Safety Study & Effectiveness of Docetaxel With RAD001 and Bevacizumab in Men With Advanced Prostate Cancer

NCT00574769 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 4P-09-4AVF3955sCRAD001CUS2468
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

Prostate cancer is a common and important health issue. Although effective treatment is often available for localized disease, metastatic prostate cancer remains incurable. The initial treatment for metastatic prostate cancer often includes medical or surgical treatments that deprive the tumor of male hormones (androgens) required for growth. Although this treatment is successful for many patients, the cancer may eventually return in others. Recurrent prostate cancer may be treated with additional hormonal agents, but these agents usually do not result in long-term control of the disease. Eventually most patients with recurrent prostate cancer progress to a state where the cancer grows despite very low level of circulating male hormones known as androgen independent prostate cancer (AIPC).

Conditions

Prostate Cancer

Keywords

RAD001; mTOR inhibition; docetaxel; bevacizumab; adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer; prostate cancer; Metastatic, androgen independent prostate cancer

Outcome Measures

Primary Outcomes (1)

• Establish a maximal tolerated or optimal biologic dose of RAD001 in combination with docetaxel/bevacizumab

  After the last patient in the cohort has completed at least two cycles of RAD001/docetaxel/bevacizumab

Secondary Outcomes (1)

• Evaluate the efficacy of RAD001 in combination with docetaxel/bevacizumab as determined by best overall response and progression-free survival in patients with advanced prostate cancer.

  overall survival

Study Arms (1)

1

EXPERIMENTAL

Drug: RAD001, Docetaxel, Bevacizumab

Interventions

RAD001, Docetaxel, Bevacizumab DRUG

RAD001 oral, 2.5 mg daily RAD001 oral, 5mg daily Bevacizumab infusion (IV), 15 mg/kg every 21 days Docetaxel infusion (IV), 75 mg/m\^2 every 21 days

Also known as: everolimus, Avastin, Taxotere

1

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Signed informed consent
• ECOG performance status: 0-2
• Histologically documented adenocarcinoma of the prostate
• Progressive disease despite androgen deprivation therapy. Progressive disease is defined as any one of the following:
• Measurable Disease: Objective evidence of increase \> 20% in the sum of the longest diameters of target lesions from the time of maximal regression or the appearance of one or more new lesions (Modified RECIST Criteria)
• Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer
• PSA Progression: An elevated PSA (≥ 5 ng/ml) which has risen serially from baseline on two occasions each at least one week apart
• At least 4 weeks since any other hormonal therapy. Flutamide and megestrol acetate (any dose) must be discontinued at least 4 weeks prior to initiating treatment. Bicalutamide or nilutamide must be discontinued at least 6 weeks prior to initiating treatment. If improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above. Androgen suppression should be continued
• ≥ 4 weeks since major surgery and fully recovered
• ≥ 8 weeks since high risk surgery and fully recovered
• ≥ 4 weeks since any prior radiation and fully recovered
• ≥ 6 weeks since the last dose of bone targeted radiopharmaceutical
• Men of child-bearing potential are required to use an effective means of contraception
• Required Initial Laboratory Values:

You may not qualify if:

• Prior treatment with cytotoxic chemotherapy for metastatic disease
• Prior treatment with anti-angiogenic agents, including thalidomide and bevacizumab
• Prior treatment with any investigational drug within 4 weeks of initiating treatment
• Prior treatment with an mTor inhibitor
• Chronic treatment with systemic steroids or another immunosuppressive agent
• Known history of HIV seropositivity
• Known brain metastases (brain imaging is not required)
• Congestive heart failure
• Uncontrolled hypertension. Patients with history of hypertension must be well controlled (\< 150/100) on a regimen of anti-hypertensive therapy
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• Active bleeding diathesis or on oral anti-vitamin K medications (except low dose coumarin)
• Arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), at any time
• History of unstable angina or angina requiring surgical or medical intervention in the past 12 months, or myocardial infarction (MI)

Sponsors & Collaborators

• University of Southern California: lead
• Novartis: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Westside Prostate Cancer Center, University of Southern California

Beverly Hills, California, 90211, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

Everolimus; Docetaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mitchell E Gross, MD, Ph.D

  University of Southern California

  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: December 14, 2007
• First Posted: December 17, 2007
• Study Start: February 17, 2010
• Primary Completion: February 17, 2016
• Study Completion: February 17, 2017
• Last Updated: April 11, 2017

Record last verified: 2017-04

Locations

US (2)