Prostate Adenocarcinoma, Stage IIC Prostate Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IIIA Prostate Cancer AJCC v8, Stage IIIB Prostate Cancer AJCC v8, Stage IIIC Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8
Conditions
Brief summary
This is a phase I-II trial to find the safety and activity of adding a new drug (neraparib) to the usual treatment (radiation combined with male hormone deprivation therapy) in lowering the chance of prostate cancer growing or returning. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Adding niraparib to the usual care may lower the chance of prostate cancer growing or returning.
Detailed description
PRIMARY OBJECTIVES: I. To establish the preferred dose of niraparib in combination with radiation and antiandrogen therapy (ADT). (Phase I) II. To compare the disease-free state, defined as prostate specific antigen (PSA) remaining \< 0.1 ng/ml at the end of ADT therapy in men with high risk prostate cancer treated with standard therapy with or without the addition of niraparib. (Phase IIR) SECONDARY OBJECTIVES: I. To further establish the safety and toxicity profile of standard treatment with radiation and androgen deprivation therapy specifically, two years from initiation of ADT, plus niraparib at the phase II dose. II. To compare the overall survival, prostate cancer-specific survival, local/regional or distant progression, and distant metastatic disease rates of standard therapy with or without the addition of niraparib. EXPLORATORY OBJECTIVE: I. To identify genomic biomarkers of response to combination therapy with radiation, ADT and PARP inhibition. OUTLINE: This is a phase I, dose-escalation study of niraparib, followed by a randomized phase II study. PHASE I: Patients receive niraparib orally (PO) once daily (QD) and receive standard of care gonadotrophin releasing hormone (GnRH) agonist androgen suppression therapy. Treatment with niraparib continues for 12 months, and GnRH agonist therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib and GnRH agonist, patients undergo standard of care intensity-modulated radiation therapy (IMRT) 5 days per week for about 6-9 weeks, depending on type of radiation therapy given, in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) on study. PHASE II: Patients are randomized to 1 of 2 arms: ARM I: Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8-28 weeks after starting GnRH agonist, patients undergo IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study. ARM II: Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study. After completion of study treatment, patients are followed up every 6 months for 3 years, then annually for 3 years.
Interventions
BIOLOGICALGonadotrophin Releasing Hormone
Receive standard of care GnRH agonist androgen suppression therapy
RADIATIONIntensity-Modulated Radiation Therapy
Undergo standard of care IMRT
DRUGNiraparib
tablet
Sponsors
NRG Oncology
National Cancer Institute (NCI)
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
* Histologically confirmed (within 180 days prior to registration) adenocarcinoma of the prostate at high risk for recurrence as determined by the following criteria, according to American Joint Committee on Cancer (AJCC) 8th edition: * Phase I enrollment * Gleason \>= 9, PSA =\< 150 ng/mL, any T-stage * Phase II enrollment * Gleason \>= 9, PSA =\< 150 ng/mL, any T-stage * Gleason 8, PSA \< 20 ng/mL, and \>= T2 * Gleason 8, PSA \>= 20-150 ng/mL, any T-stage * Gleason 7, PSA \>= 20-150 ng/mL, any T-stage * No distant metastases as evaluated by: * Bone scan 90 days prior to registration * Lymph node assessment by computed tomography (CT) or magnetic resonance (MR) of pelvis or nodal sampling within 90 days prior to registration (Please note: Lymph nodes will be considered negative \[N0\] if they are \< 1.5 cm short axis) * History/physical examination within 90 days prior to registration * Age \>= 18 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 180 days prior to registration * Pretreatment serum PSA, obtained prior to any androgen suppression therapy and within 180 days of registration * Phase I patients: Prior androgen suppression for prostate cancer is not allowed prior to registration * Phase II patients: Prior androgen suppression for prostate cancer is allowed =\< 45 days prior to registration * Hemoglobin \>= 9.0 g/dL (within 90 days prior to registration) * Platelets \>= 100,000 cells/mm\^3 (within 90 days prior to registration) * Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (within 90 days prior to registration) * Serum creatinine =\<1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance \>= 30 mL/min estimated using Cockcroft-Gault equation (within 90 days prior to registration) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN (within 90 days prior to registration) * Serum albumin \>= 3 g/dL (within 90 days prior to registration) * Serum potassium \>= 3.5 mmol/L (within 90 days prior to registration) * Serum total bilirubin =\< 1.5 x ULN or direct bilirubin =\< 1 x ULN (Note: in subjects with Gilberts syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is =\< 1.5 x ULN, subject may be eligible) (within 90 days prior to registration) * Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion criteria
* PSA \> 150 ng/mL * Definitive clinical or radiologic evidence of metastatic disease * Pathologically positive lymph nodes or nodes \> 1.5 cm short axis on CT or MR imaging * Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason * Any active malignancy within 2 years of study registration that may alter the course of prostate cancer treatment * Prior systemic therapy for prostate cancer; note that prior therapy for a different cancer is allowable * Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields * Current treatment with first generation anti-androgens (bicalutamide, nilutamide, flutamide). For patients enrolled to phase II, if prior anti-androgens were administered, a washout period of \>= 30 days is required prior to enrollment * Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Uncontrolled acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition * Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>=160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment * Prior allergic reaction to the drugs involved in this protocol (including known allergies, hypersensitivity or intolerance to the excipients of niraparib) * Human immunodeficiency virus (HIV) positive with CD4 count \< 200 cells/microliter * Note that patients who are HIV positive are eligible, provided they have a CD4 count \>= 200 cells/microliter within 90 days prior to registration. Patients receiving treatment with highly active antiretroviral therapy (HAART) will not be eligible due to concern for radiosensitization * Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be affected by these drugs * Any history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) * Prior or current treatment with PARP inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Disease-free Until Completion of Treatment (2 Years From Start of ADT) | Baseline to completion of treatment (two years from start of ADT) | Participants will be considered disease-free if their PSA values remain below 0.1 ng/ml until the completion of treatment. The proportion of patients disease-free at 24 months were to be compared in the two treatment arms using a non-continuity-corrected chi-square test. PSA levels will be assessed prior to the start of RT, at the end of RT, and every three months for 24 months. all PSA values obtained up to and including the two-year landmark must be \< 0.1 ng/ml. Patients who die prior to two years from prostate cancer will be counted as failures. Patients who die from causes other than prostate cancer will be considered non-evaluable for the primary endpoint. Patients still under follow-up but who have a missing PSA value at two years or more than two missing values prior to two years will also be counted as failures. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Alive (Overall Survival) | From baseline to death or last follow-up, analyzed after phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component. | Survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test. |
| Percentage of Participants With Prostate Cancer Deaths (Prostate Cancer-specific Survival) | From baseline to death or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component. | Prostate cancer death rates were to be estimated using the cumulative incidence method, treating deaths due to other causes as competing risks. The treatment arms were to be compared using the Fine-Gray test |
| Percentage of Participants With Pathologic Complete Response (pCR) at Two Years | At two years | Complete response was to be determined by a12-core biopsy. Treatment arms were to be compared using a chi-square test. |
| Percentage of Participants With Local/Regional or Distant Progression | From baseline to local/regional or distant progression, death, or last follow-up, whichever occurs first, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component. | Progression rates were to be estimated using the cumulative incidence method, treating deaths as competing risks. The treatment arms were to be compared using the Fine-Gray test |
| Percentage of Participants With Distant Metastases | From baseline to distant metastasis, death, or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component. | Distant metastases rates were to be estimated using the cumulative incidence method, treating death as a competing risk. The treatment arms were to be compared using the Fine-Gray test |
| Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival) | From baseline to biochemical progression or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component. | Biochemical progression is defined as PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or death from prostate cancer. Biochemical progression-free survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test. |
| Number of Participants by Highest Grade Adverse Event Reported | From baseline to last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component. | Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Adverse events were to be categorized as early (within 90 days of completion of radiotherapy) or late (more than 90 days after the completion of radiotherapy).The number of participants per grade was to be compared between the arms for early, late, and all adverse events using chi-square or Fisher exact tests |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORM. D Michaelson
NRG Oncology
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I, Dose Level 1 (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity.
\*niraparib dose level 1: 100 mg. | 6 |
| Phase I, Dose Level 2 (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment is given in the absence of disease progression or unacceptable toxicity.
\*niraparib dose level 2: 100 mg during IMRT 200 mg otherwise. | 5 |
| Phase I, Dose Level 3 (Niraparib, GnRH, IMRT) Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months and concurrent niraparib PO QD\* for the first 12 months. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy. Treatment given in the absence of disease progression or unacceptable toxicity.
\*niraparib dose level 3: 200 mg. | 6 |
| Total | 17 |
Baseline characteristics
| Characteristic | Phase I, Dose Level 1 (Niraparib, GnRH, IMRT) | Phase I, Dose Level 2 (Niraparib, GnRH, IMRT) | Phase I, Dose Level 3 (Niraparib, GnRH, IMRT) | Total |
|---|---|---|---|---|
| Age, Continuous | 72.5 years | 74 years | 71 years | 72 years |
| Baseline Prostate-specific antigen (PSA) PSA ≥ 20-150 ng/mL | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Baseline Prostate-specific antigen (PSA) PSA < 20 ng/mL | 5 Participants | 5 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gleason score 10 | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Gleason score 9 | 5 Participants | 5 Participants | 6 Participants | 16 Participants |
| N-Stage N0 | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| N-Stage N1 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 6 Participants | 17 Participants |
| T-Stage T1 | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| T-Stage T2 | 6 Participants | 2 Participants | 3 Participants | 11 Participants |
| T-Stage T3 | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| T-Stage T4 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 5 / 5 | 6 / 6 |
| serious Total, serious adverse events | 3 / 6 | 3 / 5 | 3 / 6 |
Outcome results
Primary
Number of Participants Disease-free Until Completion of Treatment (2 Years From Start of ADT)
Participants will be considered disease-free if their PSA values remain below 0.1 ng/ml until the completion of treatment. The proportion of patients disease-free at 24 months were to be compared in the two treatment arms using a non-continuity-corrected chi-square test. PSA levels will be assessed prior to the start of RT, at the end of RT, and every three months for 24 months. all PSA values obtained up to and including the two-year landmark must be \< 0.1 ng/ml. Patients who die prior to two years from prostate cancer will be counted as failures. Patients who die from causes other than prostate cancer will be considered non-evaluable for the primary endpoint. Patients still under follow-up but who have a missing PSA value at two years or more than two missing values prior to two years will also be counted as failures.
Time frame: Baseline to completion of treatment (two years from start of ADT)
Population: Eligible and evaluable phase II participants followed for two years after start of ADT. The study did/will not advance to the phase II component.
Secondary
Number of Participants by Highest Grade Adverse Event Reported
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Adverse events were to be categorized as early (within 90 days of completion of radiotherapy) or late (more than 90 days after the completion of radiotherapy).The number of participants per grade was to be compared between the arms for early, late, and all adverse events using chi-square or Fisher exact tests
Time frame: From baseline to last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Population: Eligible phase II participants. The study did not and will not advance to the phase II component.
Secondary
Percentage of Participants Alive Without Biochemical Progression (Biochemical Progression-free Survival)
Biochemical progression is defined as PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or death from prostate cancer. Biochemical progression-free survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test.
Time frame: From baseline to biochemical progression or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Population: Eligible phase II participants. The study did/will not advance to the phase II component.
Secondary
Percentage of Participants With Distant Metastases
Distant metastases rates were to be estimated using the cumulative incidence method, treating death as a competing risk. The treatment arms were to be compared using the Fine-Gray test
Time frame: From baseline to distant metastasis, death, or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Population: Eligible phase II participants. The study did not and will not advance to the phase II component.
Secondary
Percentage of Participants With Local/Regional or Distant Progression
Progression rates were to be estimated using the cumulative incidence method, treating deaths as competing risks. The treatment arms were to be compared using the Fine-Gray test
Time frame: From baseline to local/regional or distant progression, death, or last follow-up, whichever occurs first, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Population: Eligible phase II participants. The study did/will not advance to the phase II component.
Secondary
Percentage of Participants With Pathologic Complete Response (pCR) at Two Years
Complete response was to be determined by a12-core biopsy. Treatment arms were to be compared using a chi-square test.
Time frame: At two years
Population: Eligible phase II participants with 12-core biopsy at 24 months. The study did/will not advance to the phase II component.
Secondary
Percentage of Participants With Prostate Cancer Deaths (Prostate Cancer-specific Survival)
Prostate cancer death rates were to be estimated using the cumulative incidence method, treating deaths due to other causes as competing risks. The treatment arms were to be compared using the Fine-Gray test
Time frame: From baseline to death or last follow-up, analyzed after all phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Population: Eligible phase II participants. The study did/will not advance to the phase II component.
Secondary
Percent of Participants Alive (Overall Survival)
Survival rates were to be estimated using the Kaplan-Meier method and the treatment arms were to be compared using a log-rank test.
Time frame: From baseline to death or last follow-up, analyzed after phase II participants have been followed for two years, which was expected to occur 3.5 years from start of phase II component.
Population: Eligible phase II participants. The study did/will not advance to the phase II component.
Other Pre-specified
Maximum Tolerated Dose (MTD) of Niraparib/ Preferred Niraparib Dose for Phase II Component
MTD was determined using the classic 3+3 design to determine the safety of each dose level (DL) from the number of participants with dose limiting toxicities (DLTs), starting with DL1. The highest DL deemed safe was to be considered the MTD. The timing of the 3-patient cohorts took into account the previously established safety of concurrent ADT and 200 mg niraparib and the need to more clearly establish the safety of niraparib concurrent with RT. A DLT is defined as any treatment-related gastrointestinal or genitourinary grade 3 or higher AE lasting \> 1 week, despite maximal medical interventions, and any treatment-related grade 4 AEs lasting \> 1 week. Relationship to treatment was determined by the responsible clinician. Study chairs reviewed possible DLTs for final determination. Niraparib dose level (mg PO QD) definitions \[First 8 weeks with ADT, 6-8 weeks with ADT and RT, remaining time of the 12 months\]: * DL1: 100, 100, 100 * DL2: 200, 100, 200 * DL3: 200, 200, 200
Time frame: From start of combined ADT and niraparib to six months
Population: Eligible and evaluable phase I participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II, Arm I (GnRH, IMRT) | Maximum Tolerated Dose (MTD) of Niraparib/ Preferred Niraparib Dose for Phase II Component | 3 Dose level |
Other Pre-specified
Number of Participants Who Experienced Dose-limiting Toxicities (DLT)
A DLT is defined as any treatment-related gastrointestinal or genitourinary grade 3 or higher AE lasting \> 1 week, despite maximal medical interventions, and any treatment-related grade 4 AEs lasting \> 1 week. Relationship to treatment was determined by the responsible clinician. Study chairs reviewed possible DLTs for final determination.
Time frame: From start of combined ADT and niraparib to six months
Population: Eligible and evaluable phase I participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase II, Arm I (GnRH, IMRT) | Number of Participants Who Experienced Dose-limiting Toxicities (DLT) | 0 Participants |
| Phase II, Arm II (Niraparib, GnRH, IMRT) | Number of Participants Who Experienced Dose-limiting Toxicities (DLT) | 0 Participants |
| Phase I, Dose Level 3 (Niraparib, GnRH, IMRT) | Number of Participants Who Experienced Dose-limiting Toxicities (DLT) | 0 Participants |
Other Pre-specified
Percentage of Participants With Gene Alterations Detected by Targeted Exome Sequencing
The percentage of patients with baseline or post-therapy alterations in targeted genes would be reported and the association between the occurrence of alterations and clinical outcomes would be assessed.
Time frame: From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene mutation data produced
Population: Eligible phase II participants with gene alteration data. The study did not and will not advance to the phase II component.
Other Pre-specified
Percentage of Participants With Gene Expression Determined by High-density Affymetrix Oligonucleotide Array to Profile the Transcriptome of Tumor Samples
The percentage of participants with baseline or post-therapy gene expression and the association between the occurrence of alterations and clinical outcomes would be assessed.
Time frame: From baseline to death or last follow-up, analyzed after all participants have been followed for two years and gene expression data generated.
Population: Eligible phase II participants with gene expression data. The study did not and will not advance to the phase II component.
Other Pre-specified
Percentage of Participants With Single Nucleotide Polymorphisms From Whole Blood Samples
The percentage of patients with baseline or post-therapy polymorphism would be reported and the association between the occurrence of alterations and clinical outcomes would be assessed.
Time frame: From baseline to death or last follow-up, analyzed after all participants have been followed for two years and polymorphism data generated.
Population: Eligible phase II participants with polymorphism data. The study did not and will not advance to the phase II component.