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Sirolimus or Vorinostat and Hydroxychloroquine in Advanced Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01266057
First Posted: December 24, 2010
Last Update Posted: July 14, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  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
Intervention Model: Single Group Assignment
Masking: None (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 in Participants with Advanced Cancers [ Time Frame: 21 day cycles, approximately 4 weeks for DLT assessment ]

    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.

    Dose limiting toxicity (DLT) defined as: Any grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0 that is possibly, probably or definitely related to any of the three study medications, even if expected. This is to include symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE that is possibly, probably or definitely related to the therapy.



Secondary Outcome Measures:
  • Antitumor Efficacy of Sirolimus or Vorinostat in Combination with Hydroxychloroquine in Participants with Advanced Cancers [ Time Frame: 6 weeks ]
    Participants with lymphoma measured per the WHO criteria,68 and all others evaluated using RECIST 1.1 criteria.69.


Enrollment: 143
Actual Study Start Date: April 28, 2011
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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 (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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01266057


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

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01266057     History of Changes
Other Study ID Numbers: 2010-0588
NCI-2011-00303 ( Registry Identifier: NCI CTRP )
First Submitted: December 22, 2010
First Posted: December 24, 2010
Last Update Posted: July 14, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Sirolimus
Everolimus
Hydroxychloroquine
Vorinostat
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
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Antirheumatic Agents