Recurrent Non-Muscle Invasive Bladder CarcinomaPhase 3GAIN-BCGNCT07000084
Testing the Addition of an Anti-Cancer Drug, Gemcitabine, to Usual Treatment (BCG Alone) in People Whose Non-Muscle Invasive Bladder Cancer (NMIBC) Came Back After Prior BCG Therapy
A Phase 3 study testing BCG Solution, Biopsy of Bladder and Cystoscopy in people with Recurrent Non-Muscle Invasive Bladder Carcinoma and Stage 0a Bladder Cancer AJCC v8, run by Alliance for Clinical Trials in Oncology at 60 sites in United States.
Trial summary
This phase III trial compares the effect of adding gemcitabine to intravesical Bacillus Calmette Guerin (BCG) versus intravesical BCG alone in patients with non-muscle invasive bladder cancer that has come back after a period of improvement (recurrent). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Non-Muscle Invasive Bladder Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8
- What is being tested?
- BCG Solution, Biopsy of Bladder and Cystoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 330 participants
- Where
- 60 sitesUnited States
- Study dates
- 17 Jul 2025to 5 Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documentation of Disease: Histologic confirmation of urothelial carcinoma that is high grade Ta, high grade T1, or Tis (Tis/carcinoma in situ [CIS] only disease) within 120 days prior to randomization
- Any component of neuroendocrine carcinoma (i.e., small cell or large cell) is not allowed. Other histologic subtypes/variant histologies are allowed so long as there is a predominantly urothelial component.
- Note: Pure squamous cell carcinoma or pure adenocarcinoma without a urothelial component are not allowed
- All visible papillary lesions must be macroscopically resected by TURBT within 90 days of randomization. (Residual CIS is permitted).
- If the treating urologist did not perform the TURBT, the treating urologist must perform a cystoscopy within 45 days prior to randomization to confirm the absence of visible papillary disease
- All patients with high grade T1 must undergo a restaging TURBT within 90 days of randomization. Patients who undergo a restaging TURBT that shows no residual cancer in the specimen are still eligible for trial based on prior TURBT
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- Patients must have BCG-Exposed non muscle invasive bladder carcinoma (NMIBC), defined as recurrent high grade NMIBC within 24 months of last BCG exposure but not meeting the definition of BCG unresponsive disease
- Note: Up to 26 months from the last BCG instillation is allowed for the treating physician to perform a transurethral resection of bladder tumor (TURBT) so long as there is evidence/suspicion of recurrent disease (by positive cytology, imaging, or cystoscopy) within 24 months of last exposure to BCG.
- Note: A patient who previously met the definition of BCG unresponsive NMIBC but no longer currently meets unresponsive criteria may still enroll in this trial so long as the treating urologist believes re-treatment with BCG is a reasonable treatment option for that patient.
- BCG-exposed NMIBC criteria is defined as:
- Any high grade NMIBC recurrence within 24 months of induction only BCG, or
- A high grade papillary NMIBC (Ta/T1) recurrence between 6-24 months of last exposure to induction + maintenance BCG, or
- A high-grade CIS (with or without Ta/T1 papillary disease) recurrence within 12-24 months of last exposure to induction + maintenance BCG.
