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Trial record 1 of 1 for:    s1314
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S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer (COXEN)

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Southwest Oncology Group
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT02177695
First received: June 11, 2014
Last updated: April 20, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Bladder Cancer Drug: Gemcitabine Drug: Cisplatin Drug: Methotrexate Drug: Vinblastine Drug: Doxorubicin Drug: Filgrastim Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) With Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 184
Study Start Date: July 2014
Estimated Study Completion Date: October 2022
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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

Detailed Description:
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).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02177695

Contacts
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

  Show 561 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Thomas W. Flaig, M.D. University of Colorado, Denver
  More Information

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT02177695     History of Changes
Other Study ID Numbers: S1314
S1314 ( Other Identifier: SWOG )
NCI-2014-00850 ( Other Identifier: National Cancer Institute )
U10CA180888 ( US NIH Grant/Contract Award Number )
Study First Received: June 11, 2014
Last Updated: April 20, 2017

Keywords provided by Southwest Oncology Group:
Bladder Cancer
Neoadjuvant Chemotherapy
Coexpression Extrapolation
COXEN
S1314
SWOG

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Gemcitabine
Liposomal doxorubicin
Cisplatin
Methotrexate
Doxorubicin
Vinblastine
Lenograstim
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Dermatologic Agents
Folic Acid Antagonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on June 28, 2017