SWOG clinical trial number
S1314

A Randomized Phase II Study of CO-eXpression ExtrapolatioN (COXEN)-Directed Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer

Closed
Phase
Accrual
100%
Abbreviated Title
Phase II COXEN Trial for Localized Bladder Cancer
Activated
07/09/2014
Closed
12/01/2017
Participants
ALL NATIONAL CLINICAL TRIALS NETWORK MEMBERS

Research committees

Genitourinary Cancer

Treatment

Cisplatin Doxorubicin Filgrastim Gemcitabine hydrochloride Methotrexate Vinblastine Sulfate Pegfilgrastim MVAC

Other Study Materials

Eligibility Criteria Expand/Collapse

Histologically proven urothelial Ca of the bladder (mixed histology ok); Stage cT2-T4aN0M0; no prior systemic chemotherapy or previous systemic anthracyclines (intravesical anthracycline is allowed); abdominal/pelvic CT or MRI scan and chest CT scan (or x-ray) w/in 56 days prior to registration; if alk phos is above IULN or presence of suspicious bone pain (or if other clinical suspicion) then a whole body bone scan w/in 56 days prior to registration; PS = 0 or 1; 18 yrs of age or older; must not have peripheral neuropathy >/= Gr2; must not have NYHA Class III or IV heart failure or a known LVEF < 50%; must not have clinically relevant hearing impairment > Gr2; must not have hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or filgrastim/pegfilgrastim; must not have incidence of or uncontrolled medical illness that would limit the patient's ability to participate in the protocol; must not be pregnant or nursing; pts of reproductive potential must agree to use an effective contraceptive method during and for 6 months after completing protocol txt (a neg pregnancy test is required w/in 7 days prior to registration); no other prior malignancy is allowed expect for the following: adequately treated basal cell or squamous cell skin Ca, in situ cervical Ca, adequately treated Stage I or II Ca from which the patient is currently in complete remission, or any other Ca from which the patient has been disease free for 5 years. Pts with localized prostate Ca who are being followed by an active surveillance program are also eligible; pts must have tumor tissue from transurethral resection of the bladder tumor (TURBT) available for submission for COXEN testing and must agree to submit 22 FFPE slides; pt must consent (if residual tumor is present) to the submission of FFPE slides; pt must agree to submit voided urine and whole blood; pts must agree to participate in the translational medicine studies outlined in Section 18.3 of the protocol; pts must be offered participation in the ultra pure Circulating Tumor Cells (upCTCs) study.

Adequate renal, hepatic, and hematologic function w/in 28 days prior to registration:
CrCl >/= 60 mL/min; total bilirubin </= 1.5 IULN (or 2.5 x IULN w/ Gilbert's disese); SGOT(AST)/SGPT(ALT) </= 2 X IULN; ANC >/= 1500/mcL; hemoglobin >/= 9 g/dL; platelets = 100,000/mcL

Publication Information Expand/Collapse

2024

Association of Molecular Subtypes with Pathologic Response, PFS, and OS in a Phase II Study of COXEN with Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer

S Lerner;D McConkey;C Tangen;JJ Meeks;T Flaig;X Hua;S Daneshmand;A Alva;MS Lucia;D Theodorescu;A Goldkorn;M Milowsky;W Choi;R Bangs;D Gustafson;M Plets;IM Thompson Clinical Cancer Research Jan 17;30(2):444-449

PMid: PMID37966367 | PMC number: PMC10824507

DNA Damage Response Gene Alterations Predict for Neoadjuvant Chemotherapy Sensitivity in Muscle-Invasive Bladder Cancer: A Correlative Analysis of the SWOG S1314 Trial

G Iyer;C Tangen;M Sarfaty;A Regazzi;I Lee;M Fong;W Choi;C Dinney;T Flaig;I Thompson;S Lerner;D McConkey;J Rosenberg JCO Precision Oncology Nov:8:e2400287. doi: 10.1200/PO.24.00287. Epub 2024 Nov 5. 2024

Predicting clinical outcomes in the S1314-COXEN Trial using a Multimodal Deep Learning Model Integrating Histopathology, Cell Types, and Gene Expression