- Patient must not have BCG-unresponsive NMIBC, defined as:
- Persistent or recurrent high-grade papillary NMIBC (Ta/T1) < 6 months of "adequate" BCG, or
- A high-grade CIS (with or without Ta/T1 papillary disease) recurrence < 12 months of "adequate" BCG, or
- A high grade T1 recurrence at the first 3-month assessment from induction BCG
- "Adequate" BCG is defined as ≥5 of 6 doses of induction BCG therapy with either
- ≥ 2 of 3 doses of maintenance BCG, or
- ≥ 2 of planned 6 instillations of repeat induction BCG given within a 6 month time period
- More than one prior induction course of BCG and/or prior maintenance BCG is allowed so long as the patient does not currently met the definition of BCG unresponsive disease
- Prior treatment with any intravesical chemotherapy (both perioperative and induction course) for NMIBC is allowed, including gemcitabine either alone or in combination (ie. gemcitabine plus docetaxel) or gemcitabine delivered through a intravesical delivery system (ie. TAR-200)
- Prior treatment with any systemic or intravesical agents for NMIBC is allowed, regardless of whether it is given either alone or in prior combination with BCG (ie. Prior treatment with pembrolizumab, other immune checkpoint inhibitors, nadofaragene firadenovec, nogapendekin alfa inbakicept, cretostimogene grenadenorepvec, etc. are all allowed)
- Patients must not have a history of intolerance to BCG (ie needing to stop BCG induction or maintenance due to toxicity) or intolerance to any other intravesical therapies
- Patients must not have compromised bladder function such that they are unlikely to tolerate further intravesical therapies
- Patient must not have any prior history or current evidence of muscle-invasive (i.e., T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on radiographic imaging obtained within 120 days prior to randomization.
- The radiographic imaging includes a CT Scan or MRI of the abdomen/pelvis with intravenous contrast, with a CT or MRI urogram preferred. If a patient is unable to receive intravenous contrast due to renal function or allergy, then either a CT scan or MRI of the abdomen/pelvis without intravenous contrast is acceptable
- Patients with a history of upper tract urothelial carcinoma are allowed so long as they had localized non-muscle invasive (Ta, T1, Tis) that has been definitively treated with surgery (nephroureterectomy or ureterectomy) with at least one post-treatment disease assessment imaging study that demonstrates no evidence of residual upper tract disease
- Patients with a history of, or current evidence of, non-invasive (Ta/Tis) urothelial carcinoma of the prostatic urethra are eligible so long as a transurethral resection of prostate (TURP) is performed before enrollment and there is prostatic glandular tissue without evidence of lamina propria invasion or prostatic stromal invasion
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Age ≥ 18 years
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Not pregnant and not nursing, Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
- has achieved menarche at some point
- has not undergone a hysterectomy or bilateral oophorectomy
- has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Who cannot join
None listed.
Trial locations and contacts
60 sites in 1 country. Contact the study team or a site near you to ask about taking part.
60 sites in 1 country
United States60 sites, 60 recruiting
- Recruiting
Community Hospital of Anaconda
Anaconda, Montana, 59711
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
IU Health West Hospital
Avon, Indiana, 46123
Site Public Contact, 317-278-5632, iutrials@iu.edu
Hristos Kaimakliotis
- Recruiting
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Site Public Contact, 410-955-8804, jhcccro@jhmi.edu
Max Kates
- Recruiting
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
Billings Clinic Cancer Center
Billings, Montana, 59101
Site Public Contact, 800-996-2663, research@billingsclinic.org
John M. Schallenkamp
- Recruiting
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Site Public Contact, gingerreeves@uabmc.edu
Charles C. Peyton
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Site Public Contact, 617-724-5200
Filipe De Carvalho
- Recruiting
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Site Public Contact, 800-767-9355, askroswell@roswellpark.org
Qiang J. Li
- Recruiting
Lahey Clinic
Burlington, Massachusetts, 01805
Site Public Contact, 781-744-3421, lhmc-cancer-clinical-trials@lahey.org
Matthew B. Clements
- Recruiting
IU Health North Hospital
Carmel, Indiana, 46032
Site Public Contact, 317-278-5632, iutrials@iu.edu
Hristos Kaimakliotis
- Recruiting
Ralph H Johnson VA Medical Center
Charleston, South Carolina, 29401
Site Public Contact, 843-789-7020, ashley.salvo@va.gov
Stephen J. Savage
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Site Public Contact, 843-792-9321, hcc-clinical-trials@musc.edu
Robert L. Grubb
- Recruiting
Memorial Hospital of Laramie County
Cheyenne, Wyoming, 82001
Site Public Contact, 773-702-9171, protocols@AllianceNCTN.org
John M. Schallenkamp
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Site Public Contact, 312-695-1301, cancer@northwestern.edu
Joshua J. Meeks
- Recruiting
University of Illinois
Chicago, Illinois, 60612
Site Public Contact, 312-355-3046
Daniel Moreira
- Recruiting
Billings Clinic-Cody
Cody, Wyoming, 82414
Site Public Contact, 800-996-2663, research@billingsclinic.org
John M. Schallenkamp
- Recruiting
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Debasish Sundi
- Recruiting
Memorial Sloan Kettering Commack
Commack, New York, 11725
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
Geisinger Medical Center
Danville, Pennsylvania, 17822
Site Public Contact, 570-271-5251, cancerresearch@geisinger.edu
Tullika Garg
- Recruiting
Geisinger Cancer Center Dickson City
Dickson City, Pennsylvania, 18519
Site Public Contact, 877-204-6081, cancerresearch@geisinger.edu
Tullika Garg
- Recruiting
Fairbanks Memorial Hospital
Fairbanks, Alaska, 99701
Site Public Contact, 907-458-3043, Veronica.Stevenson@foundationhealth.org
John M. Schallenkamp
- Recruiting
FMH James M Stockman Cancer Institute
Frederick, Maryland, 21702
Site Public Contact, 301-668-7043
Heather Chalfin
- Recruiting
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Site Public Contact, 352-273-8010
Paul L. Crispen
- Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
Site Public Contact, 602-747-9738
Chinedu Mmeje
- Recruiting
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Great Falls Clinic
Great Falls, Montana, 59405
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Site Public Contact, 551-996-2897
Nitin Yerram
- Recruiting
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
Hi-Line Sletten Cancer Center
Havre, Montana, 59501
Site Public Contact, 773-702-9171, protocols@AllianceNCTN.org
John M. Schallenkamp
- Recruiting
Benefis Helena Specialty Center
Helena, Montana, 59601
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Site Public Contact, 317-278-5632, iutrials@iu.edu
Hristos Kaimakliotis
- Recruiting
IU Health Methodist Hospital
Indianapolis, Indiana, 46202
Site Public Contact, 317-278-5632, iutrials@iu.edu
Hristos Kaimakliotis
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Michael Daneshvar
- Recruiting
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Site Public Contact, 855-776-0015
Mark D. Tyson
- Recruiting
Logan Health Medical Center
Kalispell, Montana, 59901
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Geisinger Medical Oncology-Lewisburg
Lewisburg, Pennsylvania, 17837
Site Public Contact, 570-523-9200, cancerresearch@geisinger.edu
Tullika Garg
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Site Public Contact, 708-226-4357
Michael E. Woods
- Recruiting
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
Melrose Park, Illinois, 60160
Site Public Contact, 708-450-4554
Michael E. Woods
- Recruiting
Mary Bird Perkins Cancer Center - Metairie
Metairie, Louisiana, 70002
Site Public Contact, 504-584-6990
Scott E. Delacroix
- Recruiting
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
Community Medical Center
Missoula, Montana, 59804
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
Veterans Affairs New York Harbor Healthcare System-Manhattan Campus
New York, New York, 10010
Site Public Contact, John.hay@va.gov
LaMont Barlow
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
Kelly L. Stratton
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Michael Daneshvar
- Recruiting
Lahey Clinic Peabody
Peabody, Massachusetts, 01960
Site Public Contact, 781-744-3421, lhmc-cancer-clinical-trials@lahey.org
Matthew B. Clements
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Site Public Contact, 215-728-4790
Andres F. Correa
- Recruiting
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
