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Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT01273805
Recruitment Status : Completed
First Posted : January 11, 2011
Results First Posted : June 14, 2017
Last Update Posted : June 14, 2017
Sponsor:
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Information provided by (Responsible Party):
Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute

Tracking Information
First Submitted Date  ICMJE January 7, 2011
First Posted Date  ICMJE January 11, 2011
Results First Submitted Date  ICMJE April 11, 2017
Results First Posted Date  ICMJE June 14, 2017
Last Update Posted Date June 14, 2017
Actual Study Start Date  ICMJE January 2011
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2011)
Progression-Free Survival [ Time Frame: 2 years ]
To assess progression-free survivial at two months among patients with metastatic pancreatic cancer receiving single-agent hydroxychloroquine.
Change History Complete list of historical versions of study NCT01273805 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2011)
Biochemical Response Rate [ Time Frame: 2 years ]
Biochemical response rate (i.e. decrease in serum CA 19-9 by > 30%) in this patient population
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer
Official Title  ICMJE Phase II Study of Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer
Brief Summary 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.
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE Drug: Hydroxychloroquine
Other Name: Plaquenil
Study Arms  ICMJE
  • 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.
    Intervention: 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 per MD decision.
    Intervention: Drug: Hydroxychloroquine
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 19, 2017)
20
Original Estimated Enrollment  ICMJE
 (submitted: January 7, 2011)
35
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01273805
Other Study ID Numbers  ICMJE 10-310
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Brian Wolpin, MD, MPH, Dana-Farber Cancer Institute
Study Sponsor  ICMJE Dana-Farber Cancer Institute
Collaborators  ICMJE
  • Brigham and Women's Hospital
  • Massachusetts General Hospital
Investigators  ICMJE
Principal Investigator: Brian Wolpin, MD, MPH Dana-Farber Cancer Institute
PRS Account Dana-Farber Cancer Institute
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP