Prostate CancerPhase 2NCT00450619
153Sm-EDTMP With or Without a PSA/TRICOM Vaccine To Treat Men With Androgen-Insensitive Prostate Cancer
A Phase 2 study testing Samarium Sm 153 lexidronam pentasodium, Sargramostim and Recombinant vaccinia-TRICOM vaccine in people with Prostate Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
Background: No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy. An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Samarium Sm 153 lexidronam pentasodium, Sargramostim and Recombinant vaccinia-TRICOM vaccine
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2007to Nov 2012
- 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 years and older
- 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, National Institutes of Health (NIH), the National Naval Medical Center, or Walter Reed Army Medical Center; or participating Institute's Department of Pathology prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Must have metastatic castration resistant prostate cancer (CRPC) with at least 2 bone lesions consistent with prostate cancer metastasis and progressive disease (2 rising PSA values separated by at least one week, new or enlarging lesions consistent with prostate cancer, or clinical progression) on docetaxel for metastatic prostate cancer or inability to tolerate docetaxel.
- Life expectancy greater than or equal to 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
- Hematological eligibility parameters (within 16 days of starting therapy).
Show all 21Show fewer
- Granulocyte count greater than or equal to 1,500/mm^3
- Platelet (PLT) count greater than or equal to 100,000/mm^3
- Hemoglobin (Hgb) greater than or equal to 10 Gm/dL (Transfusion may be given to accomplish this)
- Biochemical eligibility parameters (within 16 days of starting therapy)
- -Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times upper limit of normal; bilirubin less than 1.5 mg/dL OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL.
- No other active malignancies within the past 12 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder and treated with curative intent) or life-threatening illnesses.
- Willing to travel to the National Institutes of Health (NIH) or participating Institute for follow-up visits.
- 18 years of age or greater.
- Able to understand and sign informed consent.
- Agree to use adequate contraception prior to study entry and for at least 4 months following the last vaccine injection.
- Patients must remain on medical castration therapy with testosterone-suppressing therapy (e.g., gonadotropin releasing hormone (GnRH) agonist), unless they have had surgical castration.
- Patients must have recovered from acute toxicities related to prior therapy or surgery. For chemotherapy, typically this is 3 to 4 weeks.
- Patients who are incontinent of urine should be willing to undergo bladder catheterization to minimize the risk of radioactive contamination of clothing, bed linen, and the patient's environment.
- Concurrent treatment with bisphosphonates is allowed. If bisphosphonates have been given within 2 weeks prior to planned (153)Sm-EDTMP, then a 99Tc whole-body scintigraphy (bone scan) will be performed to confirm uptake into lesions. Bisphosphonates will not be given within 48 hours after (153)Sm-EDTMP administration.
- Serum creatinine less than or equal to 1.5 times 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, as listed below, of being immunocompromised:
- Human immunodeficiency virus (HIV) positivity due to the potential for decreased tolerance and risk for severe side effects.
- Hepatitis B or C positivity.
- Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. This is to avoid immunosuppression which may lead to potential complications with vaccinia (priming vaccination). Nasal or inhaled steroid use is permitted.
- Patients should have no autoimmune diseases that have required treatment, such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, or active Grave's 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 tract (GI) tract, will be allowed.
- History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen. Note: prior vaccination with vaccinia is not required.
Show all 21Show fewer
- Do not administer the recombinant vaccinia vaccine if the recipient or, for at least 3 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 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 a history of cardiomyopathy or symptomatic congestive heart failure (unless stable on treatment), symptomatic arrhythmia not controlled by medication. Unstable atherosclerotic heart disease (e.g. unstable angina) who require active intervention and history of myocardial infarction or embolic stroke within the past 6 months.
- Patients with cardiac disease who 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, unless the underlying cause has been treated and patient has documented normal ejection fraction.
- Patients with pulmonary disease who have fatigue or dyspnea with ordinary physical activity are not eligible.
- Concurrent chemotherapy.
- No brain metastasis or history of seizures, encephalitis, or multiple sclerosis.
- Serious hypersensitivity reaction to egg products.
- Prior splenectomy.
- Contraindicated in patients who have known hypersensitivity to EDTMP or similar phosphonate compounds.
- Patients with symptomatic soft tissue disease or parenchymal disease will be excluded.
- Radiation therapy to bone within 4 weeks of study entry.
- Patients previously treated with (153)Sm-EDTMP will be excluded.
- Patients requiring urgent local radiotherapy or orthopedic stabilization.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
University of Chicago
Chicago, Illinois, 60637
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
About this study
Official title: A Randomized Phase 2.5 Study of (153)Sm-EDTMP (Quadramet) With or Without a PSA/TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer
Background:
- No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy.
- An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The vaccine can trigger the immune system to make cells that may be able to recognize and attack the cancer cells that make PSA.
- Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is usually given to increase a patient's white blood cell count or to stimulate the immune system.
- 1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive drug that has been approved for many years to treat advanced prostate cancer. It is given through a vein and can be targeted directly to tumors in the bone where it can relieve pain caused by bone lesions. Radiation also increases the level of certain proteins inside the tumor, making it easier for the immune system to find and kill the tumor cells.
- When laboratory mice were given just vaccine, just radiation, or a combination of both, the combination was most effective in treating tumors.
Read more
Objectives:
-To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can delay progression of prostate cancer better than radiation alone.
Eligibility:
-Patients who have advanced prostate cancer that has worsened despite treatments with hormones, have two or more bone lesions related to their prostate cancer, and have had prior treatment with docetaxel chemotherapy.
Design:
- Patients are randomly assigned to receive radiation alone (Arm A) or radiation with vaccine and sargramostim (Arm B).
- Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12 weeks.
- Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given as injections under the skin, usually in the thigh. Radiation therapy is given through a vein.
- Patients are monitored regularly with physical examinations, blood and urine tests, and scans to evaluate safety and treatment response.
- Patients who are human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for obtaining immune cells called lymphocytes to measure the immune response to the vaccine.
Read the detailed description
Background
- There are no standard therapy options shown to prolong survival for patients with progressive disease on first-line docetaxel-based regimens for men with metastatic castration resistant prostate cancer (CRPC).
- Ninety percent of men in this population have bone metastasis.
- PSA/TRICOM vaccines as single agents can induce generation of PSA-specific T cells in the majority of patients and objective responses and PSA declines in a minority of patients. Furthermore, the generation of at least a 6-fold increase in PSA-specific T cells was significantly correlated with evidence of clinical benefit.
- Radiation can alter the phenotype of tumor cells (increase Fas, increase major histocompatibility complex (MHC), increase tumor-associated molecules and increase ICAM), making them much more amenable to immune-mediated killing.
- (153)Sm EDTMP is a beta emitter (with some gamma emissions) that targets osteoblastic bone lesions (such as those found in prostate cancer).
- (153)Sm EDTMP, at Food And Drug Administration (FDA)-approved doses used clinically for palliation of prostate cancer, can cause phenotypic changes in tumor cells, leading to improved killing of those cells in a cytotoxic T-cell assay in vitro.
- The combination of vaccine and radiation greatly increases antitumor efficacy in a murine subcutaneous tumor model.
Objectives
- Primary-A comparison of progression-free survival at 4 months between Arm A (153)Sm EDTMP alone) and Arm B (153Sm EDTMP with vaccine).
- Secondary-Objective responses, PSA outcomes, immunologic responses, toxicity, palliation and overall survival.
Eligibility
- Patients with metastatic CRPC who have 2 or more bone lesions consistent with prostate cancer and who have been treated with a docetaxel-based regimen.
- Patients with symptomatic soft tissue disease or parenchymal disease will be excluded.
Design
- Randomized phase 2.5 study.
- Sixty-eight patients to be enrolled and randomized to:
- Arm A: (153)Sm-EDTMP: 1 mCi/kg intravenous (IV) over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery.
Arm B: PROSTAC-V/TRICOM (vaccinia) 2 x 10^8 plaque forming unit (pfu) subcutaneously on day 1.
- (153)Sm-EDTMP: 1 mCi/kg IV over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery. PROSTVAC-F/TRICOM (fowlpox) 1 x 10^9 pfu subcutaneously on days 15, 29, and then every 4 weeks.
- Conditions
- Prostate Cancer
- Being tested
- Samarium Sm 153 lexidronam pentasodium, Sargramostim, Recombinant vaccinia-TRICOM vaccine, Recombinant fowlpox-TRICOM vaccine
- Keywords
- Radionuclide, Immunotherapy, Radiation, PSA, Hormone Refractory Prostate Cancer, 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.
