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BRIEF TITLE: A Phase II Trial to Evaluate Pemetrexed Clinical Responses in Relation to Tumor MTAP Gene Status in Patients With Previously Treated Metastatic Urothelial Carcinoma

A Phase II Trial to Evaluate Pemetrexed Clinical Responses in Relation to Tumor MTAP Gene Status in Patients With Previously Treated Metastatic Urothelial Carcinoma


  • Org Study ID: 2015-0592
  • Secondary ID: NCI-2016-00390
  • NCT ID: NCT02693717
  • NCT Alias:
  • Sponsor: M.D. Anderson Cancer Center - Other
  • Source: M.D. Anderson Cancer Center

Brief Summary

The goal of this clinical research study is to learn if Alimta (pemetrexed) can help to control urothelial cancer (bladder, urethra, and/or ureters) that has spread or cannot be controlled with surgery. The safety of this drug will also be studied. Researchers will also study how a gene called MTAP may affect the way the study drug works. This is an investigational study. Pemetrexed is FDA approved for the treatment of mesothelioma and non small cell lung cancer. Pemetrexed is not FDA approved for urothelial cancer. It is being used for research purposes only. Up to 25 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description


Study Drug Administration:

The day of your first dose of pemetrexed:

- You will start a vitamin pill (folic acid). You will continue to take folic acid every
day by mouth while you are receiving pemetrexed. Folic acid has been found to decrease
some of the side effects of pemetrexed.

- You will start vitamin B12. B12 is given by injection into the muscle. It will be given
every 9 weeks during your treatment. B12 has been found to decrease some of the side
effects of pemetrexed.

- You will start receiving dexamethasone. You will receive dexamethasone by vein over
about 5-15 minutes on Day 1 of each 21-day cycle. You will also take it by mouth twice a
day for 2 days after each dose of pemetrexed to help prevent skin rash.

- If you are able to become pregnant and the study doctor thinks it is needed, the
pregnancy blood test (about 1 tablespoon) will be repeated.

If you are found to be eligible to take part in this study, you will receive pemetrexed by
vein over about 10 minutes on Day 1 of each 21-day cycle.

Study Visits:

On Day 1 of all cycles. If you have had these performed within 7 days, they need not be
repeated.

- You will have a physical exam.

- Blood (about 1-2 tablespoons) will be drawn for routine tests.

Every 3 cycles:

- You will have a bone scan and CT scans and/or MRI to check the status of the disease.

- You will have a PET scan if you had one at screening.

- You will have bone scan if the disease has spread to your bones.

Length of Dosing:

You may take pemetrexed for as long as the doctor thinks it is in your best interest. You may
no longer be able to take the study drug if intolerable side effects occur, or if you are
unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Study Visit:

If the study drug is stopped early, or when you are taken off study for any reason, within 3
weeks of your last dose of study drug the following tests and procedures will be performed:

- You will have a physical exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- If the doctor thinks it is needed, you will have the PET scan, CT scan and/or MRI to
check the status of the disease.

Follow-Up Visits/Calls:

You will have additional follow up visits every 3 months for a total of 5 years. If you are
not able to travel someone will call you to find out how you are doing. The call will last
about 5-10 minutes each time.

Overal Status Start Date Phase Study Type
Recruiting May 9, 2017 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Overall Response Rate (ORR) of Participants with MTAP-deficient vs. MTAP Wild-Type Bladder Cancer Treated With Pemetrexed

Primary Outcome 1 - Time Frame: 63 days

Condition:

  • Bladder Cancer
  • Urothelial Cancer

Eligibility

Criteria:
Inclusion Criteria:

1. 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.

2. 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 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.

3. Patients who have received any non-anti-folate containing neoadjuvant or systemic
chemotherapy are eligible. Any prior intravesical therapy, or immunotherapy is
allowed.

4. Patients must have an ECOG performance status
5. Adequate liver function as defined by AST or ALT documented liver metastases are present.

6. Total bilirubin metastases, who must have a baseline total bilirubin
7. Adequate bone marrow reserves as define by an ANC >/= 1500, and platelets >/= 100,000.

8. Adequate renal function as defined by a normal serum creatinine, or a creatinine
clearance >/= 40 ml/min [either measured using a 24 hour urine, calculated using
Cockcroft-Gault, or estimated using the MDRD method from the National Kidney Disease
Education Program (NKDEP) (the method reported by MDACC laboratories)]

9. 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.

10. inclusion 9 continued: They must also refrain from egg cell donation for 180 days
after the final dose of investigational product; a) 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)

11. inclusion 9 continued: b) 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.

12. The ability to interrupt NSAIDS 2 days before (5 days for long-acting NSAIDs), the day
of, and 2 days following administration of Pemetrexed.

13. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol.

Exclusion Criteria:

1. 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).

2. Patients who received previous anti-folate-containing chemotherapy.

3. 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.

4. Women who are pregnant or breastfeeding.

5. 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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Jianjun Gao, MD, PHD

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Jianjun Gao, MD, PHD

Phone: 713-792-2830

Email: jgao1@mdanderson.org

Link: University of Texas MD Anderson Cancer Center Website

Locations

Facility Status Contact
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting

jgao1@mdanderson.org
MD Anderson Katy Regional Care Center
Houston, Texas 77094
United States
Recruiting Jennifer Wang, MD

MD Anderson Sugarland Regional Care Center
Sugar Land, Texas 77478
United States
Recruiting Jennifer Wang, MD