Site Public Contact, 855-776-0015
Mark D. Tyson
- Recruiting
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Renown Regional Medical Center
Reno, Nevada, 89502
Site Public Contact, 775-982-5050, Renown-CRD@renown.org
Shi-Ming Tu
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Alexander P. Kenigsberg
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Site Public Contact, 855-776-0015
Mark D. Tyson
- Recruiting
Fox Chase Cancer Center-Rockledge
Rockledge, Pennsylvania, 19046
Site Public Contact, 888-823-5923, ctsucontact@westat.com
Andres F. Correa
- Recruiting
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Site Public Contact, 406-969-6060, mccinfo@mtcancer.org
John M. Schallenkamp
- Recruiting
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
Site Public Contact, 212-639-7592
Eugene J. Pietzak
- Recruiting
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Site Public Contact, 202-243-2373, jquiver1@jhmi.edu
Max Kates
- Recruiting
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Site Public Contact, 570-271-5251, HemonCCTrials@geisinger.edu
Tullika Garg
About this study
Official title: GAIN-BCG: Gemcitabine Alternating With INtravesical BCG Randomized Against BCG Alone for Patients With Recurrent High Grade Non-Muscle Invasive Bladder Cancer
This phase III trial compares the effect of adding gemcitabine to intravesical Bacillus Calmette Guerin (BCG) versus intravesical BCG alone in patients with non-muscle invasive bladder cancer that has come back after a period of improvement (recurrent). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Intravesical BCG is a solution containing the live BCG bacteria that is placed in the bladder via a catheter (intravesical). When the solution comes into direct contact with the bladder wall, it stimulates the body's immune system which kills tumor cells. Giving gemcitabine with intravesical BCG may kill more tumor cells in patients with recurrent non-muscle invasive bladder cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To compare high-grade recurrence-free-survival between treated with gemcitabine with BCG (GemBCG) compared to those treated with BCG alone.
SECONDARY OBJECTIVES:
- To compare the proportion of patients who remain high grade cancer free on initial post-treatment cystoscopic biopsies/transurethral resection of bladder tumor (TURBT) (week 13/month 3) between those treated with GemBCG compared to those treated with BCG alone.
II. To compare the 6-month (Week 25) complete response rate and the complete response durability between patients treated with GemBCG compared to those treated with BCG alone among patients with pre-treatment CIS.
III. To compare the time to recurrence of any-grade bladder cancer between patients treated with GemBCG compared those treated with BCG alone.
IV. To compare the progression-free-survival between patients treated with GemBCG compared to those treated with BCG alone.
- To compare the cystectomy-free-survival between patients treated with GemBCG compared to those treated with BCG alone.
VI. To compare the proportion of patients free from BCG-unresponsive NMIBC between those treated with GemBCG compared to those treated with BCG alone.
VII. To determine the safety of and toxicity associated with GemBCG treatment relative to that of BCG treatment alone.
EXPLORATORY OBJECTIVE:
- To collect tumor tissue/bladder biopsies, blood, and urine samples for biobanking that will enable future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive BCG intravesically over 2 hours once per week (QW) for 6 weeks. 2-6 weeks after completing endoscopic assessment, patients receive BCG over 2 hours QW for 3 weeks at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, computed tomography (CT) scan/ magnetic resonance imaging (MRI) and blood and urine sample collection throughout the study.
ARM B: Patients receive gemcitabe intravesically over 1 hour twice weekly on weeks 1 and 10 and once weekly on weeks 4 and 7. Patients also receive BCG intravesically over 2 hours QW on weeks 2, 3, 6, 8 and 9. 2-6 weeks after completing endoscopic assessment, patients receive gemcitable intravesically over 1 hour on week 1 and BCG intravesically over 2 hours on week 2-4 at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study.
After completion of study treatment, patients are followed every 3 months for 2 years, then every 6 months for 3 years up to 5 years from randomization.
- Conditions
- Recurrent Non-Muscle Invasive Bladder Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8
- Being tested
- BCG Solution, Biopsy of Bladder, Cystoscopy, Computed Tomography, Magnetic Resonance Imaging
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG SolutionBiological
Also called Bacillus Calmette Guerin Solution
Given intravesically
Biopsy of BladderProcedure or surgery
Also called Bladder Biopsy
Undergo bladder biopsy
CystoscopyProcedure or surgery
Undergo cystoscopy
Computed TomographyProcedure or surgery
Also called CAT Scan, CT Scan
Undergo CT Scan
Magnetic Resonance ImagingProcedure or surgery
Also called MRI
Undergo MRI
Biospecimen CollectionProcedure or surgery
Undergo blood and urine sample collection
Transurethral Resection of Bladder TumorProcedure or surgery
Also called TURBT
Undergo TURBT
GemcitabineDrug
Given intravesically
| Study group | Role | What they receive |
|---|---|---|
| Arm A (BCG) | Active comparator | Patients receive BCG intravesically over 2 hours QW for 6 weeks. 2-6 weeks after completing endoscopic assessment, patients receive BCG over 2 hours QW for 3 weeks at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study. Receives: Biological: BCG Solution; Procedure: Biopsy of Bladder; Procedure: Cystoscopy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Transurethral Resection of Bladder Tumor |
| Arm B (BCG and gemcitabine) | Experimental | Patients receive gemcitabe intravesically over 1 hour twice weekly on weeks 1 and 10 and once weekly on weeks 4 and 7. Patients also receive BCG intravesically over 2 hours QW on weeks 2, 3, 6, 8 and 9. 2-6 weeks after completing endoscopic assessment, patients receive gemcitable intravesically over 1 hour on week 1 and BCG intravesically over 2 hours on week 2-4 at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study. Receives: Biological: BCG Solution; Procedure: Biopsy of Bladder; Procedure: Cystoscopy; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Transurethral Resection of Bladder Tumor; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
High Grade Recurrence-free survival (HG-RFS)
HG-RFS will be calculated from randomization until the detection of a high-grade bladder cancer recurrence (biopsy proven intravesical recurrence or distant metastasis), cystectomy, or death, whichever occurs first. Patients who are alive and without documented high-grade recurrence will be censored at the time of last disease evaluation. HG-RFS will be compared between the two study arms using a stratified log-rank test. The treatment effect will be estimated with a hazard ratio (HR) and corresponding 95% confidence interval obtained from a stratified Cox model with treatment group (
Measured: Up to 5 years
Secondary outcomes (8)
High-grade cancer free at 3 months
A patient will be classified as being cancer free if no high-grade bladder cancer is detected upon a cystoscopic biopsy (± transurethral resection of bladder tumor [TURBT]). This will be calculated as the number of patients who underwent cystoscopic biopsy with or without TURBT at 3 months and no high-grade cancer was detected, divided by the total number of patients.
Measured: at 3 months
6-month Complete Response
Complete response rate will be determined among patients who had carcinoma in situ (CIS) at baseline. Patients will be classified as having a complete response at 6 months if there is no biopsy-proven high grade bladder cancer detected based on a cystoscopy and urinary cytology (± biopsy/TURBT). This will be calculated as the number of patients who had CIS at baseline and who had no evidence of disease at 6-months, divided by the total number of patients who had CIS at baseline. The proportion of patients who remain with a complete response will be compared between the two arms with a chi-square test or Fisher's exact test.
Measured: At 6 months
Durability of Response
- Durability of the response will be determined only in the patients who had CIS at baseline and had a complete response at 6 months. This will be measured as time from the 6-month evaluation until documented disease recurrence, censoring patients without disease recurrence at time of death or at last disease evaluation, whichever is last. The durability of response will be compared between the two treatment groups using a log-rank test, and Kaplan-Meier estimators will be used to determine the median durability.
Measured: Up to 5 years
Recurrence-free survival
Recurrence-free survival will be calculated as the time from randomization until the detection of any grade bladder cancer, censoring those without documented disease recurrence at time of last disease evaluation or death, whichever occurs last. This will be compared between the two treatment arms using a stratified log-rank test. An estimate of the outcome differences between the arms will be made with a HR and 95% confidence interval generated by a stratified Cox model.
Measured: Up to 5 years
Progression-free survival
Progression-free survival will be calculated as the time from randomization until disease progression, defined as development of muscle invasive disease (stage greater than or equal to T2), lymph node or distant metastasis, or death without documented disease progression. This will be compared between the two treatment arms using a stratified log-rank test. An estimate of the outcome differences between the arms will be made with a HR and 95% confidence interval generated by a stratified Cox model.
