Hydroxychloroquine in Previously Treated Patients With Metastatic Pancreatic Cancer

NCT01273805 | Completed Phase 2 Results DMC

• 1 other identifier: 10-310
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Pancreatic Cancer

Keywords

metastatic pancreatic cancer; hydroxychloroquine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Biochemical Response Rate

  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

  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

  All patients were followed until death. Median survival follow-up in this study cohort was 60 days (95% CI: 40-184).

• Progression-Free Survival

  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

  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.

Study Arms (2)

Hydroxychloroquine 400 mg b.i.d.

EXPERIMENTAL

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

Hydroxychloroquine 600 mg b.i.d.

EXPERIMENTAL

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

Interventions

Hydroxychloroquine DRUG

Also known as: Plaquenil

Hydroxychloroquine 400 mg b.i.d.; Hydroxychloroquine 600 mg b.i.d.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Related Publications (1)

• 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.

  PMID: 24821822 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Brian M. Wolpin
• Organization: Dana-Farber Cancer Institute

Brian_Wolpin@dfci.harvard.edu

617.632.6942

Study Officials

• Brian Wolpin, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: January 7, 2011
• First Posted: January 11, 2011
• Study Start: January 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: February 1, 2014
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)