Metastatic Urothelial Carcinoma
Conditions
Brief summary
This phase II trial studies how well pemetrexed disodium works in treating patients with previously treated urothelial cancer that has spread from the primary site (place where it started) to other places in the body. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES: To determine the objective response rates (ORR) to pemetrexed disodium (pemetrexed) in patients with MTAP-deficient metastatic bladder cancer. SECONDARY OBJECTIVES: I. To determine the progression-free survival (PFS) for patients with MTAP-deficient metastatic bladder cancer treated with pemetrexed. II. To determine the overall survival (OS) for patients with MTAP-deficient metastatic bladder cancer treated with pemetrexed. III. Evaluate the toxicity of pemetrexed therapy for patients with MTAP-deficient metastatic bladder cancer. IV. Collect blood, urine, and tissue for future translational studies. OUTLINE: Patients receive pemetrexed disodium intravenously (IV) over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 weeks and then every 3 months for 5 years.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPemetrexed Disodium
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histological confirmation of metastatic urothelial carcinoma; patients must have sufficient tumor tissues for future MTAP testing and research; histological variants such as glandular, squamous, sarcomatoid, micropapillary, plasmacytoid, and small cell changes will not be allowed for this trial unless these tumors are MTAP-deficient * All patients must have measurable disease and tumors of sufficient sizes for biopsy; in general, liver and lung lesions should be at least 1.0 cm, and patients with lymph node-only disease should have lesions of \>= 1.5 cm in shortest dimension; patients with disease confined to bone may be eligible if a measurable lytic defect is present; the study principal investigator (PI) is the final arbiter in questions related to measurability; patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease * Patients who have received any non-anti-folate containing neoadjuvant or systemic chemotherapy are eligible; any prior intravesical therapy, or immunotherapy is allowed * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x upper limit normal (ULN), or =\< 5 x ULN if documented liver metastases are present * Total bilirubin =\< 1.5 x ULN, except subjects with Gilbert's syndrome or liver metastases, who must have a baseline total bilirubin =\< 3.0 mg/dL * Absolute neutrophil count (ANC) \>= 1500 * Platelets \>= 100,000 * Normal serum creatinine, or a creatinine clearance \>= 40 ml/min (either measured using a 24 hour urine, calculated using Cockroft-Gault, or estimated using the Modification of Diet in Renal Disease \[MDRD\] method from the National Kidney Disease Education Program \[NKDEP\] \[the method reported by M D Anderson Cancer Center (MDACC) laboratories\]) * Females of childbearing potential who are sexually active with a non-sterilized male partner and non-sterilized males must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 180 days after the final dose of investigational product; cessation of contraception after this point should be discussed with a responsible physician * Females of childbearing potential must also refrain from egg cell donation for 180 days after the final dose of investigational product; * Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause) * A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly; the acceptable methods of contraception are: barrier method (e.g. male condom with spermicide, copper T intrauterine device, or levonorgestrel-releasing intrauterine system - Mirena) or hormonal methods (e.g. implants, hormone shot or injection, combined pill, minipill, or patch); non-sterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from days 1-180 post last dose; in addition, they must refrain from sperm donation for 180 days after the final dose of investigational product * The ability to interrupt nonsteroidal antiinflammatory drug (NSAIDS) 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed * The ability to take folic acid, vitamin B12, and dexamethasone according to protocol
Exclusion criteria
* Primary central nervous system (CNS) malignancies or CNS metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable for at least 3 months following prior treatment (radiotherapy or surgery) * Patients who received previous anti-folate-containing chemotherapy * Any other malignancy from which the patient has been disease-free for less than 3 years, except for non-melanoma skin cancer, controlled localized prostate cancer, in situ carcinoma of any site * Women who are pregnant or breastfeeding * Presence of third space fluid which cannot be controlled by drainage; for patients who develop or have baseline clinically significant pleural or peritoneal effusions (on the basis of symptoms or clinical examination) before or during initiation of pemetrexed therapy, consideration should be given to draining the effusion prior to dosing; however, if, in the investigator's opinion, the effusion represents progression of disease, the patient should be discontinued from study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rates | Up to 5 years | Will be defined as the number of subjects with complete response or partial response by Response Assessment in Solid Tumors 1.1 criteria divided by the total number of subjects receiving their first dose of trial therapy. Objective response rates will be summarized using descriptive statistics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time from trial entry to the first documented tumor progression as determined by the investigator using the Response Evaluation Criteria in Solid Tumors 1.1 criteria or death from any cause, assessed at 2 years | Progression-free survival will be estimated and plotted with the methods of Kaplan and Meier. |
| Overall Survival | Time from trial entry to death from any cause, assessed at 2 years | Overall survival will be estimated and plotted with the methods of Kaplan and Meier. |
Countries
United States
Participant flow
Recruitment details
The participants were accrued starting in Sept 2017 through January 2019.
Participants by arm
| Arm | Count |
|---|---|
| Pemetrexed Intravenous infusion 500 mg/m2 every 21 days | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Pemetrexed |
|---|---|
| Age, Continuous | 73.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 4 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Objective Response Rates
Will be defined as the number of subjects with complete response or partial response by Response Assessment in Solid Tumors 1.1 criteria divided by the total number of subjects receiving their first dose of trial therapy. Objective response rates will be summarized using descriptive statistics.
Time frame: Up to 5 years
Population: Study terminated early, no data collected
Secondary
Overall Survival
Overall survival will be estimated and plotted with the methods of Kaplan and Meier.
Time frame: Time from trial entry to death from any cause, assessed at 2 years
Population: Study terminated early, no data collected
Secondary
Progression-free Survival
Progression-free survival will be estimated and plotted with the methods of Kaplan and Meier.
Time frame: Time from trial entry to the first documented tumor progression as determined by the investigator using the Response Evaluation Criteria in Solid Tumors 1.1 criteria or death from any cause, assessed at 2 years
Population: Study terminated early, no data collected