Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma

NCT02788201 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16012116-C-0121
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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 electrocardiogram (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.

Conditions

Urothelial Carcinoma; Bladder Cancer; Urinary Bladder Neoplasms

Keywords

COXEN; Bladder Cancer; Molecular Profiles

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Enrolled and Underwent a Biopsy Who Went on to Receive Treatment Within 21 Days

  Participants were assigned a treatment combination by the co-expression extrapolation (COXEN) algorithm. The COXEN algorithm used a multi-step process that involved pathology, tissue processing, messenger ribonucleic acid (mRNA) profiling and bioinformatics, etc. to select a treatment regimen.

  time to treatment assignment, approximately 3 weeks

Secondary Outcomes (5)

• Progression Free Survival

  Every 2 cycles until progression, approximately 4 months.

• Proportion of Patients With an Objective Response

  End of treatment, approximately 4 months.

• Overall Survival

  From date of treatment content until the date of death from any cause or date off study, whichever came first, assessed up to 10 months and 16 days.

• Number of Participants Who Had Adverse Events ≥ Grade 1

  Date treatment consent signed to date off study, approx. 5 mos/ 6 dys for the 1st Grp; 10 mos/16 dys for the 2nd Grp; 8 mos/13 dys for the 3rd Grp; 5 mos/16 dys for the 4th Grp; and 27 dys for the 5th Grp.

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approx. 5 mos/ 6 dys for the 1st Grp; 10 mos/16 dys for the 2nd Grp; 8 mos/13 dys for the 3rd Grp; 5 mos/16 dys for the 4th Grp; and 27 dys for the 5th Grp.

Study Arms (1)

Treatment Regimen

EXPERIMENTAL

Treatment regimen selected by CO eXpression ExtrapolatioN (COXEN) model

Drug: 75 approved agents; Other: COXEN

Interventions

75 approved agents DRUG

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, Streptozocin, Sunitinib, Tamoxifen, Temsirolimus, Teniposide, Thioguanine, Thiotepa, Topotecan, Toremifene, Tretinoin, Vandetanib, Vemurafenib, Vinblastine, Vincristine, Vismodegib, and/or Vorinostat

Treatment Regimen

COXEN OTHER

The CO eXpression ExtrapolatioN (COXEN) algorithm will be used to determine the next best therapy from among 75 Food and Drug Administration (FDA) approved agents (single agent or combination) in patients that have progressed on at least one chemotherapy regimen.

Treatment Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Response Evaluation Criteria in Solid Tumors (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 computed tomography (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. Eastern Cooperative Oncology Group (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

You may not qualify if:

• 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 enrollment.
• 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 Common Terminology Criteria for Adverse Events (CTCAE) less than or equal to Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Andrea Apolo
• Organization: National Cancer Institute

apoloab@nih.gov

301-480-0536

Study Officials

• Andrea B Apolo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 28, 2016
• First Posted: June 2, 2016
• Study Start: March 27, 2017
• Primary Completion: October 23, 2019
• Study Completion: October 23, 2019
• Last Updated: November 6, 2020
• Results First Posted: November 6, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)