A Phase 2 interventional study of RAD001 and Bicalutamide in Prostate Cancer, sponsored by Dana-Farber Cancer Institute. Completed at 2 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-12-08.
Sponsored by Dana-Farber Cancer Institute · Phase 2, Interventional, and Treatment
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%.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 36 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.
Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.
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Exclusion Criteria:
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
Also known as: everolimus
Also known as: Casodex
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.
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.
Incidence of Grade 4 Treatment-Related Toxicity
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.
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.
Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity
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.
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.
Incidence of Grade 1-3 Treatment-Related Rash Toxicity
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.
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.
Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity
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 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.
Time to Progression (TTP)
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.
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.
| Milestone | RAD001 + Bicalutamide |
|---|---|
| Started | 36 |
| Completed | 0 |
| Not completed | 36 |
| Withdrew: Adverse event | 5 |
| Withdrew: Progressive disease | 19 |
| Withdrew: Physician decision | 9 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Intercurrent illness | 1 |
| Withdrew: Other | 1 |
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.
| percentage of patients | RAD-001 + Bicalutamide |
|---|---|
| Overall Response Rate | 6 (1 to 16) |
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.
| Participants | RAD001 + Bicalutamide |
|---|---|
| Incidence of Grade 4 Treatment-Related Toxicity | 0 |
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.
| Participants | RAD001 + Bicalutamide |
|---|---|
| Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity | 20 |
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.
| Participants | RAD001 + Bicalutamide |
|---|---|
| Incidence of Grade 1-3 Treatment-Related Rash Toxicity | 17 |
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.
| Participants | RAD001 + Bicalutamide |
|---|---|
| Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity | 16 |
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.
| weeks | RAD001 + Bicalutamide |
|---|---|
| Time to Progression (TTP) | 8.7 (0 to 43.6) |
Collected over Assessed each cycle during therapy and up to 30 days post-therapy completion which is approximately 1 year for patients in this study cohort.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| RAD-001+ Bicalutamide | — | 19/36 (52.8%) | 35/36 (97.2%) |
| Event | RAD-001+ Bicalutamide |
|---|---|
| HyperglycemiaMetabolism and nutrition disorders | 3/36 |
| HemoglobinBlood and lymphatic system disorders | 2/36 |
| FatigueGeneral disorders | 2/36 |
| HyponatremiaMetabolism and nutrition disorders | 2/36 |
| Double visionEye disorders | 1/36 |
| Muco/stomatitis by exam- oral cavityGastrointestinal disorders | 1/36 |
| Pain-otherGeneral disorders | 1/36 |
| Infection neut-anal/perianlInfections and infestations | 1/36 |
| LeukocytesInvestigations | 1/36 |
| Alkaline phosphataseInvestigations | 1/36 |
| Event | RAD-001+ Bicalutamide |
|---|---|
| FatigueGeneral disorders | 14/36 |
| Rash/desquamationSkin and subcutaneous tissue disorders | 10/36 |
| Muco/stomatitis by exam- oral cavityGastrointestinal disorders | 10/36 |
| Diarrhea w/o prior colostomyGastrointestinal disorders | 9/36 |
| Muco/stomatitis (symptom) oral cavityGastrointestinal disorders | 9/36 |
| AnorexiaMetabolism and nutrition disorders | 7/36 |
| NauseaGastrointestinal disorders | 7/36 |
| Back- painMusculoskeletal and connective tissue disorders | 7/36 |
| CoughRespiratory, thoracic and mediastinal disorders | 7/36 |
| Rash: acne/acneiformSkin and subcutaneous tissue disorders | 6/36 |
| Age, Categorical(Participants) | RAD-001 in Combination With Bicalutamide |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 13 |
| >=65 years | 23 |
| Age, Continuous(years) | RAD-001 in Combination With Bicalutamide |
|---|---|
| Median | 68 (60 to 72) |
| Sex: Female, Male(Participants) | RAD-001 in Combination With Bicalutamide |
|---|---|
| Female | 0 |
| Male | 36 |
| Region of Enrollment(Participants) | RAD-001 in Combination With Bicalutamide |
|---|---|
| United States | 36 |
Plan to share: No
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