Samarium Sm 153 lexidronam pentasodiumRadiation
1 mCi/Kg given intravenous (IV)over 1 minute on day 8.
SargramostimBiological
100 mcg/injection x 4 days given subcutaneously
Recombinant vaccinia-TRICOM vaccineBiological
2 x 10^8 PFU given subcutaneously on day 1.
Recombinant fowlpox-TRICOM vaccineBiological
1 x 10^9 PFU given subcutaneously on days 15 and 29
| Study group | Role | What they receive |
|---|---|---|
| Arm A -EDTMP Alone | Experimental | Patients receive samarium Sm 153 lexidronam pentasodium 1 mCi/Kg intravenous (IV) over 1 minute on day 8. Treatment repeats every 12 weeks in the absence of disease progression or unacceptable toxicity. Receives: Radiation: Samarium Sm 153 lexidronam pentasodium |
| Arm B - 153SmEDTMP with vaccine | Experimental | Patients receive recombinant vaccinia-TRICOM vaccine 2 x 10^8 PFU subcutaneously (SC) on day 1. Patients also receive recombinant fowlpox-TRICOM vaccine 1 x 10^9 PFU SC on days 15 and 29 and sargramostim (GM-CSF)100 mcg/injection SC x 4 days. Treatment with recombinant fowlpox-TRICOM vaccine and GM-CSF* repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive samarium Sm 153 lexidronam pentasodium 1 mCi/Kg as in arm I. Receives: Radiation: Samarium Sm 153 lexidronam pentasodium; Biological: Sargramostim; Biological: Recombinant vaccinia-TRICOM vaccine; Biological: Recombinant fowlpox-TRICOM vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Stable Disease at 4 Months.
Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started. Partial response (PR) is at least a 30% increase in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions on computed tomography (CT) or two or more lesions on bone scan.
Measured: 4.7 months
Progression Free Survival (PFS)
PFS is defined as the time to progress or die after the start of the therapy.
Measured: 4 months
Secondary outcomes (9)
Toxicity
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Measured: 5 years, 5 months
Number of Participants With Prostate-Specific Antigen (PSA) ≥ 30%
PSA is defined by the PSA Working Group criteria. A minimum PSA decline of at least 50% must be confirmed by a second PSA value 4 or more weeks later.
Measured: 4 months
Number of Participants With Prostate-Specific Antigen (PSA) ≥50%
PSA is defined by the PSA Working Group criteria. A minimum PSA decline of at least 50% must be confirmed by a second PSA value 4 or more weeks later.
Measured: 4 months
Overall Survival
Time from treatment start date until date of death or date last known alive.
Measured: From date of randomization until death or last follow up, whichever comes first, assessed up to 14 months.
Arm A: Prostate-Specific Antigen (PSA) T-cell Responses Post-vs. Pre-treatment
PSA T-cell responses were measured by fluorescence activated cell sorting (FACS)-based assay for T-cells expressing type I cytokines interferon (IFN-ϓ), interleukin 2 (IL2), tumor necrosis factor alpha (TNF-a) and/or lysosome-associated membrane protein (CD107a).
Measured: Approximately 60 days
Arm B: Prostate-Specific Antigen (PSA) T-cell Responses Post-vs. Pre-treatment
PSA T-cell responses were measured by fluorescence activated cell sorting (FACS)-based assay for T-cells expressing type I cytokines interferon (IFN-ϓ), interleukin 2 (IL2), tumor necrosis factor alpha (TNF-a) and/or lysosome-associated membrane protein (CD107a).
Measured: Approximately 60 days
Objective Response (Complete Response + Partial Response)
Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% increase in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Measured: 4 weeks
Palliation: Pain at Baseline
Subjective report of participant pain at baseline.This data reflects National Cancer Institute (NCI) patients only. This data was not systematically captured, so these results are based on subjective patient reports of improvement in pain on a scale of 1-10 post quadramet (samarium) as documented in the progress notes. 1-2 equals mild pain and 9-10 equals worst possible pain.
