Prostate CancerPhase 2NCT00450463
Vaccine Therapy With PROSTVAC/TRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer
A Phase 2 study testing Sargramostim (GM-CSF, Leukine), Flutamide (Eulexin) and PROSTVAC-F/ TRICOM in people with Prostate Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
Background: Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease. The vaccine in this study consists of a priming vaccine called PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM (triad of… Read more about this study
- Who is it for?
- Ages 18 to 110 years, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Sargramostim (GM-CSF, Leukine), Flutamide (Eulexin) and PROSTVAC-F/ TRICOM
- Type of treatment
- Vaccines, Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 Feb 2007to 8 Jun 2017
- 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 110 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 prior to starting this study. 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.
- Must have non-metastatic androgen insensitive prostate cancer with a rising PSA (prostatic specific antigen) with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan. A rising PSA is defined as two consecutively rising PSA levels, separated by at least 1 month apart, with the last measurement that is greater than 1ng/ml. Patients on nilutamide therapy must undergo nilutamide withdrawal for at least 4 weeks and still show evidence of a rising PSA. Following treatment with bicalutamide, patients must undergo withdrawal for at least 6 weeks and still show evidence of a rising PSA.
- Life expectancy greater than or equal to 6 months.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
- No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
- Hematological eligibility parameters:
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- Granulocyte count greater than or equal to 1,500/mm(3).
- Platelet count greater than or equal to 100,000/mm(3)
- Hgb (Hemoglobin) greater than or equal to 9 Gm/dL
- Lymphocyte count greater than or equal to 500/mm(3).
- Biochemical eligibility parameters (within 16 days of starting therapy)
- -Hepatic function: Bilirubin less than or equal to 1.5 mg/dl, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than 2.5 times upper limit of normal
- No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.
- Willing to travel to the NIH for follow-up visits.
- 18 years of age or greater.
- Able to understand and sign informed consent.
- Must agree to use effective birth control (such as a condom) or abstinence during and for a period of 4 months after the last vaccination therapy. Patients must be willing to remain on chemical castration therapy, unless they have had surgical castration.
- Patients must have recovered from acute toxicities related to prior therapy or surgery.
- Parameters for assessment of baseline renal function:
- Serum creatinine less than or equal to 1.5 times the upper limit of normal OR creatinine clearance on a 24-h urine collection of greater than or equal to 60 mL/min.
Who cannot join
- Patients should have no evidence of being immunocompromised as listed below.
- Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects.
- Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. Nasal or inhaled steroid use is permitted.
- Patients who have undergone allogenic peripheral stem cell transplantation or solid organ transplantation requiring immunosuppression.
- Patients who test positive for active Hepatitis B or Hepatitis C infection.
- Patients should have no autoimmune diseases that have required treatment such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome, active Grave's disease.
Show all 17Show fewer
- History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen.
- Do not administer the recombinant vaccinia vaccine if the recipient, or for at least three weeks after vaccination, their close household contacts (close household contacts are those who share housing or have close physical contact) are: persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV (human immunodeficiency virus) infection.
- Serious intercurrent medical illness (e.g., one that requires treatment) which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.
- Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with ordinary physical activity (New York Heart Association class 2 or greater) are not eligible.
- Patients with a history of congestive heart failure or who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.
- Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible.
- Concurrent chemotherapy.
- No known brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis.
- Patients with a serious hypersensitivity reaction to egg products are not eligible.
- Prior splenectomy.
- Patients who have received prior flutamide therapy in the last year. (Patients treated with flutamide in the neoadjuvant or adjuvant setting or those previously treated with flutamide who did not have a rising PSA on treatment would be allowed to enroll on the protocol.)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
Official title: A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
Background:
- Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease.
- The vaccine in this study consists of a priming vaccine called PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM (triad of costimulatory molecules), made from vaccinia virus, and a boosting vaccine called PROSTVAC-F/TRICOM, made from fowlpox virus. DNA (Deoxyribonuceic acid) is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen (PSA) a protein that is normally produced by the patients tumor cells.
- GM-CSF (granulocyte macrophage colony stimulating factor), given along with the vaccine, is a chemical that boosts the immune system. It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site.
Read more
Objectives:
-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer.
Eligibility:
- Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland.
- Patients with a rising PSA (prostatic specific antigen) who have already been treated with anti-iandrogen therapy (either bicalutamide or nilutamide).
Design:
- There are two treatment groups in this study. Group A receives only flutamide; group B receive flutamide plus vaccine.
- Patients in both groups receive flutamide by mouth three times a day.
- Patients in group B receive PROSTVAC-V/TRICOM on day 1 and PROSTVAC-F/TRICOM on day 29 and again every 4 weeks. All vaccines are given as injections under the skin.
- Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens.
- After 3 months of therapy, patients receiving in group A (flutamide alone) may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread. Patients in group B (flutamide plus vaccine) stop flutamide and may continue vaccine therapy. At this point patients may continue to receive treatment until the disease progresses or PSA levels rise....
Read the detailed description
Background:
- There is no standard of care for prostate cancer patients progressing on hormone therapy with a rising serum PSA (prostatic specific antigen) level without evidence of metastatic disease.
- We have completed a phase II trial in which men with this stage of disease were randomized to receive a pox vector PSA vaccine vs. the antiandrogen nilutamide.
- The median time to treatment failure on nilutamide was 7.6 months.
- 12 patients on the vaccine arm had nilutamide added at the time of PSA progression.
- The median time for treatment failure after the addition of nilutamide was 13.9 months, for a total of 25.9 months from initiation of vaccine therapy.
- This suggests that the combination of hormone therapy with vaccine therapy may lead to an improved clinical benefit compared to hormone therapy alone.
- Due to the increased toxicity of nilutamide compared to other antiandrogens and the patients prior exposure to bicalutamide therapy, we plan to use flutamide as a second line hormonal manipulation in the below study.
Objectives (Primary):
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone.
Eligibility:
- Must have non metastatic androgen insensitive prostate cancer with a rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan.
- Hgb (hemoglobin) greater than or equal to 9 g/dL.
- Lymphocyte count greater than or equal to 500/mm(3).
- Hepatic function: Bilirubin less than or equal to 1.5 mg/dL, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than 2.5 times upper limit of normal
Design:
-Flutamide will be administered at a dose of 250 mg PO (by mouth) tid (three times a day) every day in both arms A and B.
rV-PSATRICOM will be administered s.c. (subcutaneous) on day 1 in Arm B.
rF-PSATRICOM will be administered s.c. on day 29 \& every 4 weeks in Arm B.
- For patients with declining PSA no restaging will be done unless they develop symptoms consistent with metastatic disease.
- For patients with rising PSA, once 2 consecutive PSA rises are seen, a CT will be done at their next scheduled visit. They will then be re-staged (CT and bone scans) at 3 month intervals as long as PSA continues to rise.
- After 3 months of therapy, patients receiving the flutamide alone (arm A) may cross over to receive vaccine if they develop a rising PSA and scans are without metastatic disease. The vaccine may commence 4 weeks after flutamide is stopped if the PSA continues to rise. If there is an antiandrogen withdrawal response (a decline in PSA 28 days after the discontinuation of flutamide), PSA serum levels will be checked every 28 days and vaccine may commence when the serum PSA levels begin to rise (if scans are negative for metastatsis). Patients on arm B will have flutamide discontinued and may continue vaccine therapy. At this point patients may continue to receive treatment on study until the development of disease on scans or a second occurrence of clinical progression.
- Patients who have been on study for 2 years or more with stable disease and who are not getting vaccine, clinic visits may be scheduled every 8 weeks. (Patients receiving monthly vaccine will continue to have monthly visits.)
- For patients who have stable disease and attend clinic every 8 weeks, once 2 consecutive PSA rises are seen, a CT and bone scan will be done at their next visit in 4 weeks. They will then be restaged (CT and bone scans) at 3 month intervals as long as PSA continues to rise.
- Conditions
- Prostate Cancer
- Being tested
- Sargramostim (GM-CSF, Leukine), Flutamide (Eulexin), PROSTVAC-F/ TRICOM, PROSTVAC-V/TRICOM
- Keywords
- Immunotherapy, Hormonal Therapy, Combination Therapy, Prostate Specific Antigen, Immunoassay, Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sargramostim (GM-CSF, Leukine)Drug
Also called GM-CSF
A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast.
Flutamide (Eulexin)Drug
Also called Eulexin
Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.
PROSTVAC-F/ TRICOMBiological
Also called PROSTVAC-F (rilimogene galvacirepvec/rilimogene glafolivec)/TRICOM (triad of costimulatory molecules
A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three costimulatory molecules.
