Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Androgens

Everolimus

Bicalutamide

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Androgen Antagonists

Hormones

Hormone Antagonists

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.

RAD001

Mary-Ellen Taplin, MD

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%.

RAD001 and Bicalutamide for Androgen Independent Prostate Cancer

A Phase II Trial of RAD001 and Bicalutamide for Androgen Independent Prostate Cancer

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.

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.

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.

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.

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.

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.

Beth Israel Deaconess Medical Center

Novartis Pharmaceuticals

Dana-Farber Cancer Institute

Principal Investigator

RAD-001+ Bicalutamide

RAD-001 in Combination With Bicalutamide

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

RAD-001 + Bicalutamide

The analysis dataset is comprised of all treated patients.

Overall Response Rate

RAD001 + Bicalutamide

Incidence of Grade 4 Treatment-Related Toxicity

Incidence of Grade 1-3 Treatment-Related Mucositis Toxicity

Incidence of Grade 1-3 Treatment-Related Rash Toxicity

Incidence of Grade 1-3 Treatment-Related Fatigue Toxicity

Time to Progression (TTP)

Overall Study

Symptoms and General Pathology

Adenocarcinoma

Neoplasm Metastasis

Bone Density Conservation Agents

Zoledronic Acid

Atrasentan

Endothelin A Receptor Antagonists

Endothelin Receptor Antagonists

Zoledronic Acid (Zometa)

Matthew Smith, MD, PhD

The main purpose of this study is to look at the effects (good or bad) that Atrasentan given alone and Atrasentan given with Zometa has on levels of bone formation and bone destruction in men with prostate cancer that has spread to the bones.

* Patients will be randomized to either receive Atrasentan alone or Atrasentan plus Zometa.
* Patients receiving Atrasentan alone will receive this drug in pill form once daily for 12 weeks. Patients will have a physical exam, blood work, and a urine sample performed once every other week during the first four weeks of medication administration. After those two initial visits, they will return to the clinic once every 4 weeks to have the same tests repeated. A bone scan and abdominal-pelvic CT Scan will be done every 12 weeks.
* After the patient has been taking Atrasentan for 12 weeks, if the disease has not progressed, they will begin combination treatment of Atrasentan and Zometa.
* Patients receiving Atrasentan plus Zometa, receive Zometa intravenously and then immediately start Atrasentan orally once daily as long as they remain on the study. Patients will return to the clinic twice over the first 4 weeks (once every other week) to have a physical exam, blood work and urine test performed. After these two initial visits, they will return to the clinic once every 4 weeks to have the tests repeated and to receive another treatment of zometa. A bone scan and an abdominal-pelvic CT Scan will be done once every 12 weeks.
* Patients participation in this study will last as long as the disease does not progress and they are not experiencing any serious side effects.

Atrasentan and Zometa for Men With Prostate Cancer Metastatic to Bone

Atrasentan and Zometa for Men With Androgen Independent Prostate Cancer Metastatic to Bone: A Randomized Pilot Study

Brigham and Women's Hospital

Abbott

Massachusetts General Hospital

Matthew R. Smith, MD, PhD

Micronutrients

Vasoconstrictor Agents

Docetaxel

Calcitriol

Tubulin Modulators

Antimitotic Agents

Calcium

Calcium, Dietary

Vitamins

Trace Elements

calcitriol

docetaxel

Tomasz Beer, MD

The purposes of this study are to determine if DN-101 plus Taxotere lowers PSA levels, delays or limits disease progression and is safe with minimal side effects.

DN-101 is an investigational drug that has not been approved by the U.S. Food and Drug Administration (FDA). It is a newly formulated pill that contains high amounts of calcitriol, a naturally occurring hormone and the biologically active form of vitamin D. Administration of DN-101 results in much higher blood levels of calcitriol than the body can produce from dietary vitamin D or vitamin D supplements. These higher levels of calcitriol are associated with anti-cancer effects in laboratory models of human cancer. Laboratory models also indicate that calcitriol has synergy with many commonly used chemotherapeutic agents used to treat cancer.

Calcitriol, at very low doses, is currently approved for use in patients with chronic kidney failure. DN-101 was specifically designed for cancer and contains 30 times the amount of calcitriol found in the calcitriol pill commercially available today. In order to take an amount of calcitriol equivalent to 1 DN-101 pill, cancer patients would need to swallow 30 pills of the approved, low dose formulation. DN-101 represents a breakthrough in the use of calcitriol in the clinic, because it contains high concentrations of calcitriol and makes it more feasible for patients to stay on regimen.

ASCENT: Androgen Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere

A Phase 2/3 Multicenter, Randomized, Double Blind Study of Docetaxel (Taxotere) Plus DN-101 or Placebo in Androgen Independent Prostate Cancer (AIPC)

Aventis Pharmaceuticals

Novacea

Taxane

This was a single arm open-label study. All patients enrolled received 20 mg of IRX4204 per day orally, for six months, or longer if the patient had disease stabilization and was tolerating the experimental treatment.

NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day

NRX 194204

Lalita Pandit, MD

This study is to evaluate the benefits of investigational drug, NRX 194204 in slowing down/stopping/reversing progression of the castration resistant and taxane resistant prostate cancer.

Numerous studies in pre-clinical models and in human clinical trials have clearly established the potential for the use of rexinoids in the treatment and prevention of cancer. NRX 194204, a second generation rexinoid, is a highly potent and specific activator of RXRs (retinoid X receptors). Because NRX 194204 is significantly more selective for the RXRs relative to the RARs (retinoic acid receptors) than a first generation approved drug, it is associated with fewer adverse events in clinical use. This study seeks to investigate NRX 194204 monotherapy in patients with castration- and taxane- resistant prostate cancer.

Trial of NRX 194204 in Castration- and Taxane-Resistant Prostate Cancer

A Phase II Trial of NRX 194204 in Castration- and Taxane-Resistant Prostate Cancer

Clinical benefit will be defined as either non-progression at 8 weeks or radiologic and/or PSA response at any time point with no dose limiting toxicity (DLT) or other toxicity requiring termination of treatment.

Overall Survival \[Time Frame: participants will be followed for the duration of treatment and follow up, which is up to 2.5 years\]

Time to Disease Progression was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. Progression was defined as at least a 20% relative increase and an absolute increase of at least 5mm; or appearance of new lesions.

Number of Grade 3 and higher Adverse Events deemed at least possibly related to NRX 194204

Prostate specific Antigen (PSA) response rate based on 50% reduction from baseline PSA

Io Therapeutics

This was a single arm open-label study. All patients enrolled received 20 mg of IRX4204 per day orally, for six months, or longer if the patient had disease stabilization and was tolerating the experimental treatment.

NRX 194204: NRX 194204 is an oblong, soft, gelatin capsule and will be taken once a day

Ethnicity (NIH/OMB)

Martin E. Sanders, M.D.

Clinical Benefit of NRX 194204 in Men With Castration- and Taxane-resistant Metastatic Prostate Cancer

This was a single arm open-label study. All patients enrolled and treated received 20 mg of IRX4204 per day orally, for six months, or longer if the patient had disease stabilization and was tolerating the experimental treatment.

Overall Survival

Time to Disease Progression

Number of Grade 3 and Higher Adverse Events Deemed at Least Possibly Related to NRX 194204

partial response

stable disease

progressive disease

PSA Response Rate

NRX 194204 capsules, 20 mg PO once per day

Rare Diseases

Kennedy Disease

Reproductive Control Agents

Mifepristone

Contraceptive Agents

Contraceptives, Oral

Contraceptive Agents, Female

Contraceptives, Postcoital

Contraceptive Agents, Hormonal

The purpose of this study is to determine the effects (good and bad) that mifepristone has on patients with androgen independent prostate cancer.

Patients will receive mifepristone, 200mg orally once a day. One treatment cycle is 28 days long. Patients will remain on treatment unless their cancer gets worse or they develop intolerable side effects.

At the end of each cycle a physical examination, routine blood tests, and hormone levels will be performed.

After every 3 cycles, one or more of the following will be performed: bone scan, chest x-ray, CT scan or MRI.

Mifepristone (RU-486) in Androgen Independent Prostate Cancer

A Phase II Study of Mifepristone (RU-486) in Androgen Independent Prostate Cancer With Correlative Assessment of Androgen Receptor Co-Repressor Proteins

Georgetown University

Mary-Ellen Taplin

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
RAD001 and Bicalutamide for Androgen Independent Prostate Cancer	NCT00630344	Prostate Cancer	RAD001 Bicalutamide	18 Years -	Dana-Farber Cancer Institute
Atrasentan and Zometa for Men With Prostate Cancer Metastatic to Bone	NCT00181558	Prostate Cancer Adenocarcinoma ...	Atrasentan Zoledronic Acid...	18 Years -	Massachusetts General Hospital
RAD001 and Bicalutamide for Androgen Independent Prostate Cancer	NCT00630344	Prostate Cancer	RAD001 Bicalutamide	18 Years -	Dana-Farber Cancer Institute
ASCENT: Androgen Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere	NCT00043576	Prostate Cancer	calcitriol docetaxel	18 Years -	Novacea
Trial of NRX 194204 in Castration- and Taxane-Resistant Prostate Cancer	NCT01540071	Castration Resi...	NRX 194204	18 Years -	Io Therapeutics
Mifepristone (RU-486) in Androgen Independent Prostate Cancer	NCT00140478	Prostate Cancer Adenocarcinoma ...	Mifepristone	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for androgen independent prostate cancer