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S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer (COXEN)

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ClinicalTrials.gov Identifier: NCT02177695
Recruitment Status : Recruiting
First Posted : June 30, 2014
Last Update Posted : July 13, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group

June 11, 2014
June 30, 2014
July 13, 2017
July 2014
February 2020   (Final data collection date for primary outcome measure)
The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores. [ Time Frame: Up to 5 years ]

This will be done in two ways:

  • By assessing whether the treatment-specific COXEN score is prognostic of pT0 rate or ≤ pT1 in this patient population and to assess in a preliminary fashion whether the COXEN score is a predictive factor distinguishing between these two chemotherapy regimens. .
  • By evaluating the correlation between the GC- and the DDMVAC-COXEN score.
Same as current
Complete list of historical versions of study NCT02177695 on ClinicalTrials.gov Archive Site
  • Predictability of the CO-eXpression ExtrapolatioN (COXEN) score to direct which of the two regimens the patient should receive: gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC) [ Time Frame: Up to 5 years ]
    Each of the two treatment-specific COXEN scores will be evaluated in separate logistic regression analyses containing indicators for age group, gender, clinical T-stage, grade and treatment arm.
  • Overall survival [ Time Frame: Up to 5 years ]
  • Pathologic T0 rate evaluation: gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC) [ Time Frame: Up to 5 years ]
  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Up to 6 months ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Same as current
Not Provided
Not Provided
 
S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer
A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer
The primary focus of this study is to see if looking at tumor biomarkers using a program called coexpression extrapolation or "COXEN" may predict a patient's response to chemotherapy before surgery.
The COXEN program will not select a patient's therapy, but the type of chemotherapy that he/she will receive will be randomly decided. The patient's response to chemotherapy will be used to test the usefulness of the COXEN program, which is the main goal of this trial. Other potential tests to predict a patient's response to chemotherapy will also be evaluated. In this study, the patient may receive the treatment in Arm 1 (gemcitabine and cisplatin) or the treatment in Arm 2 [methotrexate, vinblastine, doxorubicin, cisplatin, and filgrastim (or pegfilgrastim)]. There will be about 184 people taking part in this study (92 in each arm).
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Bladder Cancer
  • Drug: Gemcitabine
    Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
    Other Name: Gemzar
  • Drug: Cisplatin

    Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle).

    Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.

    Other Name: Platinol
  • Drug: Methotrexate
    Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
    Other Name: Trexall
  • Drug: Vinblastine
    Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
    Other Name: Velban
  • Drug: Doxorubicin
    Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
    Other Name: Adriamycin
  • Drug: Filgrastim
    Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
    Other Name: Neupogen
  • Experimental: Gemcitabine & Cisplatin
    Gemcitabine, 1000 mg/m2, IV, Days 1&8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles
    Interventions:
    • Drug: Gemcitabine
    • Drug: Cisplatin
  • Experimental: Dose Dense MVAC
    Methotrexate, 30 mg/m2, IV, Day 1, q 14 days x 4 cycles Vinblastine, 3 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Doxorubicin, 30 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1 or 2, q 14 days x 4 cycles Filgrastim, 5 mcg/kg, SubQ/IV, Days 3-7, q 14 days x 4 cycles
    Interventions:
    • Drug: Cisplatin
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin
    • Drug: Filgrastim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
184
Same as current
October 2022
February 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically proven bladder cancer (pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma histologies are excluded).
  • Stage cT2-T4a N0 M0 disease.
  • Documented muscle invasive disease with at least one of the following: disease measuring at least 10 mm on cross-sectional imaging OR the presence of tumor-associated hydronephrosis.
  • Staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest within 56 days prior to registration. If alkaline phosphatase is above the treating institution's upper limit of normal (ULN), presence of suspicious bone pain, or if other clinical suspicion, a whole body bone scan is required within 56 days prior to registration.
  • Performance status = 0 or 1
  • 18 years of age or older
  • Must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission that is sufficient for COXEN testing and must agree to submission of 20 (10 micron) slides plus 2 (5 micron) slides from the start and end of the 20 slides for a total of 22 unstained slides.
  • Must agree to collection of tissue (if residual disease is present), urine, and whole blood.
  • Must agree to participate in the translational medicine studies outlined in the protocol

Exclusion Criteria:

  • Prior systemic cytotoxic chemotherapy or systemic anthracycline
  • Peripheral neuropathy >/= Grade 2
  • Class III/IV heart failure or known left ventricular ejection fraction (LVEF) < 50%
  • Clinically relevant hearing impairment > Grade 2
  • Renal function, calculated creatinine clearance < 60 mL/min
  • Hepatic function, total bilirubin > 1.5 x institutional upper limit of normal (IULN) (or > 2.5 x IULN with Gilbert's disease); AST & ALT > 2 X IULN
  • Hematologic function, absolute neutrophil count (ANC) < 1,500/mcL, hemoglobin < 9 g/dL, and platelets < 100,000/mcL
  • Hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or filgrastim/pegfilgrastim
  • Incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.)
  • Pregnant or nursing females
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. However, patients with localized prostate cancer who are being followed by an active surveillance program are eligible.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: Nicki Trevino 210-614-8808 ext 1007 ntrevino@swog.org
Contact: Dana Sparks, M.A.T. 210-614-8808 ext 1004 dsparks@swog.org
United States
 
 
NCT02177695
S1314
S1314 ( Other Identifier: SWOG )
NCI-2014-00850 ( Other Identifier: National Cancer Institute )
U10CA180888 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Southwest Oncology Group
Southwest Oncology Group
National Cancer Institute (NCI)
Study Chair: Thomas W. Flaig, M.D. University of Colorado, Denver
Southwest Oncology Group
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP