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Clinical Trials (PDQ®)

Sequential Vaccinations in Prostate Cancer Patients

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentCompleted18 and overNCI030176
03-C-0176, NCI-03-C-0176, NCI-5911, 5911, NCT00062153, NCT00060528

Trial Description

Summary

Background:

" Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death.

" Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is PSA, due to its restricted expression on prostate cancer and normal prostatic epithelial cells.

Objectives:

" The primary objective in Stage 1 is to evaluate the clinical safety and toxicity of a prime/boost vaccine strategy: priming with rVaccinia-PSA(L155)-TRICOM (rV-PSA-(L155)-TRICOM) with subsequent monthly boosts using rFowlpox-PSA(L155)-TRICOM (rF-PSA(L155)-TRICOM).

" The primary objective in Stage 2 is to determine the impact of granulocyte-macrophage colony stimulating factor (GM-CSF) and rF-GM-CSF on the immunologic response in patients treated with these vaccines.

" Secondary (both Stage 1 and Stage 2)-to determine the change in PSA-specific T cells in patients treated with these vaccines using ELISPOT assay analysis.

" To document any objective anti-tumor responses that may occur.

Eligibility:

" Patients must have androgen insensitive metastatic prostate cancer.

" All patients will have received and progressed on hormonal therapy.

" Must have objective evidence of metastasis or relapsing local disease. Therefore, must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies.

" Must have a life expectancy of more than 6 months and ECOG status of 0 to 2.

" For Stage 2 of this study, patients must be HLA-A2+.

" Granulocyte count greater than or equal to 1,500/mm(3), Platelet greater than or equal to 100,000/mm(3), Hgb greater than or equal to 10Gm/dL, Lymphocyte count greater than or equal to 500/mm(3) ;Bilirubin less than 1.5mg/dL, AST and ALT less than 2.5xULN,CreatinineClearance greater than or equal to 60

" No significant cardiac disease, no significant pulmonary disease, no serious inter-current medical illness.

Design:

" This study will utilize a dose escalation Phase I design. Stage 1 will consist of five cohorts as shown in the schema.

" The first cohort utilizes a fixed dose of rF-PSA (L155)-TRICOM alone, while the second cohort will test the safety of rV-PSA(L155)-TRICOM as a priming vaccination followed by monthly boosting with rF-PSA (L155)-TRICOM.

" Cohorts three, four and five will provide safety data combini...

Further Study Information

Background:

  • Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death.
  • Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is PSA, due to its restricted expression on prostate cancer and normal prostatic epithelial cells.

Objectives:

  • The primary objective in Stage 1 is to evaluate the clinical safety and toxicity of a prime/boost vaccine strategy: priming with rVaccinia-PSA(L155)-TRICOM (rV-PSA-(L155)-TRICOM) with subsequent monthly boosts using rFowlpox-PSA(L155)-TRICOM (rF-PSA(L155)-TRICOM).
  • The primary objective in Stage 2 is to determine the impact of granulocyte-macrophage colony stimulating factor (GM-CSF) and rF-GM-CSF on the immunologic response in patients treated with these vaccines.
  • Secondary (both Stage 1 and Stage 2)-to determine the change in PSA-specific T cells in patients treated with these vaccines using ELISPOT assay analysis.
  • To document any objective anti-tumor responses that may occur.

Eligibility:

  • Patients must have androgen insensitive metastatic prostate cancer.
  • All patients will have received and progressed on hormonal therapy.
  • Must have objective evidence of metastasis or relapsing local disease. Therefore, must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies.
  • Must have a life expectancy of more than 6 months and ECOG status of 0 to 2.
  • For Stage 2 of this study, patients must be HLA-A2+.
  • Granulocyte count greater than or equal to 1,500/mm(3), Platelet greater than or equal to 100,000/mm(3), Hgb greater than or equal to 10Gm/dL, Lymphocyte count greater than or equal to 500/mm(3) ;Bilirubin less than 1.5mg/dL, AST and ALT less than 2.5xULN,CreatinineClearance greater than or equal to 60
  • No significant cardiac disease, no significant pulmonary disease, no serious inter-current medical illness.