Measured: Baseline
Palliation: Improvement in Baseline Pain
Subjective report of participant pain at baseline. This data reflects National Cancer Institute (NCI) patients only. This data was not systematically captured, so these results are based on subjective patient reports of improvement in pain on a scale of 1-10 post quadramet (samarium) as documented in the progress notes. 1-2 equals mild pain and 9-10 equals worst possible pain.
Measured: post quadramet (samarium)
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 startFeb 2007
- Primary completionNov 2012
- Study completionNov 2012
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 (5)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
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, James Gulley, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- James L Gulley, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00450619
- Sponsor's protocol ID
- 070106
- Other IDs
- 07-C-0106
- Status last verified
- Nov 2016
- First submitted
- 20 Mar 2007
- Last updated
- 4 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Turner JH, Claringbold PG. A phase II study of treatment of painful multifocal skeletal metastases with single and repeated dose samarium-153 ethylenediaminetetramethylene phosphonate. Eur J Cancer. 1991;27(9):1084-6. doi: 10.1016/0277-5379(91)90297-q.
PubMed 1720321Simon RM, Steinberg SM, Hamilton M, Hildesheim A, Khleif S, Kwak LW, Mackall CL, Schlom J, Topalian SL, Berzofsky JA. Clinical trial designs for the early clinical development of therapeutic cancer vaccines. J Clin Oncol. 2001 Mar 15;19(6):1848-54. doi: 10.1200/JCO.2001.19.6.1848.
PubMed 11251017Therasse 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 10655437Christopher Ryan Heery, Ravi A. Madan, Marijo Bilusic, Joseph W. Kim, Nishith K. Singh, Myrna Rauckhorst, Clara Chen, William L. Dahut, Walter Michael Stadler, Robert S. DiPaola, Mark N. Stein, James W. Hodge, Jeffrey Schlom, James L. Gulley; Interim analysis of a phase II randomized clinical trial of samrium-153 (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer after docetaxel. J Clin Oncol 30, 2012 (suppl; abstr 2526)
Heery CR, Madan RA, Stein MN, Stadler WM, Di Paola RS, Rauckhorst M, Steinberg SM, Marte JL, Chen CC, Grenga I, Donahue RN, Jochems C, Dahut WL, Schlom J, Gulley JL. Samarium-153-EDTMP (Quadramet(R)) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial. Oncotarget. 2016 Oct 18;7(42):69014-69023. doi: 10.18632/oncotarget.10883.
PubMed 27486817
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2.5 Study of (153)Sm-EDTMP (Quadramet) With or Without a PSA/TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT00450619
- Acronym / sponsor ID
- 070106
- Conditions
- Prostate Cancer
- Keywords
- Radionuclide, Immunotherapy, Radiation, PSA, Hormone Refractory Prostate Cancer, Prostate Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 22 Mar 2007 (estimated)
- Results
- Posted 1 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy.
- An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The vaccine can trigger the immune system to make cells that may be able to recognize and attack the cancer cells that make PSA.
- Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is usually given to increase a patient's white blood cell count or to stimulate the immune system.
- 1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive drug that has been approved for many years to treat advanced prostate cancer. It is given through a vein and can be targeted directly to tumors in the bone where it can relieve pain caused by bone lesions. Radiation also increases the level of certain proteins inside the tumor, making it easier for the immune system to find and kill the tumor cells.
- When laboratory mice were given just vaccine, just radiation, or a combination of both, the combination was most effective in treating tumors.
Objectives:
-To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can delay progression of prostate cancer better than radiation alone.
Eligibility:
-Patients who have advanced prostate cancer that has worsened despite treatments with hormones, have two or more bone lesions related to their prostate cancer, and have had prior treatment with docetaxel chemotherapy.
Design:
- Patients are randomly assigned to receive radiation alone (Arm A) or radiation with vaccine and sargramostim (Arm B).
- Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12 weeks.
- Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given as injections under the skin, usually in the thigh. Radiation therapy is given through a vein.
- Patients are monitored regularly with physical examinations, blood and urine tests, and scans to evaluate safety and treatment response.
- Patients who are human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for obtaining immune cells called lymphocytes to measure the immune response to the vaccine.
Detailed description
Background
- There are no standard therapy options shown to prolong survival for patients with progressive disease on first-line docetaxel-based regimens for men with metastatic castration resistant prostate cancer (CRPC).
