Prostate CancerPhase 2NCT01875250
Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer
A Phase 2 study testing PROSTVAC-F (Fowlpox)/TRICOM, PROSTVAC-V (Vaccinia)/TRICOM and Enzalutamide (Xtandi) in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Enzalutamide is a well tolerated hormone therapy that is used to treat advanced prostate cancer. It is given to help kill cancer cells and limit cancer cell growth. A new possible way of treating prostate cancer is using a therapeutic cancer vaccine (immune stimulating therapy) that may help activate the… Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- PROSTVAC-F (Fowlpox)/TRICOM, PROSTVAC-V (Vaccinia)/TRICOM and Enzalutamide (Xtandi)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jul 2013to 28 Feb 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Biochemical progression defined as follows:
- For patients following definitive radiation therapy: a rise in prostate-specific antigen (PSA) of greater than or equal to 2 ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria).
- For patients following radical prostatectomy: rising PSA after surgical procedure. (Patients must have a PSA greater than or equal to 2ng/ml)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky greater than or equal to 80%).
- Patients must have a PSA doubling time of 12 months or less.
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- Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 month.
- Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no toxicity greater than or equal to grade 2.
- Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan for metastatic prostate cancer.
- Hematological eligibility parameters (within 16 days before starting therapy):
- Granulocyte count greater than or equal to 1000/mm(3)
- Platelet count greater than or equal to 100,000/mm(3)
- Hemoglobin (Hgb) greater than or equal to 10 g/dL
- Biochemical eligibility parameters (within 16 days before starting therapy):
- Hepatic function: bilirubin less than or equal to 1.5 mg/dL (OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 2.5 times upper limit of normal.
- No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses
- Willing to travel to the National Institutes of Health (NIH) for follow-up visits.
- 18 years of age or older.
- Able to understand and sign informed consent.
- Baseline testosterone greater than or equal to lower limit of normal.
- PSA less than or equal to 20 ng/mL.
- The effects of enzalutamide, PSA-TRICOM or the combination on the developing human fetus are unknown. For this reason, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
Who cannot join
- Immunocompromised status due to:
- Human immunodeficiency virus (HIV) positivity.
- Active autoimmune diseases such as Addison's disease, Hashimoto s thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Graves disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
- Other immunodeficiency diseases
- Chronic administration (defined as daily or every other day for continued use greater than 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PSA-TRICOM. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.
- Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program.
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- History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).
- Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (eg phytoestrogens and saw palmetto)
- History of prior chemotherapy
- History of prior immunotherapy within the last 3 years
- Major surgery within 4 weeks prior to enrollment (Day 1 visit).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or poxviral vaccines (e.g., vaccinia vaccine)
- Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
- History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
- Previous serious adverse reactions to smallpox vaccination
- Unable to avoid close contact or household contact with the following highrisk individuals for three weeks after the Day 1 vaccination: (a) children 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczematoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV).
- Receipt of an investigational agent within 30 days (or 60 days for an antibody based therapy) before the first planned dose of study drugs.
- Patients who test positive for Hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Use of herbal products that may decrease PSA levels (e.g. saw palmetto)
- Any gastrointestinal disease that could hinder the absorption of enzalutamide
- Uncontrolled hypertension (Systolic Blood Pressure (SBP)>170/ Diastolic Blood Pressure (DBP)>105)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer
Background:
- Enzalutamide is a well tolerated hormone therapy that is used to treat advanced prostate cancer. It is given to help kill cancer cells and limit cancer cell growth. A new possible way of treating prostate cancer is using a therapeutic cancer vaccine (immune stimulating therapy) that may help activate the immune system against the cancer. The immune stimulating vaccine will help white blood cells recognize and kill the cancer cells throughout the body. This vaccine therapy has been tested in hundreds of patients and is very well tolerated. Researchers want to see whether this vaccine, given with enzalutamide, is more effective at treating advanced prostate cancer than enzalutamide alone.
Read more
Objectives:
- To compare the safety and effectiveness of enzalutamide with and without vaccine therapy for advanced prostate cancer.
Key Eligibility:
- Men at least 18 years of age who have advanced castration sensitive prostate cancer.
- Patients must have testosterone within the normal range
- No evidence of metastatic prostate cancer on computed tomography (CT) or Bone scan
- No history of autoimmune diseases
- No previous immunotherapy within 3 years
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will be used to monitor the cancer before treatment.
- Participants will be separated into two groups. One group will have enzalutamide and the study vaccine. The other group will have enzalutamide alone.
- All participants will take enzalutamide once a day. They will take the drug for 3 months. This form of intermittent therapy is common in this population of patients.
- The vaccine group of participants will receive the new study vaccine. They will have a single injection on the first day of the first study cycle. There will be regular booster injections afterward. There will be one injection during the third week of treatment, and one in the fifth week. The vaccine will then be given every 4 weeks until 21 weeks have passed.
- Treatment will be monitored with frequent blood tests and imaging studies.
Read the detailed description
Background:
- Androgen deprivation therapy (ADT) and surveillance are standard therapy options for prostate cancer patients with biochemical progression after localized therapy (or nonmetastatic castration sensitive prostate cancer; nmCSPC also known as D0 Prostate Cancer). These patients cannot be cured of prostate cancer and the primary therapeutic goal is to contain the disease with anti-androgen therapy.
- ADT can be administered intermittently consisting of multiple short courses or continuously with similar long-term clinical outcomes.
- Previous studies with high dose bicalutamide (androgen receptor antagonist, ARA) have shown significant biochemical control in nmCSPC.
- Enzalutamide is a modern ARA with greater androgen receptor affinity than bicalutamide and further impairs downstream effects of androgen receptor activation. This agent is FDA approved for the treatment of chemotherapy refractory metastatic castration resistant prostate cancer.
- Given its favorable side effect profile, there is strong interest in using enzalutamide to treat patients with earlier stages of prostate cancer including nmCSPC.
- PSA-TRICOM (Prostvac; developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic, Mountain View, California (CA)) is a novel candidate prostate cancer immunotherapy for the treatment of prostate cancer. It is a viral vector based therapeutic cancer vaccine that is administered via subcutaneous injections. In a randomized controlled Phase 2 trial, PSA-TRICOM therapy was associated with a prolongation of survival in men with metastatic castrate-resistant prostate cancer. A phase III trial is currently enrolling patients in this same population.
- There is also rationale to use therapeutic cancer vaccines such as PSA-TRICOM in earlier stage prostate cancer patients to maximize the potential therapeutic effect of immune stimulating therapy.
- An ongoing NCI clinical trial that combined PSA-TRICOM with flutamide (an older Food and Drug Administration (FDA) approved ARA) in nonmetastatic castration resistant prostate cancer has demonstrated safety and suggested the potential to improve time to progression.
- Analysis of previous trials using therapeutic cancer vaccines alone and in combination suggests that such therapies may alter tumor growth rate. If this hypothesis is correct, a therapeutic cancer vaccine may alter tumor regrowth rate/recovery after a cytoreductive therapy such as enzalutamide is discontinued.
- If PSA-TRICOM with enzalutamide can result in a reduced tumor regrowth rate as measured by PSA after a short course of enzalutamide therapy, it would provide an important proof of concept and potentially define it more clear role for therapeutic cancer vaccines in prostate cancer and potentially other cancers.
- To prospectively evaluate this hypothesis, all patients will be treated with enzalutamide in a manner similar to how short course ADT is used in common clinical practice. Half the patients will also be given PSA-TRICOM and PSA recovery after enzalutamide therapy will be compared between patients who received vaccine and those who did not.
- Preliminary data from the first cohort of randomized patients suggests that enzalutamide alone can induce an immunologic response. A second cohort of 15 patients will explore a lower dose of enzalutamide at 80 mg to determine if similar immunologic responses can also be seen at a lower dose, where toxicity is less likely.
Objectives:
Primary Endpoint:
-Determine if PSA-TRICOM combined with the novel androgen receptor antagonist enzalutamide will result in a decrease in PSA growth kinetics (tumor re-growth rate) after enzalutamide discontinuation in patients with non-metastatic, castration sensitive prostate cancer (i.e. patients with normal testosterone).
Eligibility:
- Patients with nonmetastatic castration sensitive prostate cancer and a PSA over 2.0 ng/ml
- Patients with normal testosterone levels.
- Histologically confirmed adenocarcinoma.
- Patients with a PSA doubling time of 12 months or less.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
Design:
- Randomized pilot study
- Cohort 1:
- Thirty-four patients to be enrolled and randomized 1:1 to
- Arm A: Enzalutamide for 3 months.
- Arm B: Enzalutamide 3 months + PSA-TRICOM on weeks 1, 3,5,9,13,17 and 21.
Cohort 1:
- Arm A: Enzalutamide (n=17)
- Arm B: Enzalutamide + PSA-TRICOM (n=17)
- Enzalutamide will be given at the standard dose of 160 mg daily for 3 months. PSATRICOM (Prostvac-V/F) will consist of a single subcutaneous (sc) immunization of Prostvac-V in Week 1, followed by 6 Prostvac-F immunizations administered in Weeks 3, 5, 9, 13, 17, and 21. Patients will be retreated with a 3-month course of enzalutamide after PSA has returned to baseline values at study entry or higher. Patients will have had to be on study for at least 7 months or longer in order to be retreated with an additional course of enzalutamide therapy. Patients will be followed for PSA recovery after enzalutamide has been discontinued. Patients who do not develop a 25% decline in PSA after 3 months will not be evaluated for tumor re-growth and additional patients will be enrolled to evaluate for that endpoint. Patients will be stratified based on a doubling time of greater than or less than 6 months.
- Conditions
- Prostate Cancer
- Being tested
- PROSTVAC-F (Fowlpox)/TRICOM, PROSTVAC-V (Vaccinia)/TRICOM, Enzalutamide (Xtandi)
- Keywords
- Gene Transfer, Androgen Receptor Antagonist, PSA, Immune Response, Immunotherapy
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PROSTVAC-F (Fowlpox)/TRICOMBiological
Also called PROSTVAC-F/TRICOM
A recombinant fowlpox virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.
PROSTVAC-V (Vaccinia)/TRICOMBiological
Also called PROSTVAC-V/TRICOM
A recombinant vaccinia virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.
Enzalutamide (Xtandi)Drug
Also called Xtandi
An androgen receptor inhibitor.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Enzalutamide for 3 months | Experimental | Enzalutamide for 3 months Receives: Drug: Enzalutamide (Xtandi) |
| Arm B - Enzalutamide for 3 months + PSA-TRICOM | Experimental | Enzalutamide 3 months + PSA-TRICOM (Prostvac-V/F) on weeks 1, 3, 5, 9,13,17 and 21 Receives: Biological: PROSTVAC-F (Fowlpox)/TRICOM; Biological: PROSTVAC-V (Vaccinia)/TRICOM; Drug: Enzalutamide (Xtandi) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Growth Rate
Growth rate was measured using the growth rate equation -f(t) = exp (-d*t) + exp (g*t) -1 where exp is the base of the natural algorithm, e = 2.7182 and t is days since treatment started. The tumor growth rate equation measures Prostate Specific Antigen (PSA) rise over time. The UOM is unitless because this is a way to measure PSA kinetics.
Measured: 7 months
Secondary outcomes (5)
Mean Pretreatment Plasma Vascular Endothelial Growth Factor (VEGF) Concentration 30 Days After the Start of Course 1 and Course 2 of Enzalutamide
VEGF was measured by the enzyme-linked immunosorbent assay (ELISA) assay. The lower limit of quantitation of assay was 9.0 pg/ml.
Measured: 30 Days After the Start of Course 1 and Course 2 of Enzalutamide
Median Testosterone After 84 Days of Enzalutamide
Normal testosterone is 270-1070 nd/dL.
Measured: 84 days
Percent Change in Prostate Specific Antigen (PSA) After 84 Days of Enzalutamide in Course 1
Median PSA change would be considered optimal.
Measured: 84 days
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Measured: Date treatment consent signed to date off study, approximately 43 months and 13 days for Arm A, and 78 months and 6 days for Arm B.
Median Time Until Prostate Specific Antigen (PSA) Recovery From Baseline Following Course 1 and Course 2 of Enzalutamide
PSA recovery is defined as the return above baseline PSA in participants with normal testosterone and non-metastatic, castration sensitive prostate cancer.