PROSTVAC-V/TRICOMBiological
A recombinant vaccinia virus vector vaccine containing the genes for human prostatic specific antigen (PSA) and three co-stimulatory molecules.
| Study group | Role | What they receive |
|---|---|---|
| Flutamide Alone | Active comparator | Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued. Receives: Drug: Flutamide (Eulexin) |
| Flutamide + Vaccine + Sargramostim | Experimental | Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment. Receives: Drug: Sargramostim (GM-CSF, Leukine); Drug: Flutamide (Eulexin); Biological: PROSTVAC-F/ TRICOM; Biological: PROSTVAC-V/TRICOM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Treatment Failure
Time to treatment failure is defined as a rising Prostatic Specific Antigen (PSA) (Bubley criteria, JCO 1999), development of metastatic disease, or removal from treatment due to excessive toxicity) compared to patients receiving flutamide alone. Normal PSA is 4.0 ng/mL or lower.
Measured: Median Potential Follow-up of 46.7 months
Secondary outcomes (3)
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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: Median Potential Follow-up of 46.7 months
Number of Participants With Prostatic Specific Antigen (PSA) Response
Complete response is PSA <0.2 confirmed by a second reading at least 4 weeks later. All patients with a PSA decline of >50% (confirmed by a second value at least 4 weeks after the first) and who have no other evidence of disease progression will be reported with both PSA decline only and PSA decline and stable disease on scans. A 25% increase in PSA over nadir is progressive disease with or without evidence of metastatic disease, and/or development of disease on scans or a second occurrence of rising PSA levels in the absence of clinical progression.
Measured: Median potential follow-up for all patients is 46.7 months
Percentage of Participants With Antigen Specific Immune Responses Against Prostatic Specific Antigen (PSA)
Antigen specific responses were evaluated using intracellular cytokine staining of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) cells (evaluating cluster of Differentiation 107a (CD107a), INFg, Interleukin-2 (IL-2), and tumor necrosis factor (TNF) for CD4+ and CD8+ T-cells. Peripheral blood mononuclear cells were separated by Ficoll-Hypaque density gradient separation, washed three times, and preserved in 90% heat-inactivated human A and B blood-type antigens) AB serum and 10% Dimethyl sulfoxide (DMSO) in liquid nitrogen at a concentration of 1 × 10^7 cells/mL until assayed. Analysis of antigen-specific responses following therapy was assessed by intracellular cytokine staining following a period of in vitro stimulation with overlapping 15-mer peptide pools. A more complete description can be found at Heery CR et al, Cancer Immunol Res. 2015 Nov;3(11):1248-56.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2007 (estimated)
- Study start23 Feb 2007
- Primary completion27 Apr 2017
- Study completion8 Jun 2017
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
- 64 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
- NCT00450463
- Sponsor's protocol ID
- 070107
- Other IDs
- 07-C-0107
- Status last verified
- Nov 2018
- First submitted
- 20 Mar 2007
- Last updated
- 29 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. doi: 10.3322/canjclin.55.1.10.
PubMed 15661684Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
PubMed 10655437Dillioglugil O, Leibman BD, Kattan MW, Seale-Hawkins C, Wheeler TM, Scardino PT. Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer. Urology. 1997 Jul;50(1):93-9. doi: 10.1016/S0090-4295(97)00106-4.
PubMed 9218025Madan RA, Bilusic M, Stein MN, Donahue RN, Arlen PM, Karzai F, Plimack E, Wong YN, Geynisman DM, Zibelman M, Mayer T, Strauss J, Chen G, Rauckhorst M, McMahon S, Couvillon A, Steinberg S, Figg WD, Dahut WL, Schlom J, Gulley JL. Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer. Oncologist. 2023 Jul 5;28(7):642-e561. doi: 10.1093/oncolo/oyad058.
PubMed 37134294
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC/TRICOM and Flutamide vs. Flutamide Alone in Men With Androgen Insensitive, Non-Metastatic (D0.5) Prostate Cancer
- ClinicalTrials.gov ID
- NCT00450463
- Acronym / sponsor ID
- 070107
- Conditions
- Prostate Cancer
- Keywords
- Immunotherapy, Hormonal Therapy, Combination Therapy, Prostate Specific Antigen, Immunoassay, Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 23 Feb 2007 (actual)
- Primary completion
- 27 Apr 2017 (actual)
- Study completion
- 8 Jun 2017 (actual)
- First posted
- 22 Mar 2007 (estimated)
- Results
- Posted 26 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease.
- The vaccine in this study consists of a priming vaccine called PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM (triad of costimulatory molecules), made from vaccinia virus, and a boosting vaccine called PROSTVAC-F/TRICOM, made from fowlpox virus. DNA (Deoxyribonuceic acid) is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen (PSA) a protein that is normally produced by the patients tumor cells.
- GM-CSF (granulocyte macrophage colony stimulating factor), given along with the vaccine, is a chemical that boosts the immune system. It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site.
Objectives:
-To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer.
Eligibility:
- Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland.
- Patients with a rising PSA (prostatic specific antigen) who have already been treated with anti-iandrogen therapy (either bicalutamide or nilutamide).
Design:
- There are two treatment groups in this study. Group A receives only flutamide; group B receive flutamide plus vaccine.
- Patients in both groups receive flutamide by mouth three times a day.
- Patients in group B receive PROSTVAC-V/TRICOM on day 1 and PROSTVAC-F/TRICOM on day 29 and again every 4 weeks. All vaccines are given as injections under the skin.
- Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens.
- After 3 months of therapy, patients receiving in group A (flutamide alone) may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread. Patients in group B (flutamide plus vaccine) stop flutamide and may continue vaccine therapy. At this point patients may continue to receive treatment until the disease progresses or PSA levels rise....
Detailed description
Background:
- There is no standard of care for prostate cancer patients progressing on hormone therapy with a rising serum PSA (prostatic specific antigen) level without evidence of metastatic disease.
- We have completed a phase II trial in which men with this stage of disease were randomized to receive a pox vector PSA vaccine vs. the antiandrogen nilutamide.
- The median time to treatment failure on nilutamide was 7.6 months.
- 12 patients on the vaccine arm had nilutamide added at the time of PSA progression.
- The median time for treatment failure after the addition of nilutamide was 13.9 months, for a total of 25.9 months from initiation of vaccine therapy.
- This suggests that the combination of hormone therapy with vaccine therapy may lead to an improved clinical benefit compared to hormone therapy alone.
- Due to the increased toxicity of nilutamide compared to other antiandrogens and the patients prior exposure to bicalutamide therapy, we plan to use flutamide as a second line hormonal manipulation in the below study.
Objectives (Primary):
-To determine if use of a combination of vaccine plus flutamide may be associated with a trend toward improvement in time to treatment failure compared to flutamide alone.
Eligibility:
- Must have non metastatic androgen insensitive prostate cancer with a rising PSA with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan.
- Hgb (hemoglobin) greater than or equal to 9 g/dL.
- Lymphocyte count greater than or equal to 500/mm(3).
- Hepatic function: Bilirubin less than or equal to 1.5 mg/dL, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than 2.5 times upper limit of normal
Design:
-Flutamide will be administered at a dose of 250 mg PO (by mouth) tid (three times a day) every day in both arms A and B.
rV-PSATRICOM will be administered s.c. (subcutaneous) on day 1 in Arm B.
rF-PSATRICOM will be administered s.c. on day 29 \& every 4 weeks in Arm B.
- For patients with declining PSA no restaging will be done unless they develop symptoms consistent with metastatic disease.
- For patients with rising PSA, once 2 consecutive PSA rises are seen, a CT will be done at their next scheduled visit. They will then be re-staged (CT and bone scans) at 3 month intervals as long as PSA continues to rise.
- After 3 months of therapy, patients receiving the flutamide alone (arm A) may cross over to receive vaccine if they develop a rising PSA and scans are without metastatic disease. The vaccine may commence 4 weeks after flutamide is stopped if the PSA continues to rise. If there is an antiandrogen withdrawal response (a decline in PSA 28 days after the discontinuation of flutamide), PSA serum levels will be checked every 28 days and vaccine may commence when the serum PSA levels begin to rise (if scans are negative for metastatsis). Patients on arm B will have flutamide discontinued and may continue vaccine therapy. At this point patients may continue to receive treatment on study until the development of disease on scans or a second occurrence of clinical progression.
- Patients who have been on study for 2 years or more with stable disease and who are not getting vaccine, clinic visits may be scheduled every 8 weeks. (Patients receiving monthly vaccine will continue to have monthly visits.)
