Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02788201|
Recruitment Status : Recruiting
First Posted : June 2, 2016
Last Update Posted : May 20, 2019
Advanced urothelial cancer has no cure. But only a few chemotherapy drugs have been tested for it. The Co-eXpression ExtrapolatioN (COXEN) model predicts if cells respond to treatment. It may also help determine which drugs fight urothelial cancer based on the characteristics of a tumor. Researchers want to test if this model can choose the best therapy for advanced urothelial cancer within 3 weeks and how tumors respond to the next best therapy.
To test if the COXEN model can choose the best therapy for advanced urothelial cancer within 3 weeks.
People ages 18 and older whose urothelial cancer has spread after at least 1 line of chemotherapy
Participants will be screened with medical history, physical exam, blood and urine tests, and tumor scans.
Participants will provide a tumor sample from a previous surgery and a new biopsy. A needle will remove a small piece of tumor.
Participants will repeat screening tests, plus have an EKG and scan. For the scan, they will get an injection of radioactive drug. They will lie in a machine that takes pictures.
Participants will take the drugs assigned by the COXEN model. They will have visits every 2 3 weeks. These will include blood and urine tests.
Participants will have tumor scans every 8 9 weeks.
Participants may have another biopsy.
Participants will take the drugs until they can t tolerate the side effects or their cancer worsens. They may be assigned to a second COXEN therapy.
Participants will have a follow-up visit 4 5 weeks after their last drug dose.
Participants will be contacted by phone every few months until death.
|Condition or disease||Intervention/treatment||Phase|
|Urothelial Carcinoma Bladder Cancer Urinary Bladder Neoplasms||Drug: 75 approved agents Other: COXEN||Phase 2|
Hide Detailed Description
- Patients presenting de novo with metastatic bladder cancer, or developing visceral metastatic disease after local treatment, are incurable with currently available therapeutic modalities.
- Only a small number of chemotherapeutic agents have been tested and very few have some single agent activity in the treatment of metastatic urothelial carcinoma. However most (>100) FDA approved anticancer agents have yet to be tested in this disease.
- Novel approaches to the development of genomic predictors of chemosensitivity that do not require clinical trials for their identification are urgently needed in order to identify agents that are clinically effective when either repurposed or discovered de novo specifically for urothelial carcinoma. Such repurposing of an FDA approved anticancer agent in order to advance therapy from one cancer to another would require only minimal clinical development, saving billions of dollars and reducing the time required to reach routine clinical practice.
- Our established extramural-intramural NCI collaboration pulls together significant expertise in biomarker development and clinical trial design in bladder cancer. The innovation of this group lies not only in the novel scientific approaches i.e. CoeXpression ExtrapolatioN (COXEN) under investigation, but also in the successful creation of a cohesive multi-institutional research collaboration dedicated to improved clinical outcomes in bladder cancer patients.
- COXEN uses molecular profiles as a Rosetta Stone for translating drug sensitivities of one set of cancers into predictions for another completely independent set of cell lines or human tumors. The COXEN methodology has been scrutinized and deemed methodologically sound by peer review. The ability of COXEN to predict drug effectiveness in patients a priori, from purely in vitro assays, is unique as no other tool currently either in practice or in development provides similar results.
- To determine the feasibility of using the Co-eXpression ExtrapolatioN (COXEN) model in making a real-time treatment decision (within 3 weeks) in patients with advanced urothelial carcinoma.
- Patients must have a histologically confirmed diagnosis of metastatic, progressive urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis.
- Patients must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging.
Patients must have at least:
- One measurable site of disease (according to RECIST criteria)
- Or, appearance of one new bone lesion
- Patients must have been previously treated, as defined by treatment with at least one prior cytotoxic chemotherapy regimen or agent. Patients may have received any number of prior cytotoxic agents.
- Archival tumor tissue must be available for enrollment.
- Tumor amenable to biopsy will be mandatory for this study.
- 18 years of age or older
- ECOG performance status <2 (Karnofsky >60%)
- This will be a pilot single-arm, open-label study using the COXEN score to select the best next therapy from a list of 75 FDA approved anti-neoplastic drugs, in patients with metastatic bladder cancer who have progressed despite treatment with cytotoxic chemotherapy. Combinations of the listed agents may also be utilized provided that phase 1 data are available.
- The COXEN algorithm requires a multi-step process (pathology, tissue processing, mRNA profiling, bioinformatics, etc.) and is potentially labor intensive and time intensive.
- Given the disease state of patients eligible for this protocol, using this algorithm to select a treatment would only be a worthwhile process to undertake if it can be demonstrated that a very high fraction of patients are likely to obtain the benefit from the procedure.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Clinical Trial of Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma|
|Actual Study Start Date :||March 27, 2017|
|Estimated Primary Completion Date :||July 1, 2020|
|Estimated Study Completion Date :||July 1, 2021|
Experimental: Arm 1
Treatment regimen selected by COXEN model
Drug: 75 approved agents
One or combination of agents: Abiraterone, Arsenic Trioxide, Asparaginase Escherichia coli source, Axitinib, Azacitidine, Bendamustine, Bleomycin, Bortezomib, Busulfan, Carboplatin, Carfilzomib, Carmustine, Chlorambucil, Cisplatin, Cladribine, Clofarabine, Crizotinib, Cytarabine, Dacarbazine, Dactinomycin, Dasatinib, Daunorubicin, Decitabine, Docetaxel, Doxorubicin, Epirubicin, Eribulin, Erlotinib, Estramustine, Etoposide, Exemestane, Floxuridine, Fludarabine, Fluorouracil, Gefitinib, Gemcitabine, Hydroxyurea, Idarubicin, Ifosfamide, Imatinib, Irinotecan, Ixabepilone, Lapatinib, Lomustine, Mechlor, Melphalan, Mercapto, Methotrexate, Mitomycin, Mitotane, Mitoxantrone, Nilotinib, Oxaliplatin, Paclitaxel, Pazopanib, Pentostatin, Romidepsin, Ruxolitinib, Sorafenib, Streptozocinm, Sunitinib, Tamoxifen, Temsirolimus, Teniposide, Thioguanine, Thiotepa, Topotecan, Toremifene, Tretinoin, Vandetanib, Vemurafenib, Vinblastine, Vincristine, Vismodegib, and/or Vorinostat
The COXEN algorithm will be used to determine the next best therapy from among 75 FDA approved agents (single agent or combination) in patients that have progressed on at least one chemotherapy regimen.
- Percentage of patients success assigned a treatment within 3 weeks [ Time Frame: time to treatment assignment (~3-5 weeks) ]Treatment combination assigned by the COXEN algorithm.
- Time to disease progression [ Time Frame: Progression ]Radiological assessment every 2 cycles to measure change intumor size until tumors increase.
- Objective Response Rate [ Time Frame: end of treatment ]Proportion of patients whose tumors shrunk after therapy.
- average time that patients survive after COXEN intervention [ Time Frame: Death ]Median amount of time subject survives without disease progression after treatment.
- Summary of Adverse events [ Time Frame: 30 days after the last dose ]List of adverse event frequency
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02788201
|Contact: Marissa B Mallek, R.N.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Andrea B Apolo, M.D.||National Cancer Institute (NCI)|