Metastatic Urothelial CarcinomaPhase 2NCT02693717
Pemetrexed Disodium in Treating Patients With Previously Treated Metastatic Urothelial Cancer
A Phase 2 study testing Laboratory Biomarker Analysis and Pemetrexed Disodium in people with Metastatic Urothelial Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Urothelial Carcinoma
- What is being tested?
- Laboratory Biomarker Analysis and Pemetrexed Disodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 9 May 2017to 30 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 15Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the 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:
- 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.
- Conditions
- Metastatic Urothelial Carcinoma
- Being tested
- Laboratory Biomarker Analysis, Pemetrexed Disodium
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Pemetrexed DisodiumDrug
Also called Alimta, LY231514, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidine-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pemetrexed disodium) | Experimental | Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Pemetrexed Disodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 5 years
Secondary outcomes (2)
Progression-free Survival
Progression-free survival will be estimated and plotted with the methods of Kaplan and Meier.
Measured: 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
Overall Survival
Overall survival will be estimated and plotted with the methods of Kaplan and Meier.
Measured: Time from trial entry to death from any cause, assessed at 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2016 (estimated)
- Study start9 May 2017
- Primary completion30 Dec 2019
- Study completion30 Dec 2019
Why it stopped: The trial was closed due to the changing efficacy of treatments for metastatic urothelial cancer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jianjun Gao, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02693717
- Sponsor's protocol ID
- 2015-0592
- Other IDs
- NCI-2016-00390, 2015-0592, P30CA016672
- Status last verified
- May 2021
- First submitted
- 18 Feb 2016
- Last updated
- 20 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Alhalabi O, Chen J, Zhang Y, Lu Y, Wang Q, Ramachandran S, Tidwell RS, Han G, Yan X, Meng J, Wang R, Hoang AG, Wang WL, Song J, Lopez L, Andreev-Drakhlin A, Siefker-Radtke A, Zhang X, Benedict WF, Shah AY, Wang J, Msaouel P, Zhang M, Guo CC, Czerniak B, Behrens C, Soto L, Papadimitrakopoulou V, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee J, Roth J, Swisher S, Wistuba I, Heymach J, Wang J, Campbell MT, Efstathiou E, Titus M, Logothetis CJ, Ho TH, Zhang J, Wang L, Gao J. MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers. Nat Commun. 2022 Apr 4;13(1):1797. doi: 10.1038/s41467-022-29397-z.
PubMed 35379845
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02693717
- Acronym / sponsor ID
- 2015-0592
- Conditions
- Metastatic Urothelial Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was closed due to the changing efficacy of treatments for metastatic urothelial cancer.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 9 May 2017 (actual)
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 29 Feb 2016 (estimated)
- Results
- Posted 20 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (pemetrexed disodium) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Pemetrexed DisodiumPatients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pemetrexed disodium) |
| Pemetrexed DisodiumAlso: Alimta, LY231514, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidine-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium SaltGiven IV | Drug | Treatment (pemetrexed disodium) |
Primary outcome
Objective Response Rates
Time frame: 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.
2 secondary outcomes
Progression-free Survival
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
Overall Survival
Time frame: Time from trial entry to death from any cause, assessed at 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35379845Alhalabi O, Chen J, Zhang Y, Lu Y, Wang Q, Ramachandran S, Tidwell RS, Han G, Yan X, Meng J, Wang R, Hoang AG, Wang WL, Song J, Lopez L, Andreev-Drakhlin A, Siefker-Radtke A, Zhang X, Benedict WF, Shah AY, Wang J, Msaouel P, Zhang M, Guo CC, Czerniak B, Behrens C, Soto L, Papadimitrakopoulou V, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee J, Roth J, Swisher S, Wistuba I, Heymach J, Wang J, Campbell MT, Efstathiou E, Titus M, Logothetis CJ, Ho TH, Zhang J, Wang L, Gao J. MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers. Nat Commun. 2022 Apr 4;13(1):1797. doi: 10.1038/s41467-022-29397-z.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
Related trials for Metastatic Urothelial Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 3
A Study Comparing the Combination of Pembrolizumab and Sacituzumab Govitecan-hziy Versus Standard of Care in the Treatment of Advanced Urothelial Cancer
Locally Advanced Urothelial Carcinoma, Metastatic Urothelial Carcinoma
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jianjun Gao principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis and Pemetrexed Disodium in people with Metastatic Urothelial Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rates (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02693717, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2021.