Measured: up to 5 years
Cystectomy-free survival
Cystectomy-free survival will be defined as the time from randomization until the patient undergoes a cystectomy, censoring patients without a cystectomy at last follow-up or death, whichever is last. This will be compared between the two treatment arms using a stratified log-rank test. An estimate of the outcome differences between the arms will be made with a HR and 95% confidence generated by a stratified Cox model.
Measured: up to 5 years
• Bacille Calmette Guerin (BCG)-unresponsive non muscle invasive bladder cancer free survival
BCG unresponsive NMIBC free survival will be defined as time from randomization until the patient develops BCG unresponsive NMIBC, defined as persistent or recurrent high-grade papillary NMIBC (Ta/T1) <6 months of "adequate" BCG (≥5 of 6 plus an additional ≥2 doses of BCG) or CIS (with or without Ta/T1 papillary disease) recurrence <12 months of "adequate" BCG (≥5 of 6 plus an additional ≥2 doses of BCG) or High Grade T1 at week 13 (month 3) assessment. Patients who do not develop BCG-unresponsive NMIBC will be censored at the time of their last follow-up or death, whichever is last. This will be compared between the two treatment arms using a stratified log-rank test. An estimate of the outcome differences between the arms will be made with a HR and 95% confidence interval generated by a stratified Cox model.
Measured: up to 5 years
Rate of Grade 3+ Adverse Events
- Adverse events will be collected and graded according to the NCI Common Terminology Criteria for Adverse Events version 5.0. The number (percent) of patients that experience each grade 3+ adverse event will be summarized by treatment arm. In addition, the number (percent) of patients that experience a grade 3+, grade 4+, and grade 5 adverse event will be summarized by treatment arm.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2025
- Study start17 Jul 2025
- Primary completion5 Jun 2028 (estimated)
- Study completion5 Dec 2028 (estimated)
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 Recurrent Non-Muscle Invasive Bladder CarcinomaStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe 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
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Eugene Pietzak, MD, Study chair, Alliance for Clinical Trials in Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07000084
- Sponsor's protocol ID
- A032303
- Other IDs
- NCI-2025-02655
- Acronym
- GAIN-BCG
- Status last verified
- Oct 2026
- First submitted
- 23 May 2025
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gaffney CD, Alam SM, Wald G, Sjoberg D, Eichholz J, Sarungbam J, D'Souza N, Lavery J, Hernandez C, Tomerlein M, Zagajeski P, Hildreth KW, Donat S, Smith R, Donahue T, Goh A, Bochner B, Al-Ahmadie H, Pietzak E. A Phase I Clinical Trial of Chemoimmunotherapy with Alternating Intravesical Gemcitabine and Bacillus Calmette-Guerin (GemBCG) for BCG-Exposed High-Grade Non-Muscle-Invasive Bladder Cancer. J Urol. 2026 Oct 1:101097JU0000000000005324. doi: 10.1097/JU.0000000000005324. Online ahead of print.
PubMed 42821609
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GAIN-BCG: Gemcitabine Alternating With INtravesical BCG Randomized Against BCG Alone for Patients With Recurrent High Grade Non-Muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT07000084
- Acronym / sponsor ID
- GAIN-BCG / A032303
- Conditions
- Recurrent Non-Muscle Invasive Bladder Carcinoma, Stage 0a Bladder Cancer AJCC v8, Stage I Bladder Cancer AJCC v8
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 330 participants (estimated)
- Lead sponsor
- Alliance for Clinical Trials in OncologyUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 17 Jul 2025 (actual)
- Primary completion
- 5 Jun 2028 (estimated)
- Study completion
- 5 Dec 2028 (estimated)
- First posted
- 31 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase III trial compares the effect of adding gemcitabine to intravesical Bacillus Calmette Guerin (BCG) versus intravesical BCG alone in patients with non-muscle invasive bladder cancer that has come back after a period of improvement (recurrent). Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Intravesical BCG is a solution containing the live BCG bacteria that is placed in the bladder via a catheter (intravesical). When the solution comes into direct contact with the bladder wall, it stimulates the body's immune system which kills tumor cells. Giving gemcitabine with intravesical BCG may kill more tumor cells in patients with recurrent non-muscle invasive bladder cancer.
