Prostate Cancer
Conditions
Keywords
Tecemotide, Prostate Cancer, Goserelin, Cyclophosphamide, Radiotherapy
Brief summary
This study examines tecemotide (L-BLP25) in combination with standard treatment for prostate cancer.
Interventions
RADIATIONRadiation therapy
Radiation therapy will be administered at a daily dose of 180 centigrays (cGy) 5 days a week for approximately 6 to 8 weeks.
DRUGGoserelin
ADT (Goserelin) will be administered at a dose of 10.8 milligrams (mg) subcutaneously every 3 months for 24 months for the high risk group and for 6 months in the intermediate risk group, starting 2-3 months prior to radiation therapy.
DRUGCyclophosphamide
Cyclophosphamide will be administered at a single dose of 300 milligrams per square meter (mg/m\^2) to a maximum of 600 mg, as an intravenous injection 3 days prior to the first administration of tecemotide (L-BLP25).
Tecemotide (L-BLP25) will be administered at a dose of 918 microgram (mcg) as subcutaneous injection every 2 weeks for 5 doses followed by every 6 weeks for an additional 4 doses, starting 2-3 months prior to radiation therapy and on the same day that ADT began.
Sponsors
National Cancer Institute (NCI)
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histopathologic documentation of prostate cancer confirmed at the institution of study enrollment prior to starting this study * Newly diagnosed or previously untreated prostate cancer with intermediate or high risk features as defined in the protocol * No evidence of metastatic disease on computed tomography (CT) / magnetic resonance imaging (MRI) or bone scans * No systemic steroid use within 2 weeks prior to initiation of experimental therapy. Limited doses of systemic steroids to prevent intravenous contrast, allergic reaction or anaphylaxis (in subjects who have known contrast allergies) are allowed * Eastern Co-operative Oncology Group (ECOG) performance status of 0-1 * Human leukocyte antigen (HLA)-A2 or A3 positive for immunologic monitoring * Hematological and biochemical eligibility parameters as defined in the protocol * No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) * Willing to travel to the study center(s) for follow-up visits * Age greater than or equal to 18 years old * 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 administration of immunotherapy
Exclusion criteria
* No evidence of being immunocompromised by human immunodeficiency virus, a medical condition requiring systemic steroids, a medical condition requiring immunosuppressive therapy, splenectomy * Active Hepatitis B or Hepatitis C * Subjects should have no autoimmune diseases that have required treatment as specified in the protocol * History of immunodeficiency diseases, hereditary or congenital immunodeficiencies * Serious intercurrent medical illness * A clinically significant cardiac disease * Subjects who have received any prior therapy for prostate cancer * Subjects who have known brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis * Subjects receiving any other investigational agents * Contraindication to biopsy such as bleeding disorders, ratio of prothrombin time to partial thromboplastin time (PT/PTT) \>=1.5 times the upper limit of normal, artificial heart valve * Contraindication to MRI such as subjects weighing \>136 kilograms, allergy to magnetic resonance (MR) contrast agent, subjects with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices * Contraindication to radiation therapy such as pre-existing and active prostatitis or proctitis, inflammatory bowel disease or known genetic sensitivity to ionizing radiation, or history of prior radiation to the pelvis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 60 (Pre-Radiation) | Baseline and Day 60 (Pre-Radiation) | MUC1-specific systemic immune response was measured by intracellular cytokine antigen specific staining following a period of in vitro stimulation (IVS) with overlapping 15-mer peptide pools encoding the tumor-associated antigen (TAA) MUC-1. Baseline was defined as the measurement taken prior to the first dose of study medication (Day 1). |
| Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 190 (Post-radiation) | Baseline and Day 190 (Post-radiation) | MUC1-specific systemic immune response was measured by intracellular cytokine antigen specific staining following a period of in vitro stimulation (IVS) with overlapping 15-mer peptide pools encoding the tumor-associated antigen (TAA) MUC-1. Baseline was defined as the measurement taken prior to the first dose of study medication (Day 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Progression/Recurrence Status Based on Prostate-specific Antigen (PSA) Levels | From randomization up to 24 months | Progression/recurrence status was reported based on Prostate-specific Antigen (PSA) Levels. Recurrence of PSA after completion of therapy represents disease progression and was determined using the American Society for Therapeutic Radiology and Oncology (ASTRO) Phoenix criteria. These criteria define biochemical recurrence after radiation therapy as a PSA level equal to the lowest (nadir) PSA level achieved after therapy plus 2 nanogram per milliliter. |
| Number of Subjects With a Doubling in Number of T-cells in Tumor Biopsy From Baseline at Pre-radiotherapy (Pre-RT) and Post-radiotherapy (Post-RT) | Baseline, Week 6-12 (Pre-RT), Week 40 (Post-RT) | Doubling in number of T-cells was assessed by immunologic responses (in the tumor microenvironment) in subjects consenting to undergo study biopsies. Baseline was defined as the measurement taken within 8 weeks of prior to the first dose of study medication (Day 1). |
Countries
United States
Participant flow
Recruitment details
First subject First Visit/Last Subject Last Visit: 24 October 2011/25 November 2016.
Participants by arm
| Arm | Count |
|---|---|
| Standard Therapy Subjects received Goserelin 10.8 milligrams (mg) subcutaneously every 3 months for 2 years and radiation therapy lasting 6-8 weeks starting 2-3 months after ADT. | 14 |
| Standard Therapy Subjects received Goserelin 10.8 milligrams (mg) subcutaneously every 3 months for 2 years and radiation therapy lasting 6-8 weeks starting 2-3 months after ADT. | 14 |
| Standard Therapy Plus Tecemotide (L-BLP25) Subjects received Goserelin 10.8 mg subcutaneously every 3 months for 2 years and radiation therapy lasting 6-8 weeks starting 2-3 months after ADT. In addition to the above standard treatment, subjects received tecemotide at a dose of 918 microgram (mcg) as subcutaneous injections every 2 weeks for 2 months followed by continuation treatment with 4 doses of tecemotide every 6 weeks. Subjects also received a single dose of cyclophosphamide 300 mg per square meter intra-venously 3 days before 1st administration of tecemotide. | 14 |
| Standard Therapy Plus Tecemotide (L-BLP25) Subjects received Goserelin 10.8 mg subcutaneously every 3 months for 2 years and radiation therapy lasting 6-8 weeks starting 2-3 months after ADT. In addition to the above standard treatment, subjects received tecemotide at a dose of 918 microgram (mcg) as subcutaneous injections every 2 weeks for 2 months followed by continuation treatment with 4 doses of tecemotide every 6 weeks. Subjects also received a single dose of cyclophosphamide 300 mg per square meter intra-venously 3 days before 1st administration of tecemotide. | 14 |
| Total | 56 |
Baseline characteristics
| Characteristic | Standard Therapy | Standard Therapy Plus Tecemotide (L-BLP25) | Total |
|---|---|---|---|
| Age, Continuous | 69.0 years | 64 years | 64.5 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 14 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 14 / 14 | 14 / 14 |
| serious Total, serious adverse events | 1 / 14 | 2 / 14 |
Outcome results
Primary
Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 190 (Post-radiation)
MUC1-specific systemic immune response was measured by intracellular cytokine antigen specific staining following a period of in vitro stimulation (IVS) with overlapping 15-mer peptide pools encoding the tumor-associated antigen (TAA) MUC-1. Baseline was defined as the measurement taken prior to the first dose of study medication (Day 1).
Time frame: Baseline and Day 190 (Post-radiation)
Population: Analysis population included only subjects who had scored positive to viral pool in peripheral blood mononuclear cells and were considered as evaluable. Here, Number of Participants Analyzed signifies subjects evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Therapy | Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 190 (Post-radiation) | 1 Participants |
| Standard Therapy Plus Tecemotide (L-BLP25) | Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 190 (Post-radiation) | 1 Participants |
Primary
Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 60 (Pre-Radiation)
MUC1-specific systemic immune response was measured by intracellular cytokine antigen specific staining following a period of in vitro stimulation (IVS) with overlapping 15-mer peptide pools encoding the tumor-associated antigen (TAA) MUC-1. Baseline was defined as the measurement taken prior to the first dose of study medication (Day 1).
Time frame: Baseline and Day 60 (Pre-Radiation)
Population: Analysis population included only subjects who had scored positive to viral pool in peripheral blood mononuclear cells and were considered as evaluable. Here, Number of Participants Analyzed signifies subjects evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Therapy | Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 60 (Pre-Radiation) | 2 Participants |
| Standard Therapy Plus Tecemotide (L-BLP25) | Number of Subjects With Change From Baseline in the Mucinous Glycoprotein 1 (MUC1) Specific Systemic T-Cells Immune Response at Day 60 (Pre-Radiation) | 3 Participants |
Secondary
Number of Subjects With a Doubling in Number of T-cells in Tumor Biopsy From Baseline at Pre-radiotherapy (Pre-RT) and Post-radiotherapy (Post-RT)
Doubling in number of T-cells was assessed by immunologic responses (in the tumor microenvironment) in subjects consenting to undergo study biopsies. Baseline was defined as the measurement taken within 8 weeks of prior to the first dose of study medication (Day 1).
Time frame: Baseline, Week 6-12 (Pre-RT), Week 40 (Post-RT)
Population: Analysis population included only the subjects who were randomized and provided consent for biopsy and whose baseline measurement was considered as evaluable. Here, number analyzed signifies subjects evaluable at specified time point and number analyzed=0 signifies that no subjects were evaluable at the specified time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Standard Therapy | Number of Subjects With a Doubling in Number of T-cells in Tumor Biopsy From Baseline at Pre-radiotherapy (Pre-RT) and Post-radiotherapy (Post-RT) | Pre-RT | 1 Participants |
| Standard Therapy Plus Tecemotide (L-BLP25) | Number of Subjects With a Doubling in Number of T-cells in Tumor Biopsy From Baseline at Pre-radiotherapy (Pre-RT) and Post-radiotherapy (Post-RT) | Pre-RT | 1 Participants |
| Standard Therapy Plus Tecemotide (L-BLP25) | Number of Subjects With a Doubling in Number of T-cells in Tumor Biopsy From Baseline at Pre-radiotherapy (Pre-RT) and Post-radiotherapy (Post-RT) | Post-RT | 1 Participants |
Secondary
Number of Subjects With Progression/Recurrence Status Based on Prostate-specific Antigen (PSA) Levels
Progression/recurrence status was reported based on Prostate-specific Antigen (PSA) Levels. Recurrence of PSA after completion of therapy represents disease progression and was determined using the American Society for Therapeutic Radiology and Oncology (ASTRO) Phoenix criteria. These criteria define biochemical recurrence after radiation therapy as a PSA level equal to the lowest (nadir) PSA level achieved after therapy plus 2 nanogram per milliliter.
Time frame: From randomization up to 24 months
Population: Analysis population included all subjects randomized in the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Therapy | Number of Subjects With Progression/Recurrence Status Based on Prostate-specific Antigen (PSA) Levels | 2 Participants |
| Standard Therapy Plus Tecemotide (L-BLP25) | Number of Subjects With Progression/Recurrence Status Based on Prostate-specific Antigen (PSA) Levels | 0 Participants |