153Sm-EDTMP With or Without a PSA/TRICOM Vaccine To Treat Men With Androgen-Insensitive Prostate Cancer

NCT00450619 | Completed Phase 2 Results DMC

• 2 other identifiers: 07010607-C-0106
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 3

Brief 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 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.

Conditions

Prostate Cancer

Keywords

Radionuclide; Immunotherapy; Radiation; PSA; Hormone Refractory Prostate Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  4.7 months

• Progression Free Survival (PFS)

  PFS is defined as the time to progress or die after the start of the therapy.

  4 months

Secondary Outcomes (9)

• Toxicity

  5 years, 5 months

• Number of Participants With Prostate-Specific Antigen (PSA) ≥ 30%

  4 months

• Number of Participants With Prostate-Specific Antigen (PSA) ≥50%

  4 months

• Overall Survival

  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

  Approximately 60 days

Study Arms (2)

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.

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.

Radiation: Samarium Sm 153 lexidronam pentasodium; Biological: Sargramostim; Biological: Recombinant vaccinia-TRICOM vaccine; Biological: Recombinant fowlpox-TRICOM vaccine

Interventions

Samarium Sm 153 lexidronam pentasodium RADIATION

1 mCi/Kg given intravenous (IV)over 1 minute on day 8.

Arm A -EDTMP Alone; Arm B - 153SmEDTMP with vaccine

Sargramostim BIOLOGICAL

100 mcg/injection x 4 days given subcutaneously

Arm B - 153SmEDTMP with vaccine

Recombinant vaccinia-TRICOM vaccine BIOLOGICAL

2 x 10\^8 PFU given subcutaneously on day 1.

Arm B - 153SmEDTMP with vaccine

Recombinant fowlpox-TRICOM vaccine BIOLOGICAL

1 x 10\^9 PFU given subcutaneously on days 15 and 29

Arm B - 153SmEDTMP with vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. 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.
• B. 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.
• C. Life expectancy greater than or equal to 6 months.
• D. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
• F. Hematological eligibility parameters (within 16 days of starting therapy).
• 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)
• G. 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.
• H. 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.
• I. Willing to travel to the National Institutes of Health (NIH) or participating Institute for follow-up visits.
• J. 18 years of age or greater.
• K. Able to understand and sign informed consent.

You may not qualify if:

• A. 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.
• B. 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.
• C. 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.
• D. 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.
• E. 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.
• F. 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.
• G. 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.
• H. 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.
• I. Patients with pulmonary disease who have fatigue or dyspnea with ordinary physical activity are not eligible.
• J. Concurrent chemotherapy.
• K. No brain metastasis or history of seizures, encephalitis, or multiple sclerosis.
• L. Serious hypersensitivity reaction to egg products.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

University of Chicago

Chicago, Illinois, 60637, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Related Publications (5)

• 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.

  PMID: 1720321 BACKGROUND

• Simon 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.

  PMID: 11251017 BACKGROUND

• Therasse 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.

  PMID: 10655437 BACKGROUND

• Christopher 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)

  RESULT

• 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.

  PMID: 27486817 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

samarium Sm-153 lexidronam; sargramostim; rV-Tricom

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

This study was stopped before full accrual(after about two-thirds of the subjects were enrolled) due to a significant decrease in enrollment despite making this a multicenter study.

Results Point of Contact

• Title: Dr. James Gulley, M.D.
• Organization: National Cancer Institute, National Institutes of Health

gulleyj@mail.nih.gov

301-435-2956

Study Officials

• James L Gulley, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: February 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: January 4, 2017
• Results First Posted: July 1, 2013

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)