Trial record 1 of 1 for:    NCT01087554
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Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01087554
First received: March 15, 2010
Last updated: May 13, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of the combination vorinostat given in combination with either sirolimus, everolimus or temsirolimus that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.


Condition Intervention Phase
Advanced Cancer
Drug: Sirolimus
Drug: Vorinostat
Drug: Everolimus
Drug: Temsirolimus
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Sirolimus or Everolimus or Temsirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) defined by dose-limiting toxicities (DLTs) that 1) occur during the first four weeks of therapy, 2) are related to the study medications (attributions: possible, probable, and likely) and 3) fulfill one of the following criteria (as graded by the NCI Common Terminology Criteria for Adverse Events). MTD is defined as highest dose level in which 6 patients have been treated with less than 2 DLTs.


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: After 4, 28 day cycles ] [ Designated as safety issue: No ]

    Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    Progressive Disease (PD): at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

    Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.



Estimated Enrollment: 249
Study Start Date: March 2010
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Vorinostat + Sirolimus

Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.

Expansion Phase starting dose: MTD from Escalation Phase.

Escalation Phase: Sirolimus starting dose1 mg by mouth on Days 1 - 28.

Expansion Phase starting dose: MTD from Escalation Phase.

Drug: Sirolimus

Escalation Phase: Sirolimus starting dose1 mg by mouth on Days 1 - 28.

Expansion Phase starting dose: MTD from Escalation Phase.

Other Name: Rapamune
Drug: Vorinostat

Arm A - Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.

Expansion Phase starting dose: MTD from Escalation Phase.

Arm B + Arm C - Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Experimental: Arm B: Vorinostat + Everolimus

Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Escalation Phase: Everolimus starting dose 5 mg by mouth on Days 1 - 28.

Expansion Phase: MTD from Escalation Phase.

Drug: Vorinostat

Arm A - Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.

Expansion Phase starting dose: MTD from Escalation Phase.

Arm B + Arm C - Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Drug: Everolimus

Escalation Phase: Everolimus starting dose 5 mg by mouth on Days 1 - 28.

Expansion Phase: MTD from Escalation Phase.

Other Names:
  • Afinitor
  • Zortress
  • RAD001
Experimental: Arm C: Vorinostat + Temsirolimus

Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Escalation Phase: Temsirolimus starting dose 12.5 mg by vein on Days 1, 8, 15, 22.

Expansion Phase: MTD from Escalation Phase.

Drug: Vorinostat

Arm A - Escalation Phase: Vorinostat starting dose 100 mg by mouth on Days 7 - 28 of Cycle 1; For all other cycles, dose of 100 mg Days 1-28.

Expansion Phase starting dose: MTD from Escalation Phase.

Arm B + Arm C - Escalation and Expansion Phase: Vorinostat dose 300 mg by mouth on Days 7 - 28. Rest of cycles: 300 mg by mouth on Days 1 - 28.

Other Names:
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
Drug: Temsirolimus

Escalation Phase: Temsirolimus starting dose 12.5 mg by vein on Days 1, 8, 15, 22.

Expansion Phase: MTD from Escalation Phase.

Other Names:
  • CCI-779
  • Torisel

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a histologically-confirmed metastatic or locally advanced cancer that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy that increases survival by at least three months does not exist
  2. There is no limit on the number of prior treatment regimens
  3. Patients must be off prior cytotoxic chemotherapy for at least three weeks. For biologic or targeted therapy, there should be five half lives or three weeks, whichever is shorter, between their last treatment and the first dose on this trial.
  4. Patients may receive palliative radiation therapy before or during treatment on protocol, provided that there is measurable or evaluable disease out of the radiation field. Patients may receive palliative radiation therapy, if needed, 48 hours after last dose of investigational drug. In addition patients may be enrolled on trial seven days following palliative radiation. We will closely monitor for the appearance of radiation recall reactions. Hormonal therapy may continue in patients who have been on such treatment for three months or longer.
  5. ECOG performance status 0-3
  6. Patients must have adequate organ and marrow function as defined by: absolute neutrophil count >/= 1000uL, platelets >/= 50,000uL, bilirubin </=2mg/dL in the absence of Gilbert's syndrome, ALT </= 2 x ULN or </=5x ULN if liver metastases present, creatinine </= 2mg/dL
  7. As the effect of sirolimus or everolimus or temsirolimus and vorinostat in combination on the developing human fetus is not known, women of child-bearing potential and men must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 3 months after completion
  8. Female patients with child-bearing potential must have a negative serum or urine pregnancy test within 7 days of study enrollment. Nursing mothers should discontinue nursing
  9. Ability to understand and the willingness to sign a written informed consent document
  10. Measurable or evaluable disease
  11. Patient must be able to swallow pills

Exclusion Criteria:

  1. Myocardial infarction within 3 months prior to starting treatment
  2. Concomitant use of phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital or St. Johns wort, cyclosporine, diltiazem, ketoconazole should be discontinued if possible. The list of CYP3A4 inhibitors: http://medicine.iupui.edu/clinpharm/ddis/clinical-table/
  3. Patient has a known hypersensitivity to the components of study drugs, its analogues, or drugs of similar chemical or biologic composition
  4. Patient is pregnant or breastfeeding
  5. Major surgical procedure within 28 days of day 1 of therapy
  6. Use of any other concurrent investigational agents or anticancer agents except for hormonal therapy as outlined in inclusion criteria
  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 ClinicalTrials.gov identifier: NCT01087554

Contacts
Contact: Filip Janku, MD, PHD 713-563-1930

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

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01087554     History of Changes
Other Study ID Numbers: 2009-0729, NCI-2011-00562
Study First Received: March 15, 2010
Last Updated: May 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancer
Sirolimus
Rapamune
mTOR Inhibitor
Histone Deacetylase Inhibitor
Vorinostat
SAHA
Suberoylanilide Hydroxamic Acid
MSK-390
Zolinza
Everolimus
Afinitor
Zortress
RAD001
Temsirolimus
CCI-779
Torisel

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

ClinicalTrials.gov processed this record on September 18, 2014