Clinical Trials


Clinical trials, also called clinical studies, test new methods to treat, diagnose and prevent cancer. Only treatments that provide promising results in laboratory tests advance to clinical trials.

 

CLINICAL TRIALS

 

PHASE 3 TRIALS: Phase 3 clinical trials build upon evidence of effectiveness in previous phase 1 & 2 trials in small samples, and expand to a larger sample in an attempt to confirm the experimental treatment's efficacy. This also applies to investigation of an existing treatment (or treatment combination) not previously examined in a particular category of disease. Treatments investigated in Phase 3 trials have stronger evidence of effectiveness than in previous phases.

Phase 2 TRIALS: Build upon evidence of safety from previous phase 1 trials that indicate the relative safety and appropriate dosing of a new agent.  Once the phase 1 trial demonstrates the appropriate dosage, the phase 2 trial can commence to study the new agent in a single type of cancer to determine the response rate of the new agent.  So the advantage to the patient for a phase 2 trial is that 100% of the men involved in the trial get the new agent.  No placebos are involved.  The disadvantage is that the effectiveness of the new agent is still being tested so it is often impossible to know what the response rate will be for any specific patient contemplating embarking on a phase 2 trial.

Phase 1 TRIALS: Are performed primarily to determine the safe dosage of a brand new agent that has never been administered to humans before. Phase 1 trials start at a small dose and with successive patients who are accrued to the trial, the dosage is slowly escalated.  The trial ends when men start encountering unacceptable toxicity. Phase 1 trials are only for men who are very desperate or for the rare situation when clear cut responses have been reported with the men previously treated at lower doses with the same agent. 


PHASE III TRIALS


XOFIGO WITH ZYTIGA 

Radium-223 (Xofigo) and Abiraterone (Zytiga) Compared to Placebo and Abiraterone for Men With Cancer of the Prostate With Castration-Resistant, Metastatic Disease that Has Not Been Treated With Chemotherapy and is Causing no or Only Mild Symptoms (ERA 223). For more information visit: https://clinicaltrials.gov/show/NCT02043678

This trial is designed to test the premise that it is advantages to start Xofigo at an earlier stage rather than waiting until men become resistant to Zytiga. It is likely to benefit the patients who go on the trial because most people believe that earlier use of Xofigo will be advantageous.  Since many insurance companies will not pay for Xofigo unless bone pain is present, this is a good way for patients to get earlier access to an effective agent like Xofigo free of charge. 

Experimental agent: radium-223 (XOFIGO) may limit metastatic progression by targeting and killing bone cancer cells.
Purpose: Evaluate the effectiveness of radium-223 when combined with abiraterone, in terms of survival time without progression in skeletal disease.
Arm A: radium-223 + abiraterone (ZYTIGA)
Arm B: placebo + abiraterone
Notable eligibility criteria:
- Castrate-resistant metastatic disease
- Bone metastases only
- No bone pain requiring opioids/narcotics
- No prior chemotherapy

 

XTANDI COMPARED TO OLDER PILLS SUCH AS CASODEX AND FLUTAMIDE

Enzalutamide (Xtandi) in First Line Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer. For more information, visit: https://clinicaltrials.gov/show/NCT02446405

This phase 3 trial is testing the premise that earlier use of a more potent agent (Xtandi) will translate into improved survival.  Presently, for insurance reasons, access to Xtandi prior to the onset of hormone resistance is limited. Many experts believe, however, that early use of the most effective agent translates into improved survival.  This trial can benefit patients who have no potential access to the early use of Xtandi as it gives the participants a 50% chance they will receive the Xtandi free of charge.  

Experimental agent: enzalutamide (XTANDI) may reduce tumor cell growth by blocking androgen receptors.
Purpose: Compare overall survival time between enzalutamide and other anti-androgens.
Arm A: enzalutamide + LHRH analogue (e.g. LUPRON)
Arm B: Non-steroidal anti-androgen (e.g. nilutamide, bicalutamide flutamide) + LHRH Analogue
Notable eligibility criteria:
- Metastatic disease
- No prior chemotherapy - exception: up to 2 cycles of docetaxel for metastatic disease
- No history of seizure or conditions that predispose to seizure
- No history of Transient Isquemic Attacks

 

XTANDI WITH ZYTIGA

Enzalutamide (Xtandi) With or Without Abiraterone (Zytiga) and Prednisone in Treating Patients With Castration-Resistant Metastatic Prostate Cancer. For more information, visit: https://clinicaltrials.gov/show/NCT01949337

Xtandi and Zytiga block testosterone activity within the cancer cell using distinctly different biochemical pathways.  As such, both agents in combination are likely to be more effective than either agent by itself.  However, relatively few insurance companies will pay for the use of both of these agents at the same time.  Half the men in this study will receive a combination of both agents with the cost being borne by the company sponsoring the trial. 

