Completed

NCT Number: NCT01634893

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.

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Key information

Conditions

Refractory or Relapsed Solid Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cancer Therapy and Research Center at UTHSCSA

San Antonio, Texas, 78229, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Sorafenib combined with Hydroxychloroquine

Drug

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.

Primary outcomes

Toxicity evaluated according to the common toxicity criteria for adverse events (AEs) (CTCAEv4.0)

Time frame: 2 years

To assess the toxicities of combining sorafenib plus HCQ in this patient population

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center at San Antonio

Other

Registry information

Official study title

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

Important dates

Study start: 2012
Primary completion: 2015
Study completion: 2015
First posted: Jul 6, 2012
Registry last updated: Mar 25, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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