Design:

  • This study will utilize a dose escalation Phase I design. Stage 1 will consist of five cohorts as shown in the schema.
  • The first cohort utilizes a fixed dose of rF-PSA (L155)-TRICOM alone, while the second cohort will test the safety of rV-PSA(L155)-TRICOM as a priming vaccination followed by monthly boosting with rF-PSA (L155)-TRICOM.
  • Cohorts three, four and five will provide safety data combining cohort two with rGM-CSF as well as two doses of rFGM-CSF respectively. The maximal tolerated dose (MTD) established in Stage 1 (cohorts 2-5) of this trial will be used in Stage 2 of the protocol.
  • Stage 2 will be conducted as a small, randomized pilot study to compare the immunologic effects of the above vaccine strategy alone, with recombinant GM-CSF, or with either of 2 doses of fowlpox-GM-CSF.
  • Stage 2 will consist of 4 randomized arms of 8 patients each, all of whom are HLA-A2+.

The maximum accrual to the trial should be 62: up to 30 patients in Stage 1 (5 cohorts of up to 6 patients), and 32 patients in Stage 2 (4 arms of 8 patients apiece).

Eligibility Criteria

  • INCLUSION CRITERIA: Stage 1 Patients

Patients must have histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, CCR, NCI, or NNMC prior to starting this study. If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

Patients must have androgen insensitive metastatic prostate cancer. Progression must be documented by at least one of the following parameters.

1. All patients must have received standard of care (hormonal) treatment before entering the trial.

2. All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.

3. All subjects must have objective evidence of metastasis or relapsing local disease to be eligible for this Phase I trial; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.

i. Two consecutively rising PSA levels, separated by at least 1 week, with at least one measurement that is 50% above the

nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and

ii. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or

iii. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).

Patients must have a life expectancy of more than 6 months.

Patients must have a performance status of 0 to 2 according to the ECOG criteria.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study). Patients who are responding to hormonal therapy are not eligible until evidence of disease progression.

Hematological eligibility parameters (within 16 days of starting therapy):

  • Granulocyte count greater than or equal to 1,500/mm3
  • Platelet count greater than or equal to 100,000/mm3
  • Lymphocyte count greater than or equal to 500/mm3
  • Hgb greater than or equal to10 Gm/dL

Biochemical eligibility parameters (within 16 days of starting therapy):

1. A 24-hour urine collection for baseline to measure creatinine clearance, protein and electrolytes. CrCl greater than 60, proteinuria less than 1000 milligrams per 24 hours, less than or equal to Grade 1 (NCI-CTC version 2.0) proteinuria, Grade 0 hematuria, and no abnormal sediment. Grade 0 creatinine. Patients must have serum creatinine within normal limits.

Any abnormalities in the sediment or the presence of hematuria without a likely underlying cause should prompt the investigator to consider an evaluation by a nephrologist for evidence of underlying renal pathology. Patients may be eligible if the underlying cause of the abnormality is determined to be non-renal.

2. Hepatic function: Bilirubin less than 1.5 mg/dl, AST and ALT less than 2.5 times upper limit of normal.

3. Patients must be test negative for HIV, Hepatitis B and C.

Patients must not have other active malignancies within the past 2 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.

Patients must be willing to travel to the NIH for follow-up visits.

Patients must be greater than or equal to 18 years of age.

All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of allergy or untoward reaction to the vaccine. Since vaccinia immunoglobulin (VIG) is available from the CDC, prior vaccinia vaccination as a safety precaution is no longer required.

Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.

For Stage 2 of this study only, patients must not have received the following chemotherapeutic agents for cancer within 3 years of enrolling on study: docetaxel, paclitaxel, doxorubicin, cisplatinum, carboplatinum, mitoxantrone, estramustine, cyclophosphamide, irinotecan, topotecan. Patients must not have received prior PSA vaccine therapy.

Patients will tested for HLA-A2; however, the results of this test will not affect entry onto Stage 1 of this study. This test may be drawn by the patient's referring physician at the time of referral (see Appendix C, HLA-typing consent). This consent will be mailed to the patient and discussed with patient. The signed consent will be signed with a witness, then mailed to the assigned research nurse at the NIH Clinical Center. These patients must have measurable disease on CT, MRI, or bone scan.

The effects of the study agents used in this protocol on the developing human fetus are unknown. For this reason men must agree to use adequate contraception prior to study entry and for the duration of study participation.

INCLUSION CRITERIA: Stage 2 Patients

Patients must have histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, CCR, NCI, or NNMC prior to starting this study. If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.

Patients must have androgen insensitive metastatic prostate cancer. Progression must be documented by at least one of the following parameters.

