Bladder Cancer
Conditions
Keywords
CISPLATIN, GEMCITABINE, GM-CSF, radical cystectomy, 12-071
Brief summary
The purpose of this study is to find out if standard chemotherapy (gemcitabine and cisplatin) given on a dose-dense treatment schedule (with less time between treatments) can help shrink the tumor better than standard chemotherapy given on a standard treatment schedule before the patient undergoes surgery for bladder cancer.
Interventions
Patients will receive six cycles of GC administered every 14 days. Gemcitabine 2,500 mg/m2 will be administered intravenously on day 1 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 2 of a 14 days cycle (with Peg GCSF). A total of six cycles of therapy will be administered followed by radical cystectomy with bilateral pelvic lymph node dissection (PLND)
Sponsors
University of North Carolina, Chapel Hill
New York University
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Muscle invasive urothelial carcinoma of the bladder histologically confirmed at MSKCC or participating site ((Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or EUA.) * Clinical stage T2-T4a N0/X M0 disease * Medically appropriate candidate for radical cystectomy, as per MSKCC or participating site * Karnofsky Performance Status ≥ 70% * Age ≥ 18 years of age * Required Initial Laboratory Values: * Absolute Neutrophil Count ≥ 1000 cells/mm3 * Platelets ≥ 100,000 cells/mm3 * Hemoglobin ≥ 9.0g/dL * Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution * Alkaline phosphatase ≤ 2.5 x ULN for the institution * Serum creatinine ≤ 1.5 mg/dL * Estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 using the CKD-EPI equation: eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age * x 1.018 \[if female\] x 1.159 \[if black\] Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1 * If female of childbearing potential, pregnancy test is negative
Exclusion criteria
* Prior systemic chemotherapy (prior intravesical therapy is allowed) * Prior radiation therapy to the bladder * Evidence of NYHA functional class III or IV heart disease * Serious intercurrent medical or psychiatric illness, including serious active infection * Preexisting sensory grade ≥ 2 neuropathy * Preexisting grade ≥ 2 hearing loss * Major surgery or radiation therapy \< 4 weeks of starting study treatment * Concomitant use of any other investigational drugs * Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack * Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2 * Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection * Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. QOL, are allowed * Pregnancy or breast-feeding. Patients must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response Rate | 1 year | Defined as the absence of muscle invasive carcinoma (\<pT2 disease) and the absence of lymph node metastases (N0) on the final cystectomy specimen. Pathologists will assess surgical specimens systematically using criteria agreed upon for all conventional neoadjuvant treatment based on the AJCC TNM staging system. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Toxicity | 1 year | Toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. |
| 2 Year Recurrence Free Survival (RFS) Rate for Responders | 2 years | Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method. |
| 2 Year Recurrence Free Survival (RFS) Rate for Nonresponders | 2 years | Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine and Cisplatin (DD GC) This is a Multicenter Phase II study of dose-dense (DD) gemcitabine and cisplatin (GC) neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy.
Gemcitabine and Cisplatin (DD GC): Patients will receive six cycles of GC administered every 14 days.
Gemcitabine 2,500 mg/m2 will be administered intravenously on day 1 and cisplatin 35 mg/m2 will be administered intravenously on days 1 and 2 of a 14 days cycle (with Peg GCSF). A total of six cycles of therapy will be administered followed by radical cystectomy with bilateral pelvic lymph node dissection (PLND) | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not receive treatment | 2 |
Baseline characteristics
| Characteristic | Gemcitabine and Cisplatin (DD GC) |
|---|---|
| Age, Continuous | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Region of Enrollment United States | 51 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 51 |
| other Total, other adverse events | 51 / 51 |
| serious Total, serious adverse events | 17 / 51 |
Outcome results
Primary
Pathologic Response Rate
Defined as the absence of muscle invasive carcinoma (\<pT2 disease) and the absence of lymph node metastases (N0) on the final cystectomy specimen. Pathologists will assess surgical specimens systematically using criteria agreed upon for all conventional neoadjuvant treatment based on the AJCC TNM staging system.
Time frame: 1 year
Population: 5 participants who completed 3 or more cycles of treatment did not undergo radical cystectomy: 1 refused surgery, 1 developed metastatic progression after 4 cycles, 1 withdrew consent, 1 was lost to follow-up, and 1 patient was incidentally diagnosed with moyamoya and discontinued the study because of the risk for vascular thrombotic events
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin (DD GC) | Pathologic Response Rate | 57 percentage of participants |
Secondary
2 Year Recurrence Free Survival (RFS) Rate for Nonresponders
Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.
Time frame: 2 years
Population: 20 out of 46 total participants were responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin (DD GC) | 2 Year Recurrence Free Survival (RFS) Rate for Nonresponders | 52 percentage of participants |
Secondary
2 Year Recurrence Free Survival (RFS) Rate for Responders
Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.
Time frame: 2 years
Population: 26 out of 46 total participants were responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine and Cisplatin (DD GC) | 2 Year Recurrence Free Survival (RFS) Rate for Responders | 95 percentage of participants |
Secondary
Number of Participants With Toxicity
Toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gemcitabine and Cisplatin (DD GC) | Number of Participants With Toxicity | 51 Participants |