Doxil, Bevacizumab and Temsirolimus Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00761644
First received: September 25, 2008
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

The goal of this clinical research study is to learn the highest safe doses of the combination of Doxil (liposomal doxorubicin), Avastin (bevacizumab), and Torisel (Temsirolimus) that can be given to patients with advanced cancer that has spread or is unable to be surgically removed. The safety and effectiveness of this combination of drugs will also be studied.


Condition Intervention Phase
Advanced Cancer
Drug: Doxil
Drug: Bevacizumab
Drug: Temsirolimus
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Doxil, Bevacizumab and Temsirolimus

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated doses (MTDs) and Dose-limiting toxicities (DLTs) [ Time Frame: First cycle (21 days) ] [ Designated as safety issue: Yes ]
    MTD defined as dose level below dose at which 2 of 6 patients experience drug-related dose limiting toxicity (DLT) in first cycle. Dose limiting toxicity (DLT) defined as any grade 3 or 4 non-hematologic toxicity defined in the NCI CTC v3.0, even if expected and believed related to the study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by NCI-CTCAE), despite supportive care; any Grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other Grade 3 non-hematologic toxicity including 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 attributable to the therapy.


Estimated Enrollment: 206
Study Start Date: August 2008
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxil, Bevacizumab + Temsirolimus

Doxil day 1 of each 21 day cycle, beginning dose level 10 mg/m^2 by vein over 3 hours.

Bevacizumab day 1 of each 21 day cycle, beginning dose level 5 mg/kg by vein over 90 minutes.

Temsirolimus days 1, 8 & 15 of 21 Day Cycle, beginning dose level 12.5 mg by vein over 30 to 60 minutes.

Drug: Doxil
Day 1 of each 21 day cycle, beginning dose level 10 mg/m^2 by vein over 3 hours.
Other Names:
  • Liposomal doxorubicin
  • Doxorubicin hydrocholoride (lipsomal)
Drug: Bevacizumab
Day 1 of each 21 day cycle, beginning dose level 5 mg/kg by vein over 90 minutes.
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Temsirolimus
Days 1, 8 & 15 of 21 Day Cycle, beginning dose level 12.5 mg by vein over 30 to 60 minutes.
Other Names:
  • CCI-779
  • Torisel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or has no standard therapy that improves survival by at least three months.
  2. All patients must have an estimated life expectancy of at least 12 weeks.
  3. Patients must have measurable or evaluable disease
  4. Patients must have been off previous chemotherapy or radiotherapy for the three weeks prior to entering this study. Six weeks will be required if the patient has received therapy which is known to have delayed toxicity (mitomycin or a nitrosurea). Five half-lives will be required for biologic/targeted therapies with short (<24 hour) half-lives and pharmacodynamic effects. Patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available.
  5. ECOG performance status </= 2 (Karnofsky >/= 60%).
  6. Patients must have organ and marrow function defined as: absolute neutrophil count >/= 1,500/mL; platelets >/=100,000/mL; creatinine </= 3 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN. In patients with significant liver disease and chronically elevated liver transaminases, ALT may be elevated as high as 8 X ULN.
  7. Cardiac ejection fraction >/= 50% without evidence of CHF
  8. Women of child-bearing 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 90 days after the last dose.
  9. Ability to understand and the willingness to sign a written informed consent document.
  10. Patients may not be receiving any other investigational agents and/or any other concurrent anticancer agents or therapies except hormonal maintenance treatment for prostate cancer.

Exclusion Criteria:

  1. Patients with clinically significant unexplained bleeding within 28 days prior to entering the study
  2. Poorly controlled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg)
  3. Patients with clinically significant cardiovascular disease: - History of CVA within 6 months - Myocardial infarction or unstable angina within 6 months - Unstable angina pectoris - New York Heart Association Class CHF score ≥ II
  4. Prior cumulative doxorubicin dose > 300 mg/m2
  5. Pregnant or lactating women
  6. History of hypersensitivity to doxil, doxorubicin, HCL, temsirolimus or it's metabolites (including sirolimus), polysorbate 80, bevacizumab or murine products
  7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  8. Patients < 12 years of age
  9. Inability to swallow tablets for everolimus arm.
  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: NCT00761644

Contacts
Contact: Daniel Karp, MD 713-563-1930

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Daniel Karp, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00761644     History of Changes
Other Study ID Numbers: 2008-0384, NCI-2012-01665
Study First Received: September 25, 2008
Last Updated: September 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Metastatic cancer
Doxil
Liposomal doxorubicin
Doxorubicin hydrochloride (liposomal)
Avastin
Bevacizumab
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Torisel
Temsirolimus
CCI-779
Dynamic contrast-enhanced magnetic resonance imaging
DCE-MRI scan

Additional relevant MeSH terms:
Bevacizumab
Liposomal doxorubicin
Doxorubicin
Sirolimus
Antibodies, Monoclonal
Everolimus
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 01, 2014