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Sirolimus or Vorinostat and Hydroxychloroquine in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: December 22, 2010
Last updated: April 25, 2016
Last verified: April 2016
The goal of this clinical research study is to find the highest tolerable dose of sirolimus or vorinostat that can be given in combination with hydroxychloroquine to patients with advanced cancer. The safety of these drug combinations will also be studied.

Condition Intervention Phase
Advanced Cancers
Drug: Hydroxychloroquine
Drug: Sirolimus
Drug: Vorinostat
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Sirolimus (mTOR Inhibitor) or Vorinostat (HDAC Inhibitor) in Combination With Hydroxychloroquine (Autophagy Inhibitor) in Patients With Advanced Malignancies

Resource links provided by NLM:

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Sirolimus or Vorinostat in Combination with Hydroxychloroquine [ Time Frame: 21 day cycles, approximately 4 weeks for DLT assessment ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) defined defined as the dose level below the dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT) in the first treatment cycle.

Estimated Enrollment: 236
Study Start Date: April 2011
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hydroxychloroquine + Sirolimus
Hydroxychloroquine starting dose of 200 mg by mouth every day for a 21 day cycle. Sirolimus starting dose of 2 mg by mouth every day for a 21 day cycle.
Drug: Hydroxychloroquine
Starting dose of 200 mg by mouth every day for a 21 day cycle.
Other Name: Plaquenil
Drug: Sirolimus
Starting dose of 2 mg by mouth every day for a 21 day cycle.
Other Name: Rapamune
Experimental: Hydroxychloroquine + Vorinostat
Hydroxychloroquine starting dose of 200 mg by mouth every day for a 21 day cycle. Vorinostat starting dose of 200 mg by mouth per day for a 21 day cycle.
Drug: Hydroxychloroquine
Starting dose of 200 mg by mouth every day for a 21 day cycle.
Other Name: Plaquenil
Drug: Vorinostat
Starting dose of 200 mg by mouth per day for a 21 day cycle.
Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with advanced or metastatic cancers that are refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
  2. Patients must be >/= 18 years.
  3. Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment provided that radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
  4. ECOG performance status </= 2
  5. Patients must have adequate organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL;platelets >/=50,000/mL; creatinine </= 2 X ULN; total bilirubin </= 2.0 (exceptions may apply to benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome); ALT(SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN;cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL (sirolimus and hydroxychloroquine only).
  6. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
  7. Patients must be able to understand and be willing to sign a written informed consent document.

Exclusion Criteria:

  1. Uncontrolled intercurrent illness, including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
  2. Pregnant or lactating women.
  3. History of hypersensitivity to sirolimus.
  4. History of hypersensitivity to vorinostat
  5. History of hypersensitivity to hydroxychloroquine
  6. History of hypersensitivity to any component of the formulation.
  7. Patients unwilling or unable to sign informed consent document.
  8. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
  9. Patients with known glucose-6-phosphate dehydrogenase deficiency.
  10. Patients with porphyria cutanea tarda.
  11. Patients with psoriasis.
  12. Patients with pre-existing maculopathy or retinopathy of the eye.
  13. Patients who have a pre-existing myopathy.
  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 identifier: NCT01266057

Contact: Filip Janku, MD, PHD 713-563-2632

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Filip Janku, MD,PHD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Filip Janku, MD, PHD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01266057     History of Changes
Other Study ID Numbers: 2010-0588  NCI-2011-00303 
Study First Received: December 22, 2010
Last Updated: April 25, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Malignancies
Metastatic cancers
Suberoylanilide Hydroxamic Acid

Additional relevant MeSH terms:
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents processed this record on October 21, 2016