Stage III Bladder CancerPhase 3NCT00028756

Comparison of Immediate and Delayed Adjuvant Chemotherapy in Treating Patients Who Have Undergone a Radical Cystectomy for Stage III or Stage IV Transitional Cell Carcinoma of the Bladder Urothelium

A Phase 3 study testing doxorubicin hydrochloride, gemcitabine hydrochloride and vinblastine sulfate in people with Stage III Bladder Cancer and Stage IV Bladder Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Any age
Conditions the study is for: Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder
What is being tested?: doxorubicin hydrochloride, gemcitabine hydrochloride and vinblastine sulfate
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 285 participants
Where: No sites listed yet
Study dates: Oct 2001to Jul 2014
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Histologically confirmed transitional cell carcinoma of the bladder urothelium
T3-4, N1-3, M0
No pure squamous cell or adenocarcinoma tumors
No more than 90 days since prior radical cystectomy and bilateral lymphadenectomy without evidence of microscopic residual disease
Performance status - WHO 0-1
WBC at least 3,500/mm^3

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Platelet count at least 120,000/mm^3
SGOT/SGPT less than 2.5 times upper limit of normal (ULN)
Alkaline phosphatase less than 2.5 times ULN
Bilirubin normal
Glomerular filtration rate greater than 60 mL/min
No clinically significant cardiac arrhythmia
No congestive heart failure
No complete bundle branch block
No New York Heart Association class III or IV heart disease
Not pregnant or nursing
Fertile patients must use effective contraception during and for 6 months after study
Considered fit for cisplatin-containing combination chemotherapy
No clinically abnormal auditory function
No known hypersensitivity to E. coli-derived drug preparations
No grade 2 or greater peripheral neuropathy
No other prior or concurrent malignancy except adequately treated carcinoma in situ of the cervix, treated basal cell skin cancer, or treated incidental prostate cancer (pT2, Gleason score no greater than 6, and PSA less than 0.5 ng/mL)
No psychological, familial, sociological, or geographical condition that would preclude study involvement
No prior systemic chemotherapy
No prior radiotherapy to the bladder

Who cannot join

None listed.

About this study

Official title: Randomized Phase III Trial Comparing Immediate Versus Deferred Chemotherapy After Radical Cystectomy in Patients With pT3-pT4, and/or N+M0 Transitional Cell Carcinoma (TCC) of the Bladder

Randomized phase III trial to compare the effectiveness of immediate adjuvant chemotherapy with that of adjuvant chemotherapy given when the cancer returns in treating patients who have undergone a radical cystectomy for stage III or stage IV transitional cell carcinoma of the bladder urothelium. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known if adjuvant chemotherapy is more effective when given immediately after radical cystectomy (surgery to remove the bladder) or when the cancer returns.

Read the detailed description

PRIMARY OBJECTIVES:

Compare the overall and progression-free survival of patients with stage III or IV transitional cell carcinoma of the bladder urothelium treated with immediate versus deferred adjuvant chemotherapy after radical cystectomy.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, tumor status (pT1-2 vs pT3 vs pT4), and node status (node positive vs node negative with 15 or more nodes sampled vs node negative with less than 15 nodes sampled). Patients are randomized to one of two treatment arms.

ARM I: Beginning within 90 days of radical cystectomy, patients receive a total of 4 courses of adjuvant chemotherapy.

ARM II: Beginning at the time of clinical relapse, patients receive a total of 6 courses of adjuvant chemotherapy.

Patients in both arms receive one of the following chemotherapy regimens to be determined by participating center:

REGIMEN A (Classical M-VAC): Patients receive classical M-VAC comprising methotrexate IV on days 1, 15 and 22; vinblastine IV on days 2, 15, and 22; and doxorubicin IV and cisplatin IV on day 2. Courses repeat every 28 days.

REGIMEN B (High-dose M-VAC): Patients receive high-dose M-VAC comprising methotrexate IV on day 1 and vinblastine IV, doxorubicin IV, and cisplatin IV on day 2. Patients also receive filgrastim (G-CSF subcutaneously once daily on days 4-10. Courses repeat every 14 days.

REGIMEN C (Gemcitabine and cisplatin): Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 followed by cisplatin IV on day 1 or 2. Courses repeat every 28 days.

Patients are followed every 3 months for 1 year, every 6 months for 5 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK and EORTC.

Conditions: Stage III Bladder Cancer, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder
Being tested: doxorubicin hydrochloride, gemcitabine hydrochloride, vinblastine sulfate, methotrexate, cisplatin
Medical subject headings: Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

doxorubicin hydrochlorideDrug
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
gemcitabine hydrochlorideDrug
Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Given IV
vinblastine sulfateDrug
Also called 29060-LE, Exal, Velban, Velbe
Given IV
methotrexateDrug
Also called amethopterin, Folex, methylaminopterin, Mexate
Given IV
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
filgrastimBiological
Also called G-CSF, Neupogen
Given SC

Study groups in NCT00028756
Study group	Role	What they receive
Arm I (immediate chemotherapy)	Active comparator	Beginning within 90 days of radical cystectomy, patients receive a total of 4 courses of adjuvant chemotherapy. Receives: Drug: doxorubicin hydrochloride; Drug: gemcitabine hydrochloride; Drug: vinblastine sulfate; Drug: methotrexate; Drug: cisplatin; Biological: filgrastim
Arm II (deferred chemotherapy)	Experimental	Beginning at the time of clinical relapse, patients receive a total of 6 courses of adjuvant chemotherapy. Receives: Drug: doxorubicin hydrochloride; Drug: gemcitabine hydrochloride; Drug: vinblastine sulfate; Drug: methotrexate; Drug: cisplatin; Biological: filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

Duration of survival
Estimated using the Kaplan-Meier technique and compared based on a two sided logrank test with retrospective stratification for the participating cooperative group, the chemotherapy regimen, the T category and the nodal status.
Measured: 5 years
Duration of progression-free survival
Estimated using the Kaplan-Meier technique and compared based on a two sided logrank test with retrospective stratification for the participating cooperative group, the chemotherapy regimen, the T category and the nodal status.
Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2001Jul 2014

First posted27 Jan 2003 (estimated)
Study startOct 2001
Primary completionJan 2014
Study completionJul 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Stage III Bladder CancerStudies of the same condition, open and under way.
More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 285 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00028756
Sponsor's protocol ID: EORTC 30994
Other IDs: EORTC-30994, CDR0000069130, CAN-NCIC-EORTC-30994, ACOSOG-EORTC-30994, NCRI-BLADDER-EORTC-30994, UKCCCR-EORTC-30994, FNCLCC-GETUG-EORTC-30994, N02CM62212
Status last verified: Aug 2016
First submitted: 4 Jan 2002
Last updated: 2 Aug 2016
Results posted: No

Publications

Sternberg CN, Skoneczna I, Kerst JM, Albers P, Fossa SD, Agerbaek M, Dumez H, de Santis M, Theodore C, Leahy MG, Chester JD, Verbaeys A, Daugaard G, Wood L, Witjes JA, de Wit R, Geoffrois L, Sengelov L, Thalmann G, Charpentier D, Rolland F, Mignot L, Sundar S, Symonds P, Graham J, Joly F, Marreaud S, Collette L, Sylvester R; European Organisation for Research and Treatment of Cancer Genito-Urinary Cancers Group; Groupe d'Etude des Tumeurs Urogenitales; National Cancer Research Institute Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; German Association of Urologic Oncology. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015 Jan;16(1):76-86. doi: 10.1016/S1470-2045(14)71160-X. Epub 2014 Dec 11.
PubMed 25498218

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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