RAD001 and Bicalutamide for Androgen Independent Prostate Cancer

NCT00630344 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 07-316
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

In the treatment of castration-resistant prostate cancer (CRPC), therapies will long response durations remain elusive as a result of the inherent ability of prostate cancer cells to develop iterative resistance. The goal of this study is to learn if the study drug RAD001 together with Bicalutamide can slow the growth of prostate cancer. The safety of the combination will also be studied.

Conditions

Prostate Cancer

Keywords

RAD001; bicalutamide; androgen independent prostate cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Overall response rate is the percentage of patients achieving response taking into consideration measurable disease, bone metastases, and PSA. PSA declines in the absence of both measurable disease and the appearance of new bone lesions or a response in measurable disease without an increase in PSA or the appearance of new bone lesions. Patients with stable disease (SD) lasting at least 6 months will also be considered responders. Per RECIST guidelines, for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation is required within 4 weeks. Per modified PSAWG2 criteria (Scher H, Halabi S, Tannock I et al. JCO 2008) PSA response is defined as PSA decline ≥ 50% from baseline confirmed by a second measurement at least 4 weeks later.

  PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.

Secondary Outcomes (5)

• Incidence of Grade 4 Treatment-Related Toxicity

  Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

• Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity

  Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

• Incidence of Grade 1-3 Treatment-Related Rash Toxicity

  Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

• Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity

  Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.

• Time to Progression (TTP)

  PSA was measured monthly and measurable disease on imaging assessed every 2 cycles in first 8 weeks and every 3 cycles thereafter. In this study cohort, patients were followed on treatment up to approximately 1 year.

Study Arms (1)

RAD001 + Bicalutamide

EXPERIMENTAL

RAD001: once daily dose of 10 mg (5 mg tablets) Bicalutamide: once daily dose of 50 mg (50 mg tablets) 1 cycle=28 days Both agents are administered continuously until progression of disease or unacceptable toxicity.

Drug: RAD001; Drug: Bicalutamide

Interventions

RAD001 DRUG

Also known as: everolimus

RAD001 + Bicalutamide

Bicalutamide DRUG

Also known as: Casodex

RAD001 + Bicalutamide

Eligibility Criteria

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

You may qualify if:

• years of age or older
• Histologically documented prostate cancer
• Castration resistant prostate cancer defined as two rising PSAs on castration therapy
• Baseline PSA of 2ns/mL or greater
• Testosterone of 50ng/mL or less
• Patients on LHRH agonist/antagonist must continue therapy at the recommended dosing intervals
• Prior bicalutamide is allowed as long as treatment was for 6 months or longer
• Metastatic disease is not required
• Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy
• ECOG Performance Status equal to or less than 2
• Adequate bone marrow and liver function as outlined by parameters in the protocol

You may not qualify if:

• Prior treatment with any investigational drug within the preceding 4 weeks
• Prior treatment with an mTOR inhibitor
• Fasting lipids over the parameters outlined in the protocol
• Chronic treatment with systemic steroids or another immunosuppressive agent
• Patients should not receive immunization with attenuated live vaccines during study period or within one week of study entry
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated or basal squamous cell carcinomas of the skin
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin)
• Men able to conceive and unwilling to practice an effective method of birth control
• Known hypersensitivity to RAD001 or other rapamycins or to its excipients
• History of noncompliance to medical regimens

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Beth Israel Deaconess Medical Center: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Nakabayashi M, Werner L, Courtney KD, Buckle G, Oh WK, Bubley GJ, Hayes JH, Weckstein D, Elfiky A, Sims DM, Kantoff PW, Taplin ME. Phase II trial of RAD001 and bicalutamide for castration-resistant prostate cancer. BJU Int. 2012 Dec;110(11):1729-35. doi: 10.1111/j.1464-410X.2012.11456.x. Epub 2012 Aug 29.

  PMID: 22928480 RESULT

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Everolimus; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Mary-Ellen Taplin, MD
• Organization: Dana-Farber Cancer Institute

mary_taplin@dfci.harvard.edu

617-582-8313

Study Officials

• Mary-Ellen Taplin, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 28, 2008
• First Posted: March 7, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: December 8, 2017
• Results First Posted: March 3, 2014

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)