Clinical trial NCT01273805: Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer
Official title: Phase II Study of Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: metastatic pancreatic cancer
hydroxychloroquine
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
First posted: 2011-01-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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

Eligibility 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

Primary outcomes:
measure: 2-month Progression-Free Survival Rate
timeFrame: Disease was evaluated radiologically at baseline and at the first restaging at 2 months.
Secondary outcomes:
measure: Biochemical Response Rate
timeFrame: Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days.
measure: Tumor Response Rate
timeFrame: Disease was evaluated radiologically at baseline and every 2 months on treatment. Median duration of treatment for this study cohort was 34 days.
measure: Overall Survival
timeFrame: All patients were followed until death. Median survival follow-up in this study cohort was 60 days (95% CI: 40-184).
measure: Progression-Free Survival
timeFrame: 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).
measure: Grade 4-5 Treatment-Related Toxicity
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Brian Wolpin, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.