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RAD001 and Bicalutamide for Androgen Independent Prostate Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00630344
First Posted: March 7, 2008
Last Update Posted: December 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Beth Israel Deaconess Medical Center
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
February 28, 2008
March 7, 2008
January 20, 2014
March 3, 2014
December 8, 2017
February 2008
May 2012   (Final data collection date for primary outcome measure)
Overall Response Rate [ Time Frame: 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. ]

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.

To Determine the Best Overall Response and Duration of Response, Taking Into Consideration Measurable Disease, Bone Metastases and PSA. [ Time Frame: 3 years ]
Complete list of historical versions of study NCT00630344 on ClinicalTrials.gov Archive Site
  • Incidence of Grade 4 Treatment-Related Toxicity [ Time Frame: Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort. ]
    All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation.
  • Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity [ Time Frame: Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort. ]
    All grade 1-3 mucositis adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 mucositis AE during the time of observation.
  • Incidence of Grade 1-3 Treatment-Related Rash Toxicity [ Time Frame: Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort. ]
    All grade 1-3 rash adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 rash AE during the time of observation.
  • Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity [ Time Frame: Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort. ]
    All grade 1-3 fatigue adverse events (AE) with treatment attribution of possible, probable or definite based on CTCAEv3 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 1-3 fatigue AE during the time of observation.
  • Time to Progression (TTP) [ Time Frame: 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. ]
    TTP estimated with Kaplan-Meier methods is defined as the time from treatment start to when PSA progression criteria is first met, or the date of measurable or non-measurable disease progression (PD). Absent progression, patients are censored at the date of the last PSA measurement. PSA progression is a ≥25% increase over baseline or nadir PSA, whichever is lowest with a minimum increase of 5 ng/mL. If PSA declines ≥50%, PSA progression is a ≥50% PSA increase above nadir with a minimum increase of 5 ng/mL or back to pretreatment baseline, whichever is lowest. PSA progression requires 2 week confirmation. Per RECIST, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. Non-measurable PD is defined as a worsening bone scan, as indicated by the appearance of two or more new lesions, the appearance of new non-bony metastases or a requirement for radiation therapy.
To Characterize the Toxicity Profile of RAD001 in Combination With Standard Dose Bicalutamide in Patients With Androgen Independent Prostate Cancer. [ Time Frame: 3 years ]
Not Provided
Not Provided
 
RAD001 and Bicalutamide for Androgen Independent Prostate Cancer
A Phase II Trial of RAD001 and Bicalutamide for Androgen Independent Prostate Cancer
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.

Bicalutamide, an androgen receptor (AR) antagonist, is frequently used as the first 'secondary hormonal therapy' in combination with another established agent (LHRH: luteinizing hormone-releasing hormone agonist/antagonist) to treat CRPC. A series of studies have shown that RAD001 through inhibition of mammalian target of rapamycin (mTOR) pathway has antitumor and anti-angiogenic activities. The hypothesis is that the combination of an antiandrogen and mTOR inhibitor would have additive and clinically significant effects in CRPC.

STATISTICAL CONSIDERATIONS:

The regimen will be considered promising if the rate of response/favorable outcome is 40% or greater. A rate of 20% (similar to that observed for bicalutamide alone) will not be considered worthy of further study. 38 patients (of whom 36 are assumed to be eligible) will be accrued to the study. If 11 or more patients have a favorable outcome (stable disease > 6 months or response), the combination will be considered worthy of further study. Given this design, there is a 9% probability of declaring the combination effective if the true favorable outcome rate is 20% and a 91% probability of declaring the combination effective if the true favorable outcome rate is 40%.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Prostate Cancer
  • Drug: RAD001
    Other Name: everolimus
  • Drug: Bicalutamide
    Other Name: Casodex
Experimental: RAD001 + Bicalutamide

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.

Interventions:
  • Drug: RAD001
  • Drug: Bicalutamide
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
May 2012
May 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18 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

Exclusion Criteria:

  • 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
Sexes Eligible for Study: Male
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00630344
07-316
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
  • Beth Israel Deaconess Medical Center
  • Novartis Pharmaceuticals
Study Chair: Mary-Ellen Taplin, MD Dana-Farber Cancer Institute
Dana-Farber Cancer Institute
November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP