Sirolimus or Vorinostat and Hydroxychloroquine in Advanced Cancer

NCT01266057 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2010-0588NCI-2011-00303
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Cancers

Keywords

Advanced Malignancies; Metastatic cancers; Sirolimus; Hydroxychloroquine; Vorinostat; Plaquenil; Rapamune; Saha; Suberoylanilide Hydroxamic Acid; MSK-390; Zolinza

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Sirolimus or Vorinostat in Combination with Hydroxychloroquine in Participants with Advanced Cancers

  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.

  21 day cycles, approximately 4 weeks for DLT assessment

Secondary Outcomes (1)

• Antitumor Efficacy of Sirolimus or Vorinostat in Combination with Hydroxychloroquine in Participants with Advanced Cancers

  6 weeks

Study Arms (2)

Hydroxychloroquine + Sirolimus

EXPERIMENTAL

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; Drug: Sirolimus

Hydroxychloroquine + Vorinostat

EXPERIMENTAL

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; Drug: Vorinostat

Interventions

Hydroxychloroquine DRUG

Starting dose of 200 mg by mouth every day for a 21 day cycle.

Also known as: Plaquenil

Hydroxychloroquine + Sirolimus; Hydroxychloroquine + Vorinostat

Sirolimus DRUG

Starting dose of 2 mg by mouth every day for a 21 day cycle.

Also known as: Rapamune

Hydroxychloroquine + Sirolimus

Vorinostat DRUG

Starting dose of 200 mg by mouth per day for a 21 day cycle.

Also known as: SAHA, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza

Hydroxychloroquine + Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients must be \>/= 18 years.
• 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).
• ECOG performance status \</= 2
• 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).
• 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.
• Patients must be able to understand and be willing to sign a written informed consent document.

You may not qualify if:

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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Neoplasms

Interventions

Hydroxychloroquine; Sirolimus; Vorinostat

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Filip Janku, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2010
• First Posted: December 24, 2010
• Study Start: April 28, 2011
• Primary Completion: February 11, 2021
• Study Completion: February 11, 2021
• Last Updated: March 4, 2021

Record last verified: 2021-03

Locations

US (1)