- For patients who have stable disease and attend clinic every 8 weeks, once 2 consecutive PSA rises are seen, a CT and bone scan will be done at their next visit in 4 weeks. They will then be restaged (CT and bone scans) at 3 month intervals as long as PSA continues to rise.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Flutamide Alone | Active comparator | Drug: Flutamide (Eulexin)Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued. |
| Flutamide + Vaccine + Sargramostim | Experimental | Drug: Sargramostim (GM-CSF, Leukine), Drug: Flutamide (Eulexin), Biological: PROSTVAC-F/ TRICOM, Biological: PROSTVAC-V/TRICOMPatients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment. |
Who may qualify
- Ages
- 18 to 110 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the: National Institutes of Health (NIH) Clinical Center prior to starting this study. 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.
- Must have non-metastatic androgen insensitive prostate cancer with a rising PSA (prostatic specific antigen) with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan. A rising PSA is defined as two consecutively rising PSA levels, separated by at least 1 month apart, with the last measurement that is greater than 1ng/ml. Patients on nilutamide therapy must undergo nilutamide withdrawal for at least 4 weeks and still show evidence of a rising PSA. Following treatment with bicalutamide, patients must undergo withdrawal for at least 6 weeks and still show evidence of a rising PSA.
- Life expectancy greater than or equal to 6 months.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
- No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
Key exclusion criteria (17 listed)
- Patients should have no evidence of being immunocompromised as listed below.
- Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects.
- Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. Nasal or inhaled steroid use is permitted.
- Patients who have undergone allogenic peripheral stem cell transplantation or solid organ transplantation requiring immunosuppression.
- Patients who test positive for active Hepatitis B or Hepatitis C infection.
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 |
|---|---|---|
| Sargramostim (GM-CSF, Leukine)Also: GM-CSFA recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast. | Drug | Flutamide + Vaccine + Sargramostim |
| Flutamide (Eulexin)Also: EulexinOrally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex. | Drug | Flutamide + Vaccine + Sargramostim, Flutamide Alone |
| PROSTVAC-F/ TRICOMAlso: PROSTVAC-F (rilimogene galvacirepvec/rilimogene glafolivec)/TRICOM (triad of costimulatory moleculesA recombinant fowlpox virus vector vaccine containing the genes for human PSA and three costimulatory molecules. | Biological | Flutamide + Vaccine + Sargramostim |
| PROSTVAC-V/TRICOMA recombinant vaccinia virus vector vaccine containing the genes for human prostatic specific antigen (PSA) and three co-stimulatory molecules. | Biological | Flutamide + Vaccine + Sargramostim |
Primary outcome
Time to Treatment Failure
Time frame: Median Potential Follow-up of 46.7 months
Time to treatment failure is defined as a rising Prostatic Specific Antigen (PSA) (Bubley criteria, JCO 1999), development of metastatic disease, or removal from treatment due to excessive toxicity) compared to patients receiving flutamide alone. Normal PSA is 4.0 ng/mL or lower.
3 secondary outcomes
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Time frame: Median Potential Follow-up of 46.7 months
Number of Participants With Prostatic Specific Antigen (PSA) Response
Time frame: Median potential follow-up for all patients is 46.7 months
Percentage of Participants With Antigen Specific Immune Responses Against Prostatic Specific Antigen (PSA)
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15661684Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. doi: 10.3322/canjclin.55.1.10.
- Background: PubMed 10655437Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
- Background: PubMed 9218025Dillioglugil O, Leibman BD, Kattan MW, Seale-Hawkins C, Wheeler TM, Scardino PT. Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer. Urology. 1997 Jul;50(1):93-9. doi: 10.1016/S0090-4295(97)00106-4.
- Derived from this study: PubMed 37134294Madan RA, Bilusic M, Stein MN, Donahue RN, Arlen PM, Karzai F, Plimack E, Wong YN, Geynisman DM, Zibelman M, Mayer T, Strauss J, Chen G, Rauckhorst M, McMahon S, Couvillon A, Steinberg S, Figg WD, Dahut WL, Schlom J, Gulley JL. Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer. Oncologist. 2023 Jul 5;28(7):642-e561. doi: 10.1093/oncolo/oyad058.
- 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)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sargramostim (GM-CSF, Leukine), Flutamide (Eulexin) and PROSTVAC-F/ TRICOM in people with Prostate Cancer, run by National Cancer Institute (NCI) at 3 sites 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 20 inclusion and 17 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 29 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 26 Nov 2018). 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?
Time to Treatment Failure (time frame: Median Potential Follow-up of 46.7 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 NCT00450463, 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 29 Nov 2018.