Prostate Cancer
Conditions
Keywords
Prostate Cancer, MRI, Fiducial Marker, IMRT
Brief summary
BACKGROUND: -This study represents a progression from findings in four previous National Cancer Institute (NCI) Radiation Oncology Branch (ROB) protocols (02-C-0167A, 02-C-0207E, 03-C-0190B, 04-C-0171). In these previous works we have begun to develop techniques to obtain magnetic resonance (MR) biological images and co-register tissue in prostate cancer patients. OBJECTIVES: -The scientific objective of this protocol is to determine the maximum tolerated dose (MTD) of external beam radiation to regions of interest within the prostate based acute toxicity. Secondary objectives of this study are to relate patterns in gene and protein expression to response and toxicity and to evaluate the frequency of late term toxicity. ELIGIBILITY: -Patients with prostate cancer without evidence of metastasis will be eligible for this study. DESIGN: * This phase I trial will use intensity modulated radiation therapy (IMRT) to deliver escalating doses of external beam radiation to regions of histologically confirmed prostate cancer. The study will be conducted using a standard 3-6 dose-escalation with an initial 3 patients in each dose cohort and the potential expansion of the cohort to 6 patients. * Anatomic magnetic resonance imaging (MRI) and magnetic resonance (MR) biological images, such as magnetic resonance spectroscopy (MRS), will be obtained. Tissue will be acquired from sites of interest, with biopsy locations precisely translated (co-registered) to an MR image of reference. Tissue samples will be processed for complementary deoxyribonucleic acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology Branch, NCI. A gold seed will be left at the biopsy site as a fiducial marker to direct future radiation therapy. If necessary, additional fiducial markers will be placed for target localization during treatment. * Once MR guided biopsies are obtained and fiducial markers placed, the patient will undergo a standard computed tomography (CT) simulation for radiation therapy treatment planning. The MR and CT images will be fused. Areas of pathologically confirmed malignancy will undergo dose escalation as described below. Areas of image abnormality that could not be biopsied or were without definite pathologic evidence of malignancy will be given intermediate doses. The remainder of the prostate gland will receive standard dose (7560 centigray (cGy)'). * The trial will accrue 18 to 36 patients with an anticipated accrual period of 2 years.
Detailed description
BACKGROUND: -This study represents a progression from findings in four previous National Cancer Institute (NCI) Radiation Oncology Branch (RO)B protocols (02-C-0167A, 02-C-0207E, 03-C-0190B, 04-C-0171). In these previous works we have begun to develop techniques to obtain magnetic resonance (MR) biological images and co-register tissue in prostate cancer patients. OBJECTIVES: * The scientific objective of this protocol is to determine the maximum tolerated dose (MTD) of external beam radiation to regions of interest within the prostate based acute toxicity. * Secondary objectives of this study are to relate patterns in gene and protein expression to response and toxicity and to evaluate the frequency of late term toxicity. ELIGIBILITY: -Patients with prostate cancer without evidence of metastasis will be eligible for this study. DESIGN: * This phase I trial will use intensity modulated radiation therapy (IMRT) to deliver escalating doses of external beam radiation to regions of histologically confirmed prostate cancer. The study will be conducted using a standard 3-6 dose-escalation with an initial 3 patients in each dose cohort and the potential expansion of the cohort to 6 patients. * Anatomic magnetic resonance imaging (MRI) and MR biological images, such as magnetic resonance spectroscopy (MRS), will be obtained Tissue will be acquired from sites of interest, with biopsy locations precisely translated (co-registered) to an MR image of reference. Tissue samples will be processed for complementary deoxyribonucleic acid (cDNA) microarray testing and stored for future analysis in the Radiation Oncology Branch, NCI. A gold seed will be left at the biopsy site as a fiducial marker to direct future radiation therapy. If necessary, additional fiducial markers will be placed for target localization during treatment. * Once MR guided biopsies are obtained and fiducial markers placed, the patient will undergo a standard computed tomography (CT) simulation for radiation therapy treatment planning. The MR and CT images will be fused. Areas of pathologically confirmed malignancy will undergo dose escalation as described below. Areas of image abnormality that could not be biopsied or were without definite pathologic evidence of malignancy will be given intermediate doses. The remainder of the prostate gland will receive standard dose (7560 centigray (cGy)). * The trial will accrue 18 to 36 patients with an anticipated accrual period of 2 years.
Interventions
RADIATIONRadiation
Areas of pathologically confirmed malignancy will undergo dose escalation as described below. Areas of image abnormality that could not be biopsied or were without definite pathologic evidence of malignancy will be given intermediate doses. The remainder of the prostate gland will receive standard dose (as per the Radiation Therapy Oncology Group (RTOG) 9406 study) 7560 centigray (cGy) in 180 cGy daily fractions.\[1\]
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: 1. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 2. Pathology report confirming adenocarcinoma of the prostate 3. Risk of lymph node metastasis less than 10% as defined by the Partin tables 4. Tumor visible on magnetic resonance imaging (MRI) 5. No prior surgery, radiation, or chemotherapy for prostate cancer. 6. Age greater than 18 y/o and less than 90 years old.
Exclusion criteria
1. Cognitively impaired patients who cannot give informed consent. 2. Patients with metastatic disease. 3. Contraindication to biopsy * Bleeding disorder * Prothrombin time (PT)/Partial Thromboplastin Time (PTT) greater than or equal to 1.5 times the upper limit of normal * Platelets less than or equal to 50K * Artificial heart valve 4. Contraindication to magnetic resonance imaging (MRI) * Patients weighing greater than 136 kgs (weight limit for the scanner tables) * Allergy to MR contrast agent * Patients with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices. 5. Pre-existing and active prostatitis or proctitis 6. Other medical conditions deemed by the principal investigator (PI) or associates to make the patient ineligible for protocol investigations, procedures, and high-dose external beam radiotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of External Beam Radiation | 12 weeks after radiation therapy (RT) | Maximum tolerated dose is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experienced a dose limiting toxicity attributed to radiation therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and Non-serious Adverse Events | 53 months and 20 days | Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTC v3.0). 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Radiation Response With Genomic and Proteomic Analyses | completion of therapy | Genomic and proteomic analyses will be conducted on a gene by gene basis using a 2-sample t-test at the 0.001 level and correlated with radiation response. |
| Correlate Toxicity With Genomic and Proteomic Analyses | Completion of therapy | Genomic and proteomic analyses will be conducted on a gene by gene basis using a 2-sample t-test at the 0.001 level and correlated with toxicity. |
| Long-term Effects and Toxicity Following Selective Intra-prostatic Dose Escalation | completion of therapy | Acute and late toxicity will be assessed by the Radiation Therapy Oncology Group (RTOG) Acute and Late Toxicity Genitourinary (GI)/Gastrointestinal (GU) scales. |
Countries
United States
Participant flow
Pre-assignment details
All 6 participants enrolled in this trial received a dose of 7560 cGy and are grouped together in one Arm/Group. An attempt was made to escalate to the next higher dose but we were unable to treat patients and maintain safety standards.
Participants by arm
| Arm | Count |
|---|---|
| Radiation Therapy - 7560 cGY Radiation to tumor area as per protocol
Radiation: Areas of pathologically confirmed malignancy will undergo dose escalation as described below. Areas of image abnormality that could not be biopsied or were without definite pathologic evidence of malignancy will be given intermediate doses. The remainder of the prostate gland will receive standard dose (as per the Radiation Therapy Oncology Group (RTOG) 9406 study) 7560 centigray (cGy) in 180 cGy daily fractions.\[1\] | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | Radiation Therapy - 7560 cGY |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 68.17 years STANDARD_DEVIATION 10.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 3 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of External Beam Radiation
Maximum tolerated dose is defined as the dose level immediately below the dose level at which 2 or more in a cohort of either 3 or 6 patients experienced a dose limiting toxicity attributed to radiation therapy.
Time frame: 12 weeks after radiation therapy (RT)
Population: This outcome measure was not done. All 6 participants enrolled in this trial received a dose of 7560 cGy and are grouped together in one Arm/Group. An attempt was made to escalate to the next higher dose but we were unable to treat patients and maintain safety standards.
Secondary
Number of Participants With Serious and Non-serious Adverse Events
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTC v3.0). 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.
Time frame: 53 months and 20 days
Population: All 6 participants enrolled in this trial received a dose of 7560 cGy and are grouped together in one Arm/Group. An attempt was made to escalate to the next higher dose but we were unable to treat patients and maintain safety standards.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiation Therapy - 7560 cGY | Number of Participants With Serious and Non-serious Adverse Events | 3 Participants |
Other Pre-specified
Correlate Toxicity With Genomic and Proteomic Analyses
Genomic and proteomic analyses will be conducted on a gene by gene basis using a 2-sample t-test at the 0.001 level and correlated with toxicity.
Time frame: Completion of therapy
Population: This outcome measure was not done because the study was closed due to unanticipated toxicity and risks to subjects.
Other Pre-specified
Long-term Effects and Toxicity Following Selective Intra-prostatic Dose Escalation
Acute and late toxicity will be assessed by the Radiation Therapy Oncology Group (RTOG) Acute and Late Toxicity Genitourinary (GI)/Gastrointestinal (GU) scales.
Time frame: completion of therapy
Population: This outcome measure was not done because the study was closed due to unanticipated toxicity and risks to subjects.
Other Pre-specified
Radiation Response With Genomic and Proteomic Analyses
Genomic and proteomic analyses will be conducted on a gene by gene basis using a 2-sample t-test at the 0.001 level and correlated with radiation response.
Time frame: completion of therapy
Population: This outcome measure was not done because the study was closed due to unanticipated toxicity and risks to subjects.