Experimental agent: enzalutamide (XTANDI) may reduce tumor cell growth by blocking androgen receptors.
abiraterone (ZYTIGA) may suppress testosterone production by inhibiting activity of the CYP17 enzyme.
Purpose: Evaluate overall survival time under enzalutamide when combined with abiraterone.
Arm A: enzalutamide
Arm B: enzalutamide + abiraterone
Notable eligibility criteria:
- Castrate-resistant metastatic disease
- No prior abiraterone, enzalutamide, or any chemotherapy
- No history of seizure or related conditions
- No history of TIA within 12 months

 

DENDRITIC CELL VACCINE

Phase III Study of DCVAC Added to Standard Chemotherapy for Men with Metastatic Castration Resistant Prostate Cancer (VIABLE). For more information, visit: https://clinicaltrials.gov/show/NCT02111577

Immune therapy is becoming more mainstream in prostate cancer, lung cancer and melanoma.  Generally the side effects are quite minimal compared to other types of therapy.  This trial adds immune therapy to standard Taxotere chemotherapy to determine if the immune treatment improves response rates and survival.  Since this form of immune therapy is not yet FDA approved this trial is the only way for patients to access the drug.  

Experimental agent: dendritic cell vaccine (DCVAC/PCa) may destroy tumor cells by stimulating a cytotoxic T-lymphocyte (CTL) response against PSA-expressing cancer cells.
Purpose: Evaluate overall survival time under dendritic cell vaccine when combined with docetaxel.
Arm A: dendritic cells vaccine + docetaxel (TAXOTERE)
Arm B: placebo + docetaxel
Notable eligibility criteria:
- Castrate-resistant metastatic disease
- No prior chemotherapy
- No prior immunotherapy within 6 months

 

ARN-509

A Study of ARN-509 in Men With Non-Metastatic Castration-Resistant Prostate Cancer (SPARTAN). For more information, visit: https://clinicaltrials.gov/show/NCT01946204

ARN-509 is a pill with similar function to Xtandi that is being studied in men with hormone resistance who have yet to develop any metastases.  Xtandi is only approved for men with metastases so insurance coverage is often denied. The advantage for patients in this trial is the earlier exposure to a more potent agent at a time before the disease has progressed to overt metastases. 

Experimental agent: ARN-509, an androgen receptor antagonist, may inhibit tumor cell growth by inhibiting genes that regulate cancer cell proliferation.
Purpose: Assess the effectiveness (survival time without metastases) of ARN-509.
Arm A: ARN-509
Arm B: placebo
- Castrate-resistant disease WITHOUT metastases
- No prior abiraterone or enzalutamide
- No prior CYP17 inhibitors
- No prior chemotherapy

 

ARN-509

An Efficacy and Safety Study of JNJ56021927 in Participants With Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer (mCRPC). For more information, visit: https://clinicaltrials.gov/show/NCT02257736

This study compares Zytiga alone with Zytiga plus ARN-509. Zytiga and ARN-509 block testosterone activity within the cancer cell using distinctly different biochemical pathways.  As such, both agents in combination are likely to be more effective than either agent by itself.  However, patients outside of this trial have no possibly opportunity of being treated with ARN-509 and Zytiga simultaneously because RN-509 has not yet been approved by the FDA. Half the men in this study will receive a combination of both agents with the cost being borne by the company sponsoring the trial

Experimental agent: JNJ56021927 (ARN-509), an androgen receptor antagonist, may inhibit tumor cell growth by inhibiting genes that regulate cancer cell proliferation.
Purpose: Assess the effectiveness (survival time without disease progression on scans) of JNJ56021927 when combined with abiraterone.
Arm A: JNJ56021927 + abiraterone (ZYTIGA)
Arm B: placebo + abiraterone
Notable eligibility criteria:
- Castrate-resistant metastatic disease
- No prior chemotherapy (except adjuvant/neoadjuvant use)
- No pain requiring opioids/narcotics

 

ORTERONEL (TAK-700)

Phase III Lupron+TAK-700 vs. Lupron+Bicalutamide for Metastatic, Hormone-Sensitive Prostate Cancer (SWOG 1216)
For more information, visit: https://clinicaltrials.gov/show/NCT01809691

Bicalutamide (Casodex) is generally the standard first step when Lupron stops working.  However, bicalutamide is a relatively weak agent. TAK-700 is more potent than bicalutamide and is therefore likely to be more advantageous.  TAK-700 is not yet approved by the FDA and is only available via a clinical trial such as this. 

Experimental agent: orteronel (TAK-700) may suppress androgen-dependent tumor cell growth by inhibiting the 17,20 lyase steroid in the testes and adrenal glands.
Purpose: Compare overall survival time between TAK-700 (experimental) and bicalutamide (established).
Arm A: ADT (equivalent of LUPRON) + TAK-700
Arm B: ADT + bicalutamide (CASODEX)
- Metastatic disease
- No prior chemotherapy (neoadjuvant/adjuvant use allowed if > 2 years prior)
- No prior androgen deprivation therapy within 6 months (adjuvant/neoadjuvant use OK if total treatment < 36 months)
- No prior ketoconazole, aminoglutethimide, abiraterone, or enzalutamide

 

XTANDI

Safety and Efficacy Study of Enzalutamide in Patients With Nonmetastatic Castration-Resistant Prostate Cancer (PROSPER)
For more information, visit: https://clinicaltrials.gov/show/NCT02003924

Xtandi is FDA approved for men with hormone resistance who have already developed metastases.  However, insurance coverage is often denied for men with hormone resistance who are yet to develop metastases.  The advantage for patients in this trial is the earlier exposure to a potent agent like Xtandi at a time before the disease has progressed to overt metastases may be advantageous.

Experimental agent: enzalutamide (XTANDI) may reduce tumor cell growth by blocking androgen receptors.
Purpose: Assess the effectiveness (survival time without metastatic progression) of enzalutamide in nonmetastatic disease.
Arm A: enzalutamide
Arm B: placebo
- Castrate-resistant disease WITHOUT metastases
- PSA doubling time ≤ 10 months
- No prior hormonal therapy except for LHRH therapies (e.g. LURPON, ELIGARD)
- No prior chemotherapy


HORMONE SENSITIVE, LOCALIZED NON METASTATIC DISEASE


 

PROSTATAK

Phase 3 Study of ProstAtak™ Immunotherapy With Standard Radiation Therapy for Localized Prostate Cancer (PrTK03)
Immune therapy it believed to have greater anticancer activity when used to treat earlier, low-volume disease.  In this study men with newly-diagnosed cancer that is relatively high risk can undergo radiation with our without immunotherapy.  The hope is that the men who receive immunotherapy can benefit with improved cure rates. For more information, visit: https://clinicaltrials.gov/show/NCT01436968

Experimental agent: ProstAtak (AdV-tk) may stimulate an antitumor cytotoxic T lymphocyte (CTL) response by working in conjunction with valacyclovir to kill tumor cells overexpressing the HSV-tk gene.
Purpose: Assess the effectiveness (survival time without disease recurrence) of combining ProsAtak, valacyclovir, and radiation therapy with optional androgen deprivation therapy.
Enrollment: 711
Arm A: ProstAtak (AdV-tk) + valacyclovir + radiation therapy + (optional) androgen deprivation therapy
Arm B: placebo + valacyclovir + radiation therapy + (optional) ADT
Notable eligibility criteria:
- Intermediate Risk disease (PSA 10-20 ng/ml, Gleason score 7, T2b-T2c)
- No more than 1 High Risk feature (PSA>20 ng/ml, Gleason score 8-10, or T3a), no metastatic disease
- No prior treatment except TURP or ADT (maximum 6 months)

 

XTANDI

LHRH Analogue Therapy With Enzalutamide (Xtandi) or Bicalutamide (Casodex) in Treating Patients With Metastatic Hormone Sensitive Prostate Cancer.  For more information, visit: https://clinicaltrials.gov/show/NCT02058706

Until the relatively recent FDA approval of Xtandi for hormone resistant disease Casodex and Lupron was the only alternative.  This trial is designed to test the premise that initiating Xtandi immediately, rather than waiting for resistance to Casodex and Lupron develop, is advantageous for patients.  In this trial half the men will receive immediate Xtandi and the other half will receive the traditional combination of Casodex and Lupron. 

Agent: enzalutamide (XTANDI) may reduce tumor cell growth by blocking androgen receptors.
Purpose: Compare the effectiveness (PSA remission) between enzalutamide (experimental) and bicalutamide (known) in hormone sensitive prostate cancer.
Enrollment: 92
Arm A: enzalutamide + LHRH analogue (LUPRON, etc.)
Arm B: bicalutamide (CASODEX) + LHRH analogue
Notable eligibility criteria:
- Metastatic disease
- PSA ≥ 4 ng/ml within 28 days if no prior hormone therapy
- No prior neoadjuvant/adjuvant hormone therapy within 6 months
- No prior chemotherapy or androgen synthesis/receptor blockers (abiraterone, enzalutamide, TAK-700, ARN-509, etc.)
- No history of seizure or conditions that predispose to seizure. 


PROVENGE WITH YERVOY

A Randomized Phase 2 Trial of Combining Sipuleucel-T  With Immediate vs. Delayed CTLA-4 Blockade for Prostate Cancer
Immune therapy has been the hot topic of 2015 with new and powerful agents showing dramatic activity in both lung cancer and melanoma.  One agent, Yervoy, that works by “taking the brakes off the immune system” has affected notable responses in very difficult cases of melanoma.  Yervoy has also been tested in very advanced prostate cancer and shown to have notable activity.  Combining Yervoy with Provenge, another immunotherapy that is already FDA approved for prostate cancer is a very compelling concept. Despite the fact that Yervoy can be associated with potentially severe side effects, this Phase 2 trial is potentially one of the most attractive trials for patient with hormone resistant disease. For more information, visit: https://clinicaltrials.gov/show/NCT01804465

Experimental agent: sipuleucel-T (PROVENGE) may stimulate an antitumor T-cell response against PAP-expressing tumor cells. Ipilimumab (YERVOY) may stimulate a cytotoxic T-lymphycite (CTL)-mediated immune response against cancer cells by inhibiting the CTLA4-mediated downregulation of T-cell activation.
Purpose: Assess the impact (on immune response) of the timing of ipilimumab following sipuleucel-T.
Arm A: sipuleucel-T + immediate ipilimumab
Arm B: sipuleucel-T + 3-week delayed ipilimumab
Notable eligibility criteria:
- Castrate-resistant metastatic disease
- No prior chemotherapy except neoadjuvant use
- No prior sipuleucel-T or experimental immunotherapy
- No cancer pain requiring narcotics
- No history of autoimmune disease

PROSTVAC

Prostvac (PSA-TRICOM) in Preventing Disease Progression in Patients With Localized Prostate Cancer Undergoing Active Surveillance. For more information, visit: https://clinicaltrials.gov/show/NCT02326805

Agent: Prostvac-V/TRICOM is an immunotherapy vaccine that may encourage a cytotoxic T cell immune response against PSA-expressing tumor cells.
Purpose: Evaluate response in PSA and immune indicators to Prostvac-V
Enrollment: 150
Arm A: Prostvac-V/TRICOM
Arm B: placebo
Notable eligibility criteria:
- No prior treatment (including surgery, irradiation, local ablative, or androgen deprivation)
- No distant metastases
- No immunodeficiency or splenectomy

ADXS-PSA

ADXS31-142 Alone and in Combination With Pembrolizumab (MK-3475) in Patients With Prostate Cancer - KEYNOTE-046
For more information, visit: https://clinicaltrials.gov/show/NCT02325557

Agent: ADXS-PSA (or ADXS31-142), an immunotherapy, may drive an immune response to PSA-expressing cells by targeting prostate-specific antigen (PSA) associated with prostate cancer.
pembrolizumab (KEYTRUDA) may activate T-cell-mediated immune responses against tumor cells by binding to and inhibiting the programmed cell death-1 (PD-1) protein.
Purpose: Assess the safety and effectiveness (survival without disease progression) of immunotherapy ADXS-PSA.
Enrollment: 51
Part A (Phase 1): ADXS-PSA
Part B (Phase 1-2): ADXS-PSA + pembrolizumab
Notable eligibility criteria:
- Castrate-resistant metastatic disease
- No more than 3 prior treatment (chemotherapy, hormonal, or immunotherapy) in metastatic setting
- No more than 1 chemotherapy in metastatic setting
- No active autoimmune disease requiring systemic treatment within the past 2 years