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Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT02788201
Recruitment Status : Recruiting
First Posted : June 2, 2016
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

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.

Objective:

To test if the COXEN model can choose the best therapy for advanced urothelial cancer within 3 weeks.

Eligibility:

People ages 18 and older whose urothelial cancer has spread after at least 1 line of chemotherapy

Design:

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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Pilot Clinical Trial of Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma
Study Start Date : May 28, 2016
Estimated Primary Completion Date : July 1, 2019
Estimated Study Completion Date : July 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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

Other: COXEN
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Time to disease progression [ Time Frame: Progression ]
    Radiological assessment every 2 cycles to measure change intumor size until tumors increase.

  2. Objective Response Rate [ Time Frame: end of treatment ]
    Proportion of patients whose tumors shrunk after therapy.

  3. average time that patients survive after COXEN intervention [ Time Frame: Death ]
    Median amount of time subject survives without disease progression after treatment.

  4. Summary of Adverse events [ Time Frame: 30 days after the last dose ]
    List of adverse event frequency



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • 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), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as more than or equal to 20 mm with conventional techniques or as less than or equal to 10 mm with spiral CT scan.
    • Or, appearance of one new bone lesion
  • Patients must have been previously treated 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.
  • Age more than or equal to 18 years. ECOG performance status less than or equal to 2 (Karnofsky more than or equal to 60%,).
  • Patients must have normal organ and marrow function as defined below:

    • hemoglobin more than or equal to 9 g/dL
    • leukocytes more than or equal to 3,000/mcL
    • absolute neutrophil count more than or equal to 1,200/mcL
    • platelets more than or equal to 75,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
    • creatinine 1.5 x the normal institutional limits

OR

--creatinine clearance more than or equal to 40 mL/min/1.73 m2

  • Because many of the therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • HIV-positive patients on combination antiretroviral therapy may be eligible if there are no pharmacokinetic interactions with the agents used on the study, stable on CART therapy and CD4 is >200 and viral load is undetectable.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • The patient has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks or biologic agents (e.g., cytokines or antibodies) within 4 weeks prior to study enrolllment.
  • Patients who are receiving any investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with brain metastases that are stable after more than or equal to 1 year after primary surgery or radiation will not be excluded.
  • The subject has not recovered to baseline or CTCAE less than or equalto Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients who are Hepatitis B or C positive.
  • Pregnant women are excluded from this study because the agents used in the study have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated with these agents. These potential risks may also apply to other agents used in this study.

Information from the National Library of Medicine

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


Contacts
Contact: Deborah E Allen, R.N. (301) 451-8904 allendeb@mail.nih.gov

Locations
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      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Andrea B Apolo, M.D. National Cancer Institute (NCI)

Additional Information:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02788201     History of Changes
Other Study ID Numbers: 160121
16-C-0121
First Posted: June 2, 2016    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: March 14, 2018

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
COXEN
Bladder Cancer
Molecular Profiles
Algorithm
Biomarkers

Additional relevant MeSH terms:
Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases