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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by The University of Texas Health Science Center at San Antonio
Sponsor:
Information provided by (Responsible Party):
Tyler Curiel, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01634893
First received: July 3, 2012
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Refractory or Relapsed Solid Tumors
Drug: Sorafenib combined with Hydroxychloroquine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose-Escalation Trial of Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To assess the toxicities of combining sorafenib plus HCQ in this patient population

  • Maximum tolerated dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To define the Maximum Tolerated Dose (MTD) of sorafenib plus HCQ in this patient population


Secondary Outcome Measures:
  • Objective Tumor Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To estimate the proportion of patients with measurable disease who have objective tumor responses by treatment. Determination of response should take into consideration all target and non-target lesions and, if appropriate, CA-125.


Estimated Enrollment: 24
Study Start Date: June 2012
Estimated Study Completion Date: July 2022
Estimated Primary Completion Date: July 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01634893

Locations
United States, Texas
Cancer Therapy and Research Center at UTHSCSA Recruiting
San Antonio, Texas, United States, 78229
Contact: Epp Goodwin    210-450-5798    onctrial@idd.org   
Principal Investigator: Tyler Curiel, MD, MPH         
Sponsors and Collaborators
Tyler Curiel
Investigators
Principal Investigator: Tyler Curiel, MD, MPH University of Texas Health Science Center San Antonio
  More Information

No publications provided

Responsible Party: Tyler Curiel, Principal Investigator, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01634893     History of Changes
Other Study ID Numbers: CTRC 11-71, HSC20120203H
Study First Received: July 3, 2012
Last Updated: September 17, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at San Antonio:
Refractory or Relapsed Solid Tumors

Additional relevant MeSH terms:
Neoplasms
Hydroxychloroquine
Sorafenib
Anti-Infective Agents
Antimalarials
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014