Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Anti-Infective Agents

Antirheumatic Agents

All Drugs and Chemicals

Hydroxychloroquine

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

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.

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.

Brian Wolpin, MD, MPH

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

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.

Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

Phase II Study of Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

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.

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 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 estimated using Kaplan-Meier (KM) methods is defined as the time from study entry to death or date last known alive.

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.

All grade 4-5 adverse events with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms.

Brigham and Women's Hospital

Massachusetts General Hospital

Dana-Farber Cancer Institute

Principal Investigator

Maximum grade toxicity by type for a patient over time including only treatment-related events (possible, probable or definite attribution) was first calculated with patients therefore appearing once for a given type of toxicity. Serious and Other AEs were defined as events of grades 3-5 and grades 1-2, respectively, based on CTCAEv3.

Hydroxychloroquine 400 mg b.i.d.

Hydroxychloroquine 600 mg b.i.d.

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

ECOG PS0: Fully active, able to carry on all pre-disease performance without restriction ECOG PS1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature ECOG PS2: Ambulatory and capable of all self-care but unable to carry out any work activities; Up and about more than 50% of waking hours

ECOG Performance Status (PS)

Head or Head and Body

Body or Tail

Site of Primary Tumor

Liver

Lung

Peritoneum

Other

Location of Metastasis

The analysis dataset is comprised of all enrolled patients.

Brian M. Wolpin

2-month Progression-Free Survival Rate

Biochemical response could not be estimated due to insufficient longitudinal CA 19-9 measurements. This was directly related to the observed lack of activity of the study drug and corresponding short duration of therapy.

Spots Global Cancer Trial Database for Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial