Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer
Conditions
Brief summary
This phase II trial studies how well giving oxaliplatin and pemetrexed disodium together works in treating patients with refractory hormone-resistant prostate cancer. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving oxaliplatin together with pemetrexed disodium may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To determine the response rate by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, prostate-specific antigen (PSA) response by the PSA Working Group criteria, and overall clinical benefit defined by summation of RECIST complete responses (CR) plus RECIST partial responses (PR) plus PSA PRs. SECONDARY OBJECTIVES: I. To determine time to progression in patients with hormone-refractory prostate cancer (HRPC) receiving oxaliplatin and pemetrexed. II. To describe the safety profile of this treatment. III. Pain response will be evaluated in an exploratory manner. IV. Undertake a pilot analysis of excision repair cross-complementing 1 (ERCC1) expression levels and polymorphisms, looking at their ability to predict response to platinum therapy. OUTLINE: Patients receive oxaliplatin intravenously (IV) over 2 hours and pemetrexed disodium IV on day 1. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.
Interventions
DRUGoxaliplatin
Given IV
DRUGpemetrexed disodium
Given IV
OTHERquestionnaire administration
Ancillary studies
OTHERlaboratory biomarker analysis
Correlative studies
GENETICreverse transcriptase-polymerase chain reaction
Correlative studies
GENETICpolymorphism analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
University of Southern California
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed prostate cancer * Measurable disease on computed tomography (CT) or evaluable disease on bone scan with an elevated PSA * For patients who did not initially present with metastatic disease, definitive treatment with either radical prostatectomy or external beam radiation is permitted * Documented progression on (a) two prior hormone treatments AND (b) one or two chemotherapy regimens * Documented progression on two prior hormone therapies is defined as orchiectomy followed by anti-adrenal medication upon progression OR gonadotropin-releasing hormone (GnRH) analog +/- androgen receptor blocker with addition or subtraction upon progression; castrate level of testosterone must be documented at study entry * Documented progression on taxane-based chemotherapy; in addition, patients may have failed a second prior chemotherapy regimen * Palliative radiation therapy for metastatic disease is allowed only if less than 25% of total body bone marrow was irradiated; 28 days must have elapsed since completion of radiation therapy (RT) with bone marrow recovery; soft tissue disease irradiated in the prior 2 months may not be designated as measurable disease * ECOG performance score of 0-2 * Absolute neutrophil count (ANC) \>= 1500/uL * Platelet count \>= 100,000/uL * Creatinine clearance \>= 45 mL/min * Serum total bilirubin =\<1.5 mg/dL * Alkaline phosphatase =\< 3x the upper limit of normal (ULN) for the reference lab (=\< 5x the ULN for patients with known hepatic metastases) and no upper limit for patients with known bone metastases * Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) =\< 3x the ULN for the reference lab (=\< 5x the ULN for patients with known hepatic metastases) * Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy * Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial * Men of childbearing potential must consent to use barrier contraception while on treatment and for 90 days thereafter * Patients with pleural or peritoneal effusions are eligible * Willingness and ability to take vitamin supplementation and steroid premedication as specified in protocol * Patients with superficial bladder cancer or skin cancer who have second malignancy within 5 years which was removed with curative intent
Exclusion criteria
* Active infection or with a fever \>= 38.5 degrees Celsius (C) within 3 days of the first scheduled protocol treatment * Patients with brain metastases * Prior malignancy within the past 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or superficial bladder cancer * Known hypersensitivity to any of the components of oxaliplatin or pemetrexed * Received radiotherapy to more than 25% of their bone marrow, or patients who received any radiotherapy within 4 weeks of entry * Received treatment with strontium * Receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment * Life expectancy \< 6 months * Peripheral neuropathy \>= Grade 2 * Any other medical condition, including mental illness or substance abuse * History of allogeneic transplant * Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated, or both) * Inability to stop nonsteroidal anti-inflammatory drugs (NSAIDS) for a period of 2 days before, the day of, and 2 days following administration of Alimta; 5 days before, the day of, and 2 days following administration of Alimta for long-acting NSAIDS
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | RECIST evaluation: Baseline, after every 2 courses, and then every 6 months after off-study, up to 1 year. PSA evaluation: baseline, day 1 of each course, final evaluation, and then every 6 months after off-study, up to 1 year | For patients with measurable disease, the RECIST 1.0 criteria was used to determine response. Complete Response = disappearance of all target lesions, Partial Response = greater or equal to 30% decrease in sum of longest diameter or target lesions, Stable Disease = \<30% decrease or \<20% increase, Progressive Disease = greater or equal to 20% increase in longest diameter of target lesions. For patients who do not have measurable disease by RECIST, the response was based on PSA response defined by Prostate Cancer Working Group criteria (1999) as 50% reduction in PSA confirmed on a second measurement at least 4 weeks later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disease Progression and Overall Survival | Baseline, after every 2 courses, and then every 6 months after off-study (RECIST) until progression; or baseline, day 1 of each course, at the final evaluation, and then every 6 months after off-study (PSA) until progression | Progression-free survival was defined as the time from the first infusion of study treatment to the date of radiographic disease progression according to RECIST 1.0, or until two consecutive PSA rises occurred with an absolute increase of 5 ng/mL and a 50% relative increase over baseline. For patients without documented disease progression, the date of death or last follow-up without disease progression was used. |
| Number of Participants With Serious Adverse Events (SAEs) | Baseline, days 1 and 7 of each course, and at last evaluation, up to 1 year | Safety evaluation according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
Countries
United States
Participant flow
Recruitment details
The study was activated on June 14, 2006 and was closed to accrual on May 11, 2009 after accruing 47 subjects. Participants were recruited at LAC+USC Medical Center and the USC/Norris Cancer Hospital.
Pre-assignment details
The study had no pre-assignment criteria.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy and Enzyme Inhibitor) Patients receive oxaliplatin IV over 2 hours and pemetrexed disodium IV on day 1. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy and Enzyme Inhibitor) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 31 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 9 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 47 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 47 |
| serious Total, serious adverse events | 35 / 47 |
Outcome results
Primary
Best Overall Response
For patients with measurable disease, the RECIST 1.0 criteria was used to determine response. Complete Response = disappearance of all target lesions, Partial Response = greater or equal to 30% decrease in sum of longest diameter or target lesions, Stable Disease = \<30% decrease or \<20% increase, Progressive Disease = greater or equal to 20% increase in longest diameter of target lesions. For patients who do not have measurable disease by RECIST, the response was based on PSA response defined by Prostate Cancer Working Group criteria (1999) as 50% reduction in PSA confirmed on a second measurement at least 4 weeks later.
Time frame: RECIST evaluation: Baseline, after every 2 courses, and then every 6 months after off-study, up to 1 year. PSA evaluation: baseline, day 1 of each course, final evaluation, and then every 6 months after off-study, up to 1 year
Population: All participants who received at least 1 cycle of treatment were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Chemotherapy and Enzyme Inhibitor) | Best Overall Response | Complete Response | 0 Participants |
| Treatment (Chemotherapy and Enzyme Inhibitor) | Best Overall Response | Partial Response | 14 Participants |
| Treatment (Chemotherapy and Enzyme Inhibitor) | Best Overall Response | Stable Disease | 21 Participants |
| Treatment (Chemotherapy and Enzyme Inhibitor) | Best Overall Response | Progressive Disease | 8 Participants |
| Treatment (Chemotherapy and Enzyme Inhibitor) | Best Overall Response | Inevaluable | 4 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
Safety evaluation according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time frame: Baseline, days 1 and 7 of each course, and at last evaluation, up to 1 year
Population: All participants who started treatment were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy and Enzyme Inhibitor) | Number of Participants With Serious Adverse Events (SAEs) | 35 Participants |
Secondary
Time to Disease Progression and Overall Survival
Progression-free survival was defined as the time from the first infusion of study treatment to the date of radiographic disease progression according to RECIST 1.0, or until two consecutive PSA rises occurred with an absolute increase of 5 ng/mL and a 50% relative increase over baseline. For patients without documented disease progression, the date of death or last follow-up without disease progression was used.
Time frame: Baseline, after every 2 courses, and then every 6 months after off-study (RECIST) until progression; or baseline, day 1 of each course, at the final evaluation, and then every 6 months after off-study (PSA) until progression
Population: Participants who received at least the first infusion of treatment were included.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment (Chemotherapy and Enzyme Inhibitor) | Time to Disease Progression and Overall Survival | Median Survival | 12.0 Months |
| Treatment (Chemotherapy and Enzyme Inhibitor) | Time to Disease Progression and Overall Survival | Median Time to Progression | 5.8 Months |
| Treatment (Chemotherapy and Enzyme Inhibitor) | Time to Disease Progression and Overall Survival | Median Progression Free Survival | 5.4 Months |