Detailed description
PRIMARY OBJECTIVE:
- To compare high-grade recurrence-free-survival between treated with gemcitabine with BCG (GemBCG) compared to those treated with BCG alone.
SECONDARY OBJECTIVES:
- To compare the proportion of patients who remain high grade cancer free on initial post-treatment cystoscopic biopsies/transurethral resection of bladder tumor (TURBT) (week 13/month 3) between those treated with GemBCG compared to those treated with BCG alone.
II. To compare the 6-month (Week 25) complete response rate and the complete response durability between patients treated with GemBCG compared to those treated with BCG alone among patients with pre-treatment CIS.
III. To compare the time to recurrence of any-grade bladder cancer between patients treated with GemBCG compared those treated with BCG alone.
IV. To compare the progression-free-survival between patients treated with GemBCG compared to those treated with BCG alone.
- To compare the cystectomy-free-survival between patients treated with GemBCG compared to those treated with BCG alone.
VI. To compare the proportion of patients free from BCG-unresponsive NMIBC between those treated with GemBCG compared to those treated with BCG alone.
VII. To determine the safety of and toxicity associated with GemBCG treatment relative to that of BCG treatment alone.
EXPLORATORY OBJECTIVE:
- To collect tumor tissue/bladder biopsies, blood, and urine samples for biobanking that will enable future correlative studies.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive BCG intravesically over 2 hours once per week (QW) for 6 weeks. 2-6 weeks after completing endoscopic assessment, patients receive BCG over 2 hours QW for 3 weeks at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, computed tomography (CT) scan/ magnetic resonance imaging (MRI) and blood and urine sample collection throughout the study.
ARM B: Patients receive gemcitabe intravesically over 1 hour twice weekly on weeks 1 and 10 and once weekly on weeks 4 and 7. Patients also receive BCG intravesically over 2 hours QW on weeks 2, 3, 6, 8 and 9. 2-6 weeks after completing endoscopic assessment, patients receive gemcitable intravesically over 1 hour on week 1 and BCG intravesically over 2 hours on week 2-4 at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study.
After completion of study treatment, patients are followed every 3 months for 2 years, then every 6 months for 3 years up to 5 years from randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (BCG) | Active comparator | Biological: BCG Solution, Procedure: Biopsy of Bladder, Procedure: Cystoscopy, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Biospecimen Collection, Procedure: Transurethral Resection of Bladder TumorPatients receive BCG intravesically over 2 hours QW for 6 weeks. 2-6 weeks after completing endoscopic assessment, patients receive BCG over 2 hours QW for 3 weeks at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study. |
| Arm B (BCG and gemcitabine) | Experimental | Biological: BCG Solution, Procedure: Biopsy of Bladder, Procedure: Cystoscopy, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Procedure: Biospecimen Collection, Procedure: Transurethral Resection of Bladder Tumor, Drug: GemcitabinePatients receive gemcitabe intravesically over 1 hour twice weekly on weeks 1 and 10 and once weekly on weeks 4 and 7. Patients also receive BCG intravesically over 2 hours QW on weeks 2, 3, 6, 8 and 9. 2-6 weeks after completing endoscopic assessment, patients receive gemcitable intravesically over 1 hour on week 1 and BCG intravesically over 2 hours on week 2-4 at month 3, 6 and 12 in the absence of disease progression or unacceptable toxicity. Patients undergo bladder biopsy, TURBT, cystoscopy, CT scan/MRI and blood and urine sample collection throughout the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (36 listed)
- Documentation of Disease: Histologic confirmation of urothelial carcinoma that is high grade Ta, high grade T1, or Tis (Tis/carcinoma in situ [CIS] only disease) within 120 days prior to randomization
- Any component of neuroendocrine carcinoma (i.e., small cell or large cell) is not allowed. Other histologic subtypes/variant histologies are allowed so long as there is a predominantly urothelial component.
- All visible papillary lesions must be macroscopically resected by TURBT within 90 days of randomization. (Residual CIS is permitted).
- All patients with high grade T1 must undergo a restaging TURBT within 90 days of randomization. Patients who undergo a restaging TURBT that shows no residual cancer in the specimen are still eligible for trial based on prior TURBT
- Patients must have BCG-Exposed non muscle invasive bladder carcinoma (NMIBC), defined as recurrent high grade NMIBC within 24 months of last BCG exposure but not meeting the definition of BCG unresponsive disease
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG SolutionAlso: Bacillus Calmette Guerin SolutionGiven intravesically | Biological | Arm A (BCG), Arm B (BCG and gemcitabine) |
| Biopsy of BladderAlso: Bladder BiopsyUndergo bladder biopsy | Procedure or surgery | Arm A (BCG), Arm B (BCG and gemcitabine) |
| CystoscopyUndergo cystoscopy | Procedure or surgery | Arm A (BCG), Arm B (BCG and gemcitabine) |
| Computed TomographyAlso: CAT Scan, CT ScanUndergo CT Scan | Procedure or surgery | Arm A (BCG), Arm B (BCG and gemcitabine) |
| Magnetic Resonance ImagingAlso: MRIUndergo MRI | Procedure or surgery | Arm A (BCG), Arm B (BCG and gemcitabine) |
| Biospecimen CollectionUndergo blood and urine sample collection | Procedure or surgery | Arm A (BCG), Arm B (BCG and gemcitabine) |
| Transurethral Resection of Bladder TumorAlso: TURBTUndergo TURBT | Procedure or surgery | Arm A (BCG), Arm B (BCG and gemcitabine) |
| GemcitabineGiven intravesically | Drug | Arm B (BCG and gemcitabine) |
Primary outcome
High Grade Recurrence-free survival (HG-RFS)
Time frame: Up to 5 years
HG-RFS will be calculated from randomization until the detection of a high-grade bladder cancer recurrence (biopsy proven intravesical recurrence or distant metastasis), cystectomy, or death, whichever occurs first. Patients who are alive and without documented high-grade recurrence will be censored at the time of last disease evaluation. HG-RFS will be compared between the two study arms using a stratified log-rank test. The treatment effect will be estimated with a hazard ratio (HR) and corresponding 95% confidence interval obtained from a stratified Cox model with treatment group (
8 secondary outcomes
High-grade cancer free at 3 months
Time frame: at 3 months
6-month Complete Response
Time frame: At 6 months
Durability of Response
Time frame: Up to 5 years
Recurrence-free survival
Time frame: Up to 5 years
Progression-free survival
Time frame: up to 5 years
Cystectomy-free survival
Time frame: up to 5 years
• Bacille Calmette Guerin (BCG)-unresponsive non muscle invasive bladder cancer free survival
Time frame: up to 5 years
Rate of Grade 3+ Adverse Events
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Derived from this study: PubMed 42821609Gaffney CD, Alam SM, Wald G, Sjoberg D, Eichholz J, Sarungbam J, D'Souza N, Lavery J, Hernandez C, Tomerlein M, Zagajeski P, Hildreth KW, Donat S, Smith R, Donahue T, Goh A, Bochner B, Al-Ahmadie H, Pietzak E. A Phase I Clinical Trial of Chemoimmunotherapy with Alternating Intravesical Gemcitabine and Bacillus Calmette-Guerin (GemBCG) for BCG-Exposed High-Grade Non-Muscle-Invasive Bladder Cancer. J Urol. 2026 Oct 1:101097JU0000000000005324. doi: 10.1097/JU.0000000000005324. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eugene Pietzak, MD study chair
Alliance for Clinical Trials in Oncology
60 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BCG Solution, Biopsy of Bladder and Cystoscopy in people with Recurrent Non-Muscle Invasive Bladder Carcinoma and Stage 0a Bladder Cancer AJCC v8, run by Alliance for Clinical Trials in Oncology at 60 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 36 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 60 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aishwarya Vijendran ((773) 702-9171, guprotocols@alliancenctn.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
High Grade Recurrence-free survival (HG-RFS) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07000084, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.