Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Gemcitabine

Doxorubicin

Liposomal doxorubicin

Methotrexate

Cisplatin

Lenograstim

Vinblastine

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

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

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

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.

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.

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.

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.

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.

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.

Filgrastim

Thomas W. Flaig, M.D.

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 230 people taking part in this study (115 in each arm).

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 proportion of participants achieving pT0 in both favorable and unfavorable treatment specific-COXEN score categories.

Unit of measure is the number of participants in each category that achieved pT0

_____________________________________________________________________________________________________________________

The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

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.

The proportion of participants achieving \<=pT1 in both favorable and unfavorable treatment specific-COXEN score categories.

Unit of measure is the number of participants in each category that achieved \<= pT1

____________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

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.

To assess in a hypothesis generating fashion, the ability of COXEN to select for an individual chemotherapy regimen (GC vs DDMVAC)

P-values are reported as a measure of whether COXEN can select between GC/DDMVAC and to determine the significance of interactions between treatment specific COXEN scores and treatment arms in models predicting either pT0 or \<= pT1. Interactions with p-values \> 0.05 are interpreted as not significant.

________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

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.

The Pearson and Spearman correlation coefficients for GC-and ddMVAC-COXEN score were calculated and are reported below.

___________________________________________________________________________________________________________________ The relationship of dose-dense methotrexate, vinblastin, doxorubicin, and cisplatin (DDMVAC)- and gemcitabine+cisplatin (GC)- specific CO-eXpression ExtrapolatioN (COXEN) scores

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.

In addition to stratification factors and dichotomous COXEN GEM score, an indicator for treatment arm and the interaction of treatment arm with COXEN GEM score was also included in a logistic regression model. A significant interaction would suggest that the respective COXEN GEM score was able to differentiate whether a patient was more likely to respond to one chemotherapy regimen over another. \*note that this is the same objective at Primary Outcome #3 above - this was erroneously listed twice in the protocol.

Duration from date of randomization to date of death from any cause.

Pathologic complete response rate at the time of cystectomy following GC or DDMVAC treatment

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Grade 3 is less severe than Grade 5.

Grade 3 - Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\* (bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden).

Grade 4 - Life-threatening consequences; urgent intervention indicated. Grade 5 - Death related to AE

\*ADL- Activities of Daily Living

National Cancer Institute (NCI)

SWOG Cancer Research Network

Participants who received protocol treatment and are included in the ITT analysis

Gemcitabine, 1000 mg/m2, IV, Days 1 and 8, q 21 days x 4 cycles Cisplatin, 70 mg/m2, IV, Day 1, q 21 days x 4 cycles

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.

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.

Gemcitabine and Cisplatin

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

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.

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.

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.

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.

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.

Dose Dense MVAC

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

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.

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.

Gemcitabine & Cisplatin

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Clinical T staging based on the TURBT sample and imaging studies

T2- tumor invades muscularis propia T3- tumor invades perivesical tissue T4a- tumor invades prostatic stroma, uterus, vagina

Clinical stage

0- fully active, able to carry out all pre-disease performance without restriction

1- restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature

Zubrod performance status

Coexpression extrapolation (COXEN) score to predict tumor response to treatment with GC.

COXEN algorithm is a novel approach to generate predictive gene expression models for cancer therapy response. COXEN scores(coefficient) for a participant on a therapy were categorized into low/high scores. High scores predict whether a participant has a 'favorable' response-either pT0 (complete disappearance of tumor) or downgrading to \<= pT1 (tumor invades subepithelial connective tissue)- and vice versa for low scores, where 'not favorable' response is having neither a pT0 or \<= pT1 predicted response.

47 participants included in the ITT analysis (n=28 on the GC arm, n=19 on the ddMVAC arm) were not evaluable for the primary COXEN analysis and therefore did not have COXEN scores generated

GC-COXEN score

Coexpression extrapolation (COXEN) score to predict tumor response to treatment with ddmVAC. COXEN algorithm is a novel approach to generate predictive gene expression models for cancer therapy response. COXEN scores(coefficient) for a participant on a therapy were categorized into low/high scores. High scores predict whether a participant has a 'favorable' response-either pT0 (complete disappearance of tumor) or downgrading to \<= pT1 (tumor invades subepithelial connective tissue)- \& vice versa for low scores, where 'not favorable' response is having neither a pT0 or \<=pT1 predicted response.

ddMVAC-COXEN score

Genitourinary Committee Statistician

To determine the relationship of GC COXEN scores to pT0, GC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT0 within the GC treatment group.