- Ninety percent of men in this population have bone metastasis.
- PSA/TRICOM vaccines as single agents can induce generation of PSA-specific T cells in the majority of patients and objective responses and PSA declines in a minority of patients. Furthermore, the generation of at least a 6-fold increase in PSA-specific T cells was significantly correlated with evidence of clinical benefit.
- Radiation can alter the phenotype of tumor cells (increase Fas, increase major histocompatibility complex (MHC), increase tumor-associated molecules and increase ICAM), making them much more amenable to immune-mediated killing.
- (153)Sm EDTMP is a beta emitter (with some gamma emissions) that targets osteoblastic bone lesions (such as those found in prostate cancer).
- (153)Sm EDTMP, at Food And Drug Administration (FDA)-approved doses used clinically for palliation of prostate cancer, can cause phenotypic changes in tumor cells, leading to improved killing of those cells in a cytotoxic T-cell assay in vitro.
- The combination of vaccine and radiation greatly increases antitumor efficacy in a murine subcutaneous tumor model.
Objectives
- Primary-A comparison of progression-free survival at 4 months between Arm A (153)Sm EDTMP alone) and Arm B (153Sm EDTMP with vaccine).
- Secondary-Objective responses, PSA outcomes, immunologic responses, toxicity, palliation and overall survival.
Eligibility
- Patients with metastatic CRPC who have 2 or more bone lesions consistent with prostate cancer and who have been treated with a docetaxel-based regimen.
- Patients with symptomatic soft tissue disease or parenchymal disease will be excluded.
Design
- Randomized phase 2.5 study.
- Sixty-eight patients to be enrolled and randomized to:
- Arm A: (153)Sm-EDTMP: 1 mCi/kg intravenous (IV) over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery.
Arm B: PROSTAC-V/TRICOM (vaccinia) 2 x 10^8 plaque forming unit (pfu) subcutaneously on day 1.
- (153)Sm-EDTMP: 1 mCi/kg IV over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery. PROSTVAC-F/TRICOM (fowlpox) 1 x 10^9 pfu subcutaneously on days 15, 29, and then every 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A -EDTMP Alone | Experimental | Radiation: Samarium Sm 153 lexidronam pentasodiumPatients receive samarium Sm 153 lexidronam pentasodium 1 mCi/Kg intravenous (IV) over 1 minute on day 8. Treatment repeats every 12 weeks in the absence of disease progression or unacceptable toxicity. |
| Arm B - 153SmEDTMP with vaccine | Experimental | Radiation: Samarium Sm 153 lexidronam pentasodium, Biological: Sargramostim, Biological: Recombinant vaccinia-TRICOM vaccine, Biological: Recombinant fowlpox-TRICOM vaccinePatients receive recombinant vaccinia-TRICOM vaccine 2 x 10^8 PFU subcutaneously (SC) on day 1. Patients also receive recombinant fowlpox-TRICOM vaccine 1 x 10^9 PFU SC on days 15 and 29 and sargramostim (GM-CSF)100 mcg/injection SC x 4 days. Treatment with recombinant fowlpox-TRICOM vaccine and GM-CSF* repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive samarium Sm 153 lexidronam pentasodium 1 mCi/Kg as in arm I. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, National Institutes of Health (NIH), the National Naval Medical Center, or Walter Reed Army Medical Center; or participating Institute's Department of Pathology prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Must have metastatic castration resistant prostate cancer (CRPC) with at least 2 bone lesions consistent with prostate cancer metastasis and progressive disease (2 rising PSA values separated by at least one week, new or enlarging lesions consistent with prostate cancer, or clinical progression) on docetaxel for metastatic prostate cancer or inability to tolerate docetaxel.
- Life expectancy greater than or equal to 6 months.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
Key exclusion criteria (21 listed)
- Patients should have no evidence, as listed below, of being immunocompromised:
- Human immunodeficiency virus (HIV) positivity due to the potential for decreased tolerance and risk for severe side effects.
- Hepatitis B or C positivity.
- Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. This is to avoid immunosuppression which may lead to potential complications with vaccinia (priming vaccination). Nasal or inhaled steroid use is permitted.
- Patients should have no autoimmune diseases that have required treatment, such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, or active Grave's 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 tract (GI) tract, will be 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 |
|---|---|---|
| Samarium Sm 153 lexidronam pentasodium1 mCi/Kg given intravenous (IV)over 1 minute on day 8. | Radiation | Arm A -EDTMP Alone, Arm B - 153SmEDTMP with vaccine |
| Sargramostim100 mcg/injection x 4 days given subcutaneously | Biological | Arm B - 153SmEDTMP with vaccine |
| Recombinant vaccinia-TRICOM vaccine2 x 10^8 PFU given subcutaneously on day 1. | Biological | Arm B - 153SmEDTMP with vaccine |
| Recombinant fowlpox-TRICOM vaccine1 x 10^9 PFU given subcutaneously on days 15 and 29 | Biological | Arm B - 153SmEDTMP with vaccine |
Primary outcome
Number of Patients With Stable Disease at 4 Months.
Time frame: 4.7 months
Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started. Partial response (PR) is at least a 30% increase in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions on computed tomography (CT) or two or more lesions on bone scan.
Progression Free Survival (PFS)
Time frame: 4 months
PFS is defined as the time to progress or die after the start of the therapy.
9 secondary outcomes
Toxicity
Time frame: 5 years, 5 months
Number of Participants With Prostate-Specific Antigen (PSA) ≥ 30%
Time frame: 4 months
Number of Participants With Prostate-Specific Antigen (PSA) ≥50%
Time frame: 4 months
Overall Survival
Time frame: From date of randomization until death or last follow up, whichever comes first, assessed up to 14 months.
Arm A: Prostate-Specific Antigen (PSA) T-cell Responses Post-vs. Pre-treatment
Time frame: Approximately 60 days
Arm B: Prostate-Specific Antigen (PSA) T-cell Responses Post-vs. Pre-treatment
Time frame: Approximately 60 days
Objective Response (Complete Response + Partial Response)
Time frame: 4 weeks
Palliation: Pain at Baseline
Time frame: Baseline
Palliation: Improvement in Baseline Pain
Time frame: post quadramet (samarium)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1720321Turner JH, Claringbold PG. A phase II study of treatment of painful multifocal skeletal metastases with single and repeated dose samarium-153 ethylenediaminetetramethylene phosphonate. Eur J Cancer. 1991;27(9):1084-6. doi: 10.1016/0277-5379(91)90297-q.
- Background: PubMed 11251017Simon RM, Steinberg SM, Hamilton M, Hildesheim A, Khleif S, Kwak LW, Mackall CL, Schlom J, Topalian SL, Berzofsky JA. Clinical trial designs for the early clinical development of therapeutic cancer vaccines. J Clin Oncol. 2001 Mar 15;19(6):1848-54. doi: 10.1200/JCO.2001.19.6.1848.
- 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.
- Results publicationChristopher Ryan Heery, Ravi A. Madan, Marijo Bilusic, Joseph W. Kim, Nishith K. Singh, Myrna Rauckhorst, Clara Chen, William L. Dahut, Walter Michael Stadler, Robert S. DiPaola, Mark N. Stein, James W. Hodge, Jeffrey Schlom, James L. Gulley; Interim analysis of a phase II randomized clinical trial of samrium-153 (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer after docetaxel. J Clin Oncol 30, 2012 (suppl; abstr 2526)
- Results publication: PubMed 27486817Heery CR, Madan RA, Stein MN, Stadler WM, Di Paola RS, Rauckhorst M, Steinberg SM, Marte JL, Chen CC, Grenga I, Donahue RN, Jochems C, Dahut WL, Schlom J, Gulley JL. Samarium-153-EDTMP (Quadramet(R)) with or without vaccine in metastatic castration-resistant prostate cancer: A randomized Phase 2 trial. Oncotarget. 2016 Oct 18;7(42):69014-69023. doi: 10.18632/oncotarget.10883.
- 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.
James L Gulley, 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 Samarium Sm 153 lexidronam pentasodium, Sargramostim and Recombinant vaccinia-TRICOM vaccine 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 21 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 4 Jan 2017. 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 1 Jul 2013). 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?
Number of Patients With Stable Disease at 4 Months. (time frame: 4.7 months). The study lists 2 primary outcomes in all. 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 NCT00450619, which also lists 5 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 4 Jan 2017.