1. All patients must have received standard of care (hormonal) treatment before entering the trial.

2. All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.

3. All subjects must have objective evidence of metastasis or relapsing local disease to be eligible for this Phase I trial; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.

i. Two consecutively rising PSA levels, separated by at least 1 week, with at least one measurement that is 50% above the

nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and

ii. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or

iii. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).

Patients must have a life expectancy of more than 6 months.

Patients must have a performance status of 0 to 2 according to the ECOG criteria.

Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study).

Hematological eligibility parameters (within 16 days of starting therapy):

  • Granulocyte count greater than or equal to1,500/mm3
  • Platelet count greater than or equal to 100,000/mm3
  • Lymphocyte count greater than or equal to 500/mm3
  • Hgb greater than or equal to 10 Gm/dL

Biochemical eligibility parameters (within 16 days of starting therapy):

1. A 24-hour urine collection for baseline to measure creatinine clearance, protein and electrolytes. CrCl greater than 60, proteinuria less than 1000 milligrams per 24 hours, less than or equal to Grade 1 (NCI-CTC version 2.0) proteinuria, Grade 0 hematuria, and no abnormal sediment. Grade 0 creatinine. Patients must have serum creatinine within normal limits.

Any abnormalities in the sediment or the presence of hematuria without a likely underlying cause should prompt the investigator to consider an evaluation by a nephrologist for evidence of underlying renal pathology. Patients may be eligible if the underlying cause of the abnormality is determined to be non-renal.

2. Hepatic function: Bilirubin less than 1.5 mg/dl, AST and ALT less than 2.5 times upper limit of normal.

3. Patients must test negative for HIV, Hepatitis B and C.

Patients must not have other active malignancies within the past 2 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.

Patients must be willing to travel to the NIH for follow-up visits.

Patients must be greater than or equal to 18 years of age.

All patients who have received prior vaccination with vaccinia virus (for smallpox immunization) must not have a history of allergy or untoward reaction to the vaccine. Since vaccinia immunoglobulin (VIG) is available from the CDC, prior vaccinia vaccination as a safety precaution is no longer required.

Patients must understand and sign informed consent that explains the neoplastic nature of their disease, the procedures to be followed, the experimental nature of the treatment, alternative treatments, potential risks and toxicities, and the voluntary nature of participation.

For Stage 2 of this study only, patients have not received the following chemotherapeutic agents for cancer within 3 years of enrolling on study: docetaxel, paclitaxel, doxorubicin, cisplatinum, carboplatinum, mitoxantrone, estramustine, cyclophosphamide, irinotecan, topotecan. Patients have not received prior PSA vaccine therapy.

All patients will tested for HLA-A2; however, for Stage 2 of this study patients must be HLA-A2+. This test may be drawn by the patient's referring physician at the time of referral (see Appendix C, HLA-typing consent). This consent will be mailed to the patient and discussed with patient. The signed consent will be signed with a witness, then mailed to the assigned research nurse at the NIH Clinical Center. These patients must have measurable disease on CT, MRI, or bone scan.

The effects of the study agents used in this protocol on the developing human fetus are unknown. For this reason men must agree to use adequate contraception prior to study entry and for the duration of study participation.

EXCLUSION CRITERIA: Stage 1 Patients

Prior splenectomy.

Concurrent steroid use, except topical steroids or inhaled steroid use.

The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts: 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 under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection. Close household contacts are those who share housing or have close physical contact.

Patients with known allergy to eggs.

Other serious intercurrent illness.

Patients with brain metastases.

Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II-IV congestive heart failure.

Patients on antiandrogen therapy must undergo antiandrogen 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.

Patients with significant autoimmune disease that is active or potentially life threatening if activated.

Patients with clinically significant cardiomyopathy requiring treatment should be excluded from protocol eligibility at this time.

EXCLUSION CRITERIA: Stage 2 Patients

Prior splenectomy.

Concurrent steroid use, except topical steroids or inhaled steroid use.

The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts: 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 under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection. Close household contacts are those who share housing or have close physical contact.

Patients with known allergy to eggs.

Other serious intercurrent illness.

Patients with brain metastases.

Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II-IV congestive heart failure.

Patients on antiandrogen therapy must undergo antiandrogen 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.

For Stage 2 patients only, prior treatments with vaccine expressing PSA are NOT eligible.

Patients with significant autoimmune disease that is active or potentially life threatening if activated.

Patients with clinically significant cardiomyopathy requiring treatment should be excluded from protocol eligibility at this time.

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00060528
Information obtained from ClinicalTrials.gov on July 25, 2010

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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