that is metastatic to distant sites
Measurable disease, defined as at least one lesion that can accurately be measured in at least one dimension
Patients must have been treated with one or two previous lines of chemotherapy for metastatic disease with documented tumor progression or intolerance due to toxicity
Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
18 years of age or older
Life expectancy of greater than 12 weeks
ECOG performance status of 0, 1 or 2
Normal organ and marrow function as outlined in the protocol
Patients must be able to swallow pills
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
More than two previous chemotherapy regimens for the treatment of metastatic pancreatic cancer
Uncontrolled brain or leptomeningeal metastases
History of macular degeneration, visual field changes, retinal disease, or cataracts that would interfere with funduscopic eye examinations
History of allergic reactions attributed to compounds of similar chemical or biologic composition to hydroxychloroquine
Previous treatment with chloroquine or hydroxychloroquine for other indications, such as rheumatoid arthritis, SLE or malaria prophylaxis
Prior treatment with any investigational drug within the preceding 4 weeks
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter absorption of hydroxychloroquine. Patients who have undergone a Whipple procedure for localized pancreatic cancer are not excluded from enrollment
History of non-compliance to medical regimens
Known diagnosis of glucose-6-phosphate deficiency, porphyria or psoriasis
Penicillamine use for Wilson's disease or any other indication
Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or breastfeeding women
Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3-years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past three years: cervical cancer in situ, and basal cell or squamous cell carcinoma
HIV-positive individuals on combination antiretroviral therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Brigham and Women's Hospital
Massachusetts General Hospital

Investigators

PRINCIPAL_INVESTIGATOR: Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Wolpin BM, Rubinson DA, Wang X, Chan JA, Cleary JM, Enzinger PC, Fuchs CS, McCleary NJ, Meyerhardt JA, Ng K, Schrag D, Sikora AL, Spicer BA, Killion L, Mamon H, Kimmelman AC. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist. 2014 Jun;19(6):637-8. doi: 10.1634/theoncologist.2014-0086. Epub 2014 May 12.

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