To determine the relationship of ddMVAC COXEN scores to pT0, ddMVAC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT0 within the ddMVAC treatment group.

Favorable treatment-COXEN score

Unfavorable treatment-COXEN score

Eligible participants that were evaluable for COXEN analysis

Assessment of Whether the Treatment-specific COXEN Score is Prognostic of pT0 Rate

To determine the relationship of GC COXEN scores to \<= pT1, GC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT1 or better within the GC treatment group.

To determine the relationship of ddMVAC COXEN scores to \<=pT1, ddMVAC COXEN score (dichotomous, favorable vs. unfavorable) was tested in a logistic regression model predicting the outcome of pT1 or better within the ddMVAC treatment group.

Assessment of Whether the Treatment-specific COXEN Score is Prognostic of ≤ pT1 Rate

P-value of interaction term (GCscore*treatment arm) in model predicting pT0

P-value of interaction term (GCscore*treatment arm) in logistic regression model predicting <=pT1

P-value of interaction term (MVACscore*treatment arm) in logistic regression model predicting pT0

P-value of interaction term (MVACscore*treatment arm) in logistic regression model predicting <=pT1

All Participants

Eligible participants that were evaluable for COXEN analysis. Participants in this arm were pooled to test the ability of the COXEN algorithm to distinguish between GC and ddMVAC treatment, with the assumption that there is no interaction between the COXEN score and treatment arm.

Assessment of COXEN Score as a Predictive Factor Distinguishing Between GC and ddMVAC

Pearson correlation coefficient

Spearman correlation coefficient

Correlation Between GC-and ddMVAC-COXEN Score

Pvalue of interaction term (GCscore*treatment arm) in model predicting pT0

Pvalue of interaction term (GCscore*treatment arm) in model predicting <=pT1

Pvalue of interaction term (MVACscore*treatment arm) in model predicting pT0

Pvalue of interaction term (MVACscore*treatment arm) in model predicting <=pT1

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)

Overall Survival

Pathologic T0 Rate Evaluation: Gemcitabine+Cisplatin (GC) Versus Dose-dense Methotrexate, Vinblastin, Doxorubicin, and Cisplatin (DDMVAC)

Acute kidney injury

Alanine aminotransferase increased

Anemia

Bronchial infection

Cardiac arrest

Cardiac disorders - Other, specify

Chronic kidney disease

Creatinine increased

Dehydration

Diarrhea

Dizziness

Dyspnea

Enterocolitis infectious

Erectile dysfunction

Esophagitis

Fall

Fatigue

Febrile neutropenia

Headache

Heart failure

Hematuria

Hyperglycemia

Hyperkalemia

Hypertension

Hypocalcemia

Hypokalemia

Hypomagnesemia

Hyponatremia

Hypophosphatemia

Infections and infestations - Other, specify

Insomnia

Investigations - Other, specify

Kidney infection

Lung infection

Lymphocyte count decreased

Mucositis oral

Nausea

Neutrophil count decreased

Phlebitis infective

Platelet count decreased

Proteinuria

Renal and urinary disorders - Other, specify

Sepsis

Syncope

Thromboembolic event

Tinnitus

Upper gastrointestinal hemorrhage

Urinary tract infection

Urinary tract obstruction

Vestibular disorder

Vomiting

White blood cell decreased

Participants who received at least one dose of protocol treatment, submitted toxicity data and were included in the ITT analysis.

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

ITT Analysis

Primary COXEN Analysis

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer	NCT02177695	Bladder Cancer	Gemcitabine Cisplatin Methotrexate Vinblastine Doxorubicin Filgrastim	18 Years -	SWOG Cancer Research Network
S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer	NCT02177695	Bladder Cancer	Gemcitabine Cisplatin Methotrexate Vinblastine Doxorubicin Filgrastim	18 Years -	SWOG Cancer Research Network

Spots Global Cancer Trial Database for s1314

Every month we try and update this database with for s1314 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for s1314

Every month we try and update this database with for s1314 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for s1314 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.