B Faltas;Z Bai;M Osman;M Brendel;C Tangen;T Flaig;M Plets;MS Lucia;D Theodorescu;D Gustafson;S Daneshmand;J Meeks;W Choi;C Dinney;O Elemento;S Lerner;D McConkey;F Wang ASCO GU Symposium (JAN 25-27, 2024, San Francisco, CA), oral

Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial

E Plimack;C Tangen;M Plets;R Kokate;J Xiu;C Nabhan;E Ross;E Grundy;W Choi;C Dinney;I Lee;M Fong;M Lucia;S Daneshmand;D Theodorescu;A Goldkorn;S Lerner;T Flaig;D McConkey European Urology Jul 12:S0302-2838(24)02453-9

PMid: PMID39003201

Biomarker challenges in the pursuit of personalized neoadjuvant chemotherapy for muscle-invasive bladder cancer: conclusions from SWOG S1314 [Editorial]

S Kim;M St-Laurent;P Black Translational Andrology and Urology Mar 31;13(3):458-462

PMid: PMID38590957 | PMC number: PMC10999026

2023

Long term outcomes from a phase II study of neoadjuvant chemotherapy for muscle invasive bladder cancer (SWOG S1314; NCT02177695)

T Flaig;C Tangen;S Daneshmand;A Alva;MS Lucia;D McConkey;D Theodorescu;A Goldkorn;M Milowsky;R Bangs;G MacVicar;B Bastos;J Fowles;D Gustafson;M Plets;I Thompson;S Lerner European Urology Sep;84(3):341-347

PMid: PMID37414705 | PMC number: PMC10659139

Cell-free DNA Methylation as a Predictive Biomarker of Response to Neoadjuvant Chemotherapy for Patients with Muscle-invasive Bladder Cancer in SWOG S1314

Y-T Lu;M Plets;G Morrison;A Cunha;S Cen;S Rhie;K Siegmund;S Daneshmand;D Quinn;J Meeks;S Lerner;D Petrylak;D McConkey;T Flaig;IM Thompson;A Goldkorn European Urology Oncology Apr 20;S2588-9311(23)00074-3

PMid: PMID37087309 | PMC number: PMC10587361

2022

SWOG S1314: A randomized phase II study of co-expression extrapolation (COXEN) with neoadjuvant chemotherapy for localized, muscle-invasive bladder cancer with overall survival follow up

T Flaig;C Tangen;S Daneshmand;A Alva;M Lucia;D McConkey;D Theodorescu;A Goldkorn;M Milowsky;R Bangs;G MacVicar;B Bastos;J Fowles;D Gustafson;M Plets;IM Thompson;SP Lerner J Clin Oncol 40, 2022 (suppl 6; abstr 536); ASCO Genitourinary (GU) Cancers Symposium 2022 (Feb 17-19, 2022, San Francisco, CA), poster

Association of DNA damage response (DDR) gene alterations (alts) and response to neoadjuvant cisplatin-based chemotherapy (chemo) in muscle-invasive bladder cancer (MIBC) patients (pts) enrolled onto SWOG S1314

G Iyer;C Tangen;M Sarfaty;A Regazzi;IM Thompson;D McConkey;T Flaig;J Rosenberg J Clin Oncol 40, 2022 (suppl 16; abstr 4522), poster 14; ASCO Annual Meeting (June 3-7, 2022, Chicago, IL)

Cell-free DNA methylation as a predictive biomarker of response to neoadjuvant chemotherapy for patients with muscle invasive bladder cancer in SWOG S1314

Y-T Lu;M Plets;G Morrison;A Cunha;S Cen;S Rhie;K Siegmund;S Daneshmand;D Quinn;S Lerner;D Petrylak;D McConkey;T Flaig;I Thompson;A Goldkorn J Clin Oncol 40, 2022 (suppl 16; abstr 4506), abst 4506; ASCO Annual Meeting (June 3-7, 2022, Chicago, IL), oral

S1314 Correlative analysis of ATM, RB1, ERCC2 and FANCC mutations and pathologic complete response (pT0) at cystectomy after neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC): implications for bladder preservation

E Plimack;C Tangen;M Plets;R Kokate;J Xiu;C Nabhan;E Ross;E Grundy;W Choi;C Dinney;I-L Lee;MS Lucia;T Flaig;D McConkey J Clin Oncol 40, 2022 (suppl 16; abstr 4581), poster 72; ASCO Annual Meeting (June 3-7, 2022, Chicago, IL)

Using Cell Lines To Guide Neoadjuvant Therapy in Bladder Cancer: COXEN and SWOG S1314

G Dancik;D Theodorescu European Urology Focus Mar 23;S2405-4569(22)00067-0

PMid: PMID35339415

2021

A randomized phase II study of coexpression extrapolation (COXEN) with neoadjuvant chemotherapy for bladder cancer (SWOG S1314; NCT02177695)

T Flaig;C Tangen;S Daneshmand;A Alva;S Lerner;M Lucia;D McConkey;D Theodorescu;A Goldkorn;M Milowsky;R Bangs;G MacVicor;B Bastos;J Fowles;D Gustafson;M Plets;I Thompson Clinical Cancer Research May 1;27(9):2435-2441; Feb 10;clincanres.2409.2020. doi: 10.1158/1078-0432.CCR-20-2409. Online ahead of print

PMid: PMID33568346 | PMC number: PMC8219246

2020

Association of Molecular Expression Based Subtypes with Pathologic Response in a Randomized Phase II Study of Co-Expression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer (SWOG S1314; NCT02177695)

S Lerner;D McConkey;C Tangen;J Meeks;T Flaig;X Hua;W Choi;S Daneshmand;A Alva;MS Lucia;D Theodorescu;A Goldkorn;M Milowsky;R Bangs;J Fowles;D Gustafson;I Thompson J Clin Oncol 38: 2020 (suppl; abstr 5028); American Society of Clinical Oncology 2020 Annual Meeting, poster

2019

From the other side:The patient perspective on cancer clinical trials [Review]

R Bangs;A Crispino Urologic Oncology: Seminars and Original Investigations May;37(5):331-335; Feb 7 [Epub ahead of print]

PMid: PMID29428573

SWOG S1314: A Randomized Phase II Study of Co-Expression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Localized, Muscle-Invasive Bladder Cancer

T Flaig;C Tangen;S Daneshmand;A Alva;MS Lucia;D McConkey;D Theodorescu;A Goldkorn;M Milowsky;R Bangs;G MacVicar;BR Bastos;D Gustafson;M Plets;IM Thompson J Clin Oncol 37(suppl; abstr 4506); ASCO Annual Meeting (May 31-June 4, 2019, Chicago, IL), oral

2016

Summary and recommendations from the National Cancer Institute's Clinical Trials planning meeting on novel therapeutics for non-muscle invasive bladder cancer

SP Lerner;DF Bajorin;CP Dinney;JA Efstathiou;S Groshen;NM Hahn;D Hansel;D Kwiatkowski;M O'Donnell;J Rosenberg;R Svatek;JS Abrams;H Al-Ahmadie;AB Apolo;J Bellmunt;M Callahan;EK Cha;C Drake;J Jarow;A Kamat;W Kim;M Knowles;B Mann;L Marchionni;D McConkey;L McShane;N Ramirez;A Sharabi;AH Sharpe;D Solit;CM Tangen;AT Amiri;E Van Allen;PJ West;JA Witjes;D Quale Bladder Cancer Apr 27;2(2):165-202

PMid: PMID27376138 | PMC number: PMC4927845

2014

Novel neoadjuvant therapy paradigms for bladder cancer: results from the National Cancer Center Institute Forum

C Dinney;D Hansel;D McConkey;W Shipley;M Hagan;R Dreicer;S Lerner;B Czerniak;F Waldman;S Groshen;LD True;E Petricoin;D Theodorescu;A Hruszkewycz;D Bajorin Urologic Oncology 32(8):1108-15;

PMid: PMID25443274 | PMC number: PMC4262150

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Research Committee(s)
Genitourinary Cancer
Activated
08/14/2023
Accrual
7%
Open
Phase
SWOG Clinical Trial Number
S2200