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Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Information provided by (Responsible Party):
Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01273805
First received: January 7, 2011
Last updated: May 19, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Pancreatic Cancer Drug: Hydroxychloroquine Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
There were 2 arms in this study because the study was amended to evaluate a second cohort of patients treated at a higher dose using the same two-stage statistical design.
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase II Study of Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 2-month Progression-Free Survival Rate [ Time Frame: Disease was evaluated radiologically at baseline and at the first restaging at 2 months. ]
    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.


Secondary Outcome Measures:
  • Biochemical Response Rate [ Time Frame: Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days. ]
    Biochemical response rate was defined as the percentage of patients achieving on treatment a decrease in serum CA 19-9 by > 30% from baseline.

  • Tumor Response Rate [ Time Frame: 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 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.

  • Overall Survival [ Time Frame: All patients were followed until death. Median survival follow-up in this study cohort was 60 days (95% CI: 40-184). ]
    Overall survival estimated using Kaplan-Meier (KM) methods is defined as the time from study entry to death or date last known alive.

  • Progression-Free Survival [ Time Frame: 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). ]
    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.

  • Grade 4-5 Treatment-Related Toxicity [ Time Frame: 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. ]
    All grade 4-5 adverse events with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms.


Enrollment: 20
Actual Study Start Date: January 2011
Study Completion Date: February 2014
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 per MD decision.
Drug: Hydroxychloroquine
Other Name: Plaquenil
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 per MD decision.
Drug: Hydroxychloroquine
Other Name: Plaquenil

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01273805

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02214
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Investigators
Principal Investigator: Brian Wolpin, MD, MPH Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Brian Wolpin, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01273805     History of Changes
Other Study ID Numbers: 10-310
Study First Received: January 7, 2011
Results First Received: April 11, 2017
Last Updated: May 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute:
metastatic pancreatic cancer
hydroxychloroquine

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Hydroxychloroquine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 19, 2017