Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors

A Phase I Dose-Escalation Trial of Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors

Patients with recurrent, refractory or metastatic solid tumors have a dismal prognosis with few viable treatment options. Hydroxychloroquine (HCQ) is an agent that has been widely used to treat malaria. Because HCQ also inhibits autophagy, a process central to survival of cancer in the face of metabolic stress, including the effects of anti-cancer therapy, it is now in human cancer trials combined with other agents to attempt to boost the efficacy of those agents. Autophagy inhibition improves the activity of sorafenib in hepatocellular carcinoma.

Sorafenib is an oral multi-kinase inhibitor that blocks not only receptor tyrosine kinases such as KIT, VEGFR and PDGFR but also serine/threonine kinases along the RAS/RAF/MEK/ERK pathway.

The investigators propose to treat patients with refractory or relapsed solid tumors with sorafenib, to boost its efficacy while attempting to mitigate its toxicity by combining with HCQ.

Study Overview

• Status: Completed
• Conditions: Refractory or Relapsed Solid Tumors
• Intervention / Treatment: Drug: Sorafenib combined with Hydroxychloroquine

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center at UTHSCSA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to provide informed consent
• Not on immune-modulating drugs, except those used as study drug premedication, unless the principal investigator grants an exception (which exception must be documented in writing)
• Patients with relapsed or refractory solid tumors with no viable treatment options
• Measurable disease within 30 days of study enrollment
• Blood hemoglobin > 8.5 gm/dl within 7 days of study enrollment
• Absolute neutrophil count > 1000/mm3 within 7 days of study enrollment
• Platelet count > 50,000/mm3 within 7 days of study enrollment
• SGOT <10x upper limit of normal within 7 days of study enrollment
• No chemotherapy or radiation therapy in the 14 days prior to initiation of treatment on this study. No other concurrent chemotherapy, surgery or radiation therapy during this protocol except surgery or radiation therapy to control symptoms with concurrence of the principal investigator.
• No contraindication to any study treatment
• No active major medical problems, including untreated or uncontrolled infections
• If of reproductive potential, a negative urine or blood pregnancy test within 3 days of study enrollment, and agreement to use adequate contraception. In relevant subjects, pregnancy testing will continue monthly while on treatment unless the subject is no longer able to become pregnant or there is sufficient justification otherwise
• Not breast feeding
• Life expectancy > 6 months
• ECOG performance status < 2
• Age 18+ years
• No active substance abuse in the prior 6 months
• Not on digoxin or cimetidine

Exclusion Criteria:

• Contraindication or hypersensitivity to any study drug or its components or excipients
• Current pregnancy or breast feeding
• Inability to document adequate contraception if a female of reproductive potential
• Chemotherapy or radiation therapy within the 14 days prior to initiation of study treatment
• Prior treatment with sorafenib. Prior HCQ use is not an exclusion.
• Life expectancy < 6 months
• ECOG performance status > 2
• Symptomatic coronary artery disease (including uncontrolled angina, congestive heart failure, and the like)
• Uncontrolled hypertension (diastolic BP consistently >100 mm Hg or systolic BP consistently >160 mm Hg on a regular basis)
• Uncontrolled, symptomatic cardiac arrhythmia
• Active substance abuse in the prior 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib plus Hydroxychloroquine; Dose escalation of sorafenib combined with hydroxychloroquine (HCQ) to a maximum of sorafenib 400 mg PO BID plus HCQ 400 mg PO QD. Drugs are given on an intermittent schedule of days 1-5/week in a 28-day cycle. Sorafenib alone is given in cycle 1, and HCQ is added in cycle 2.	Drug: Sorafenib combined with Hydroxychloroquine; dose escalation of sorafenib combined with hydroxychloroquine (HCQ) to a maximum of sorafenib 400 mg PO BID plus HCQ 400 mg PO QD. Drugs are given on an intermittent schedule of days 1-5/week in a 28-day cycle. Sorafenib alone is given in cycle 1, and HCQ is added in cycle 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity evaluated according to the common toxicity criteria for adverse events (AEs) (CTCAEv4.0)	To assess the toxicities of combining sorafenib plus HCQ in this patient population	2 years

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Tyler Curiel, MD, MPH, University of Texas Health Science Center San Antonio

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 3, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Estimate): March 25, 2016
• Last Update Submitted That Met QC Criteria: March 24, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Refractory or Relapsed Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Protein Kinase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Sorafenib; Hydroxychloroquine
• Other Study ID Numbers: CTRC 11-71; HSC20120203H (Other Identifier: UTHSCSA IRB)