Doxil, Bevacizumab and Temsirolimus Trial

NCT00761644 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2008-0384NCI-2012-01665
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated doses (MTDs) and Dose-limiting toxicities (DLTs)

  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.

  First cycle (21 days)

Secondary Outcomes (2)

• Anti-Tumor Efficacy of Drug Combination

  4 months

• Anti-Tumor Efficacy of Drug Combination

  4 months

Study Arms (1)

Doxil, Bevacizumab + Temsirolimus

EXPERIMENTAL

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; Drug: Bevacizumab; Drug: Temsirolimus

Interventions

Doxil DRUG

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

Also known as: Liposomal doxorubicin, Doxorubicin hydrocholoride (liposomal)

Doxil, Bevacizumab + Temsirolimus

Bevacizumab DRUG

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

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Doxil, Bevacizumab + Temsirolimus

Temsirolimus DRUG

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

Also known as: CCI-779, Torisel

Doxil, Bevacizumab + Temsirolimus

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• All patients must have an estimated life expectancy of at least 12 weeks.
• Patients must have measurable or evaluable disease
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2 (Karnofsky \>/= 60%).
• Patients must have organ and marrow function defined as: absolute neutrophil count \>/= 1,500/mL; platelets \>/=100,000/mL; creatinine \</= 3 X upper limit of normal (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.
• Cardiac ejection fraction \>/= 50% without evidence of congestive heart failure (CHF).
• 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.
• Ability to understand and the willingness to sign a written informed consent document.
• 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.

You may not qualify if:

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

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

Neoplasm Metastasis

Interventions

liposomal doxorubicin; Liposomes; Bevacizumab; temsirolimus

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Membranes, Artificial; Biomedical and Dental Materials; Drug Carriers; Dosage Forms; Pharmaceutical Preparations; Manufactured Materials; Technology, Industry, and Agriculture; Biomimetic Materials; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daniel Karp, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 25, 2008
• First Posted: September 29, 2008
• Study Start: August 21, 2008
• Primary Completion: March 28, 2019
• Study Completion: March 28, 2019
• Last Updated: April 11, 2019

Record last verified: 2019-04

Locations

US (1)