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

Browse trials for

• Urinary Bladder Neoplasms 1,616

Keywords

• Bladder Cancer
• Neoadjuvant Chemotherapy
• Coexpression Extrapolation
• COXEN
• S1314
• SWOG

Urinary Bladder Neoplasms

1,616 studies on the registry are indexed under Urinary Bladder Neoplasms; 421 are open to participants now.

This study's enrollment of 237 is above the median of 60 across 1,163 interventional studies indexed under Urinary Bladder Neoplasms.

Lead sponsor

SWOG Cancer Research Network is the lead sponsor of 328 studies on the registry; 37 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.

Study arms

• 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 · 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

  Drug: Cisplatin · Drug: Methotrexate · Drug: Vinblastine · Drug: Doxorubicin · Drug: Filgrastim

Interventions

• DrugGemcitabine

  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.

  Also known as: Gemzar

• DrugCisplatin

  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.

  Also known as: Platinol

• DrugMethotrexate

  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.

  Also known as: Trexall

• DrugVinblastine

  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.

  Also known as: Velban

• DrugDoxorubicin

  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.

  Also known as: Adriamycin

• DrugFilgrastim

  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.

  Also known as: Neupogen

Primary outcomes

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

   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.

   Time frame: Up to 5 years post registration

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

   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.

   Time frame: up to 5 years post-registration

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

   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.

   Time frame: up to 5 years post-registration

4. Correlation Between GC-and 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.

   Time frame: up to 5 years post-registration

Secondary outcomes

1. 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)

   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.

   Time frame: Up to 5 years post registration

2. Value of Gene Expression Profiling in Predicting Overall Survival (OS)

   5-year OS curve was estimated using the Kaplan-Meier method. Included all COXEN evaluable participants regardless of arm assignment. The report groups were favorable vs. unfavorable COXEN status.

   Time frame: Up to 5 years post registration

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

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

   Time frame: Up to 5 years post-registration

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

   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

   Time frame: Duration of treatment and follow up until death or 5 years post registration

Baseline characteristics

Publications

• Flaig TW, Tangen CM, Daneshmand S, Alva A, Lerner SP, Lucia MS, McConkey DJ, Theodorescu D, Goldkorn A, Milowsky MI, Bangs R, MacVicar GR, Bastos BR, Fowles JS, Gustafson DL, Plets M, Thompson IM Jr. A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695). Clin Cancer Res. 2021 May 1;27(9):2435-2441. doi: 10.1158/1078-0432.CCR-20-2409. Epub 2021 Feb 10. PubMed 33568346 ↗

Study documents

• Protocol, analysis plan and consent form · Jul 15, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive