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Sirolimus or Vorinostat and Hydroxychloroquine in Advanced Cancer

This study is currently recruiting participants.
Verified May 2013 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01266057
First received: December 22, 2010
Last updated: May 3, 2013
Last verified: May 2013
History of Changes
  Purpose

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:

MedlinePlus related topics: Cancer
U.S. FDA Resources

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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 21 day cycles, approximaely 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 2015 (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

  Eligibility

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

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; 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01266057

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

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

Additional Information:
UT MD Anderson Cancer Center website  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01266057     History of Changes
Other Study ID Numbers: 2010-0588
Study First Received: December 22, 2010
Last Updated: May 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Malignancies
Metastatic cancers
Sirolimus
Hydroxychloroquine
Vorinostat
Plaquenil
 Rapamune
Saha
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza

Additional relevant MeSH terms:
Neoplasms
Hydroxychloroquine
Vorinostat
Sirolimus
Everolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antimalarials
 Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Histone Deacetylase Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013