Measured: up to 41 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2013 (estimated)
- Study start22 Jul 2013
- Primary completion1 Sep 2019
- Study completion28 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Ravi A. Madan, M.D., National Cancer Institute (NCI)
- Investigators
- Ravi A Madan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01875250
- Sponsor's protocol ID
- 130153
- Other IDs
- 13-C-0153
- Status last verified
- Sep 2020
- First submitted
- 7 Jun 2013
- Last updated
- 16 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Furr BJ. "Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies. Horm Res. 1989;32 Suppl 1:69-76. doi: 10.1159/000181315.
PubMed 2533159Chen Y, Clegg NJ, Scher HI. Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target. Lancet Oncol. 2009 Oct;10(10):981-91. doi: 10.1016/S1470-2045(09)70229-3.
PubMed 19796750Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M, Fontana JA, Chapman RA, Mills GM, Raghavan D, Crawford ED; Southwest Oncology Group. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer. 2008 Jun;112(11):2393-400. doi: 10.1002/cncr.23473.
PubMed 18383517Madan RA, Karzai F, Donahue RN, Al-Harthy M, Bilusic M, Rosner II, Singh H, Arlen PM, Theoret MR, Marte JL, Cordes L, Couvillon A, Hankin A, Williams M, Owens H, Lochrin SE, Chau CH, Steinberg S, Figg WD, Dahut W, Schlom J, Gulley JL. Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer. J Immunother Cancer. 2021 Mar;9(3):e001556. doi: 10.1136/jitc-2020-001556.
PubMed 33664086
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer
- ClinicalTrials.gov ID
- NCT01875250
- Acronym / sponsor ID
- 130153
- Conditions
- Prostate Cancer
- Keywords
- Gene Transfer, Androgen Receptor Antagonist, PSA, Immune Response, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 22 Jul 2013 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 28 Feb 2020 (actual)
- First posted
- 11 Jun 2013 (estimated)
- Results
- Posted 16 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Enzalutamide is a well tolerated hormone therapy that is used to treat advanced prostate cancer. It is given to help kill cancer cells and limit cancer cell growth. A new possible way of treating prostate cancer is using a therapeutic cancer vaccine (immune stimulating therapy) that may help activate the immune system against the cancer. The immune stimulating vaccine will help white blood cells recognize and kill the cancer cells throughout the body. This vaccine therapy has been tested in hundreds of patients and is very well tolerated. Researchers want to see whether this vaccine, given with enzalutamide, is more effective at treating advanced prostate cancer than enzalutamide alone.
Objectives:
- To compare the safety and effectiveness of enzalutamide with and without vaccine therapy for advanced prostate cancer.
Key Eligibility:
- Men at least 18 years of age who have advanced castration sensitive prostate cancer.
- Patients must have testosterone within the normal range
- No evidence of metastatic prostate cancer on computed tomography (CT) or Bone scan
- No history of autoimmune diseases
- No previous immunotherapy within 3 years
Design:
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will be used to monitor the cancer before treatment.
- Participants will be separated into two groups. One group will have enzalutamide and the study vaccine. The other group will have enzalutamide alone.
- All participants will take enzalutamide once a day. They will take the drug for 3 months. This form of intermittent therapy is common in this population of patients.
- The vaccine group of participants will receive the new study vaccine. They will have a single injection on the first day of the first study cycle. There will be regular booster injections afterward. There will be one injection during the third week of treatment, and one in the fifth week. The vaccine will then be given every 4 weeks until 21 weeks have passed.
- Treatment will be monitored with frequent blood tests and imaging studies.
Detailed description
Background:
- Androgen deprivation therapy (ADT) and surveillance are standard therapy options for prostate cancer patients with biochemical progression after localized therapy (or nonmetastatic castration sensitive prostate cancer; nmCSPC also known as D0 Prostate Cancer). These patients cannot be cured of prostate cancer and the primary therapeutic goal is to contain the disease with anti-androgen therapy.
- ADT can be administered intermittently consisting of multiple short courses or continuously with similar long-term clinical outcomes.
- Previous studies with high dose bicalutamide (androgen receptor antagonist, ARA) have shown significant biochemical control in nmCSPC.
- Enzalutamide is a modern ARA with greater androgen receptor affinity than bicalutamide and further impairs downstream effects of androgen receptor activation. This agent is FDA approved for the treatment of chemotherapy refractory metastatic castration resistant prostate cancer.
- Given its favorable side effect profile, there is strong interest in using enzalutamide to treat patients with earlier stages of prostate cancer including nmCSPC.
- PSA-TRICOM (Prostvac; developed by the National Cancer Institute [NCI] and licensed to Bavarian Nordic, Mountain View, California (CA)) is a novel candidate prostate cancer immunotherapy for the treatment of prostate cancer. It is a viral vector based therapeutic cancer vaccine that is administered via subcutaneous injections. In a randomized controlled Phase 2 trial, PSA-TRICOM therapy was associated with a prolongation of survival in men with metastatic castrate-resistant prostate cancer. A phase III trial is currently enrolling patients in this same population.
- There is also rationale to use therapeutic cancer vaccines such as PSA-TRICOM in earlier stage prostate cancer patients to maximize the potential therapeutic effect of immune stimulating therapy.
- An ongoing NCI clinical trial that combined PSA-TRICOM with flutamide (an older Food and Drug Administration (FDA) approved ARA) in nonmetastatic castration resistant prostate cancer has demonstrated safety and suggested the potential to improve time to progression.
- Analysis of previous trials using therapeutic cancer vaccines alone and in combination suggests that such therapies may alter tumor growth rate. If this hypothesis is correct, a therapeutic cancer vaccine may alter tumor regrowth rate/recovery after a cytoreductive therapy such as enzalutamide is discontinued.
- If PSA-TRICOM with enzalutamide can result in a reduced tumor regrowth rate as measured by PSA after a short course of enzalutamide therapy, it would provide an important proof of concept and potentially define it more clear role for therapeutic cancer vaccines in prostate cancer and potentially other cancers.
- To prospectively evaluate this hypothesis, all patients will be treated with enzalutamide in a manner similar to how short course ADT is used in common clinical practice. Half the patients will also be given PSA-TRICOM and PSA recovery after enzalutamide therapy will be compared between patients who received vaccine and those who did not.
- Preliminary data from the first cohort of randomized patients suggests that enzalutamide alone can induce an immunologic response. A second cohort of 15 patients will explore a lower dose of enzalutamide at 80 mg to determine if similar immunologic responses can also be seen at a lower dose, where toxicity is less likely.
Objectives:
Primary Endpoint:
-Determine if PSA-TRICOM combined with the novel androgen receptor antagonist enzalutamide will result in a decrease in PSA growth kinetics (tumor re-growth rate) after enzalutamide discontinuation in patients with non-metastatic, castration sensitive prostate cancer (i.e. patients with normal testosterone).
Eligibility:
- Patients with nonmetastatic castration sensitive prostate cancer and a PSA over 2.0 ng/ml
- Patients with normal testosterone levels.
- Histologically confirmed adenocarcinoma.
- Patients with a PSA doubling time of 12 months or less.
- Eastern Cooperative Oncology Group (ECOG) 0-1.
Design:
- Randomized pilot study
- Cohort 1:
- Thirty-four patients to be enrolled and randomized 1:1 to
- Arm A: Enzalutamide for 3 months.
- Arm B: Enzalutamide 3 months + PSA-TRICOM on weeks 1, 3,5,9,13,17 and 21.
Cohort 1:
- Arm A: Enzalutamide (n=17)
- Arm B: Enzalutamide + PSA-TRICOM (n=17)
- Enzalutamide will be given at the standard dose of 160 mg daily for 3 months. PSATRICOM (Prostvac-V/F) will consist of a single subcutaneous (sc) immunization of Prostvac-V in Week 1, followed by 6 Prostvac-F immunizations administered in Weeks 3, 5, 9, 13, 17, and 21. Patients will be retreated with a 3-month course of enzalutamide after PSA has returned to baseline values at study entry or higher. Patients will have had to be on study for at least 7 months or longer in order to be retreated with an additional course of enzalutamide therapy. Patients will be followed for PSA recovery after enzalutamide has been discontinued. Patients who do not develop a 25% decline in PSA after 3 months will not be evaluated for tumor re-growth and additional patients will be enrolled to evaluate for that endpoint. Patients will be stratified based on a doubling time of greater than or less than 6 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - Enzalutamide for 3 months | Experimental | Drug: Enzalutamide (Xtandi)Enzalutamide for 3 months |
| Arm B - Enzalutamide for 3 months + PSA-TRICOM | Experimental | Biological: PROSTVAC-F (Fowlpox)/TRICOM, Biological: PROSTVAC-V (Vaccinia)/TRICOM, Drug: Enzalutamide (Xtandi)Enzalutamide 3 months + PSA-TRICOM (Prostvac-V/F) on weeks 1, 3, 5, 9,13,17 and 21 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Biochemical progression defined as follows:
- For patients following definitive radiation therapy: a rise in prostate-specific antigen (PSA) of greater than or equal to 2 ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria).
- For patients following radical prostatectomy: rising PSA after surgical procedure. (Patients must have a PSA greater than or equal to 2ng/ml)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky greater than or equal to 80%).
Key exclusion criteria (21 listed)
- Immunocompromised status due to:
- Human immunodeficiency virus (HIV) positivity.
- Active autoimmune diseases such as Addison's disease, Hashimoto s thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Graves disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
- Other immunodeficiency diseases
- Chronic administration (defined as daily or every other day for continued use greater than 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PSA-TRICOM. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PROSTVAC-F (Fowlpox)/TRICOMAlso: PROSTVAC-F/TRICOMA recombinant fowlpox virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules. | Biological | Arm B - Enzalutamide for 3 months + PSA-TRICOM |
| PROSTVAC-V (Vaccinia)/TRICOMAlso: PROSTVAC-V/TRICOMA recombinant vaccinia virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules. | Biological | Arm B - Enzalutamide for 3 months + PSA-TRICOM |
| Enzalutamide (Xtandi)Also: XtandiAn androgen receptor inhibitor. | Drug | Arm A - Enzalutamide for 3 months, Arm B - Enzalutamide for 3 months + PSA-TRICOM |
Primary outcome
Tumor Growth Rate
Time frame: 7 months
Growth rate was measured using the growth rate equation -f(t) = exp (-d*t) + exp (g*t) -1 where exp is the base of the natural algorithm, e = 2.7182 and t is days since treatment started. The tumor growth rate equation measures Prostate Specific Antigen (PSA) rise over time. The UOM is unitless because this is a way to measure PSA kinetics.
5 secondary outcomes
Mean Pretreatment Plasma Vascular Endothelial Growth Factor (VEGF) Concentration 30 Days After the Start of Course 1 and Course 2 of Enzalutamide
Time frame: 30 Days After the Start of Course 1 and Course 2 of Enzalutamide
Median Testosterone After 84 Days of Enzalutamide
Time frame: 84 days
Percent Change in Prostate Specific Antigen (PSA) After 84 Days of Enzalutamide in Course 1
Time frame: 84 days
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Time frame: Date treatment consent signed to date off study, approximately 43 months and 13 days for Arm A, and 78 months and 6 days for Arm B.
Median Time Until Prostate Specific Antigen (PSA) Recovery From Baseline Following Course 1 and Course 2 of Enzalutamide
Time frame: up to 41 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2533159Furr BJ. "Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies. Horm Res. 1989;32 Suppl 1:69-76. doi: 10.1159/000181315.
- Background: PubMed 19796750Chen Y, Clegg NJ, Scher HI. Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target. Lancet Oncol. 2009 Oct;10(10):981-91. doi: 10.1016/S1470-2045(09)70229-3.
- Background: PubMed 18383517Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M, Fontana JA, Chapman RA, Mills GM, Raghavan D, Crawford ED; Southwest Oncology Group. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer. 2008 Jun;112(11):2393-400. doi: 10.1002/cncr.23473.
- Derived from this study: PubMed 33664086Madan RA, Karzai F, Donahue RN, Al-Harthy M, Bilusic M, Rosner II, Singh H, Arlen PM, Theoret MR, Marte JL, Cordes L, Couvillon A, Hankin A, Williams M, Owens H, Lochrin SE, Chau CH, Steinberg S, Figg WD, Dahut W, Schlom J, Gulley JL. Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer. J Immunother Cancer. 2021 Mar;9(3):e001556. doi: 10.1136/jitc-2020-001556.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi A Madan, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PROSTVAC-F (Fowlpox)/TRICOM, PROSTVAC-V (Vaccinia)/TRICOM and Enzalutamide (Xtandi) in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Growth Rate (time frame: 7 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01875250, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2020.