Trial Outcomes & Findings for Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer (NCT NCT01589094)

Last Updated: 2019-10-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

1 year

Results posted on

2019-10-02

Participant Flow

Participant milestones

Participant milestones
Measure	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)
Overall Study STARTED	51
Overall Study COMPLETED	49
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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)
Overall Study Did not receive treatment	2

Baseline Characteristics

Neoadjuvant Dose Dense Gemcitabine and Cisplatin (DD GC) In Patients With Muscle-Invasive Bladder Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Gemcitabine and Cisplatin (DD GC) n=51 Participants 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)
Age, Continuous	64 years n=93 Participants
Sex: Female, Male Female	9 Participants n=93 Participants
Sex: Female, Male Male	42 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants
Race (NIH/OMB) White	46 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
Region of Enrollment United States	51 Participants n=93 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin (DD GC) n=46 Participants 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)
Pathologic Response Rate	57 percentage of participants Interval 42.0 to 70.0

SECONDARY outcome

Timeframe: 1 year

Toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin (DD GC) n=51 Participants 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)
Number of Participants With Toxicity	51 Participants

SECONDARY outcome

Timeframe: 2 years

Population: 26 out of 46 total participants were responders.

Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin (DD GC) n=26 Participants 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)
2 Year Recurrence Free Survival (RFS) Rate for Responders	95 percentage of participants

SECONDARY outcome

Timeframe: 2 years

Population: 20 out of 46 total participants were responders.

Defined as the time from treatment initiation to disease progression, local-regional or metastatic recurrence, or death analyzed using the Kaplan Meier method.

Outcome measures

Outcome measures
Measure	Gemcitabine and Cisplatin (DD GC) n=20 Participants 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)
2 Year Recurrence Free Survival (RFS) Rate for Nonresponders	52 percentage of participants

Adverse Events

Gemcitabine and Cisplatin (DD GC)

Serious events: 17 serious events

Other events: 51 other events

Deaths: 7 deaths

Serious adverse events

Serious adverse events
Measure	Gemcitabine and Cisplatin (DD GC) n=51 participants at risk 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)
Gastrointestinal disorders Abdominal Pain	3.9% 2/51 • Within 30 days of study treatment, an average of 1 year
Investigations Creatinine Increased	3.9% 2/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Dehydration	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year
General disorders Fever	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Cardiac disorders Heart failure	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Renal and urinary disorders Hematuria	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Infections and infestations Infections and infestations - Other	3.9% 2/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Nausea	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Infections and infestations Pelvic infection	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Injury, poisoning and procedural complications Postoperative hemorrhage	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Nervous system disorders Syncope	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Vascular disorders Thromboembolic event	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Nervous system disorders Transient ischemic attacks	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Renal and urinary disorders Urinary retention	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Infections and infestations Urinary tract infection	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Injury, poisoning and procedural complications Vascular access complication	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Vomiting	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year
Infections and infestations Wound infection	2.0% 1/51 • Within 30 days of study treatment, an average of 1 year

Other adverse events

Other adverse events
Measure	Gemcitabine and Cisplatin (DD GC) n=51 participants at risk 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)
Blood and lymphatic system disorders Anemia	86.3% 44/51 • Within 30 days of study treatment, an average of 1 year
General disorders Fatigue	80.4% 41/51 • Within 30 days of study treatment, an average of 1 year
Investigations Platelet count decreased	64.7% 33/51 • Within 30 days of study treatment, an average of 1 year
Investigations Alkaline phosphatase increased	62.7% 32/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Nausea	62.7% 32/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hyperglycemia	52.9% 27/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Constipation	43.1% 22/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hypomagnesemia	41.2% 21/51 • Within 30 days of study treatment, an average of 1 year
Skin and subcutaneous tissue disorders Alopecia	39.2% 20/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hypocalcemia	33.3% 17/51 • Within 30 days of study treatment, an average of 1 year
Investigations Creatinine increased	31.4% 16/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hypoalbuminemia	29.4% 15/51 • Within 30 days of study treatment, an average of 1 year
Nervous system disorders Peripheral sensory neuropathy	27.5% 14/51 • Within 30 days of study treatment, an average of 1 year
Ear and labyrinth disorders Tinnitus	27.5% 14/51 • Within 30 days of study treatment, an average of 1 year
Nervous system disorders Headache	23.5% 12/51 • Within 30 days of study treatment, an average of 1 year
Nervous system disorders Dysgeusia	21.6% 11/51 • Within 30 days of study treatment, an average of 1 year
Renal and urinary disorders Urinary frequency	21.6% 11/51 • Within 30 days of study treatment, an average of 1 year
Investigations Alanine aminotransferase increased	19.6% 10/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Diarrhea	19.6% 10/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Mucositis oral	19.6% 10/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Vomiting	19.6% 10/51 • Within 30 days of study treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Dyspnea	17.6% 9/51 • Within 30 days of study treatment, an average of 1 year
General disorders Edema limbs	15.7% 8/51 • Within 30 days of study treatment, an average of 1 year
Vascular disorders Phlebitis	15.7% 8/51 • Within 30 days of study treatment, an average of 1 year
Skin and subcutaneous tissue disorders Rash maculo-papular	15.7% 8/51 • Within 30 days of study treatment, an average of 1 year
Investigations Weight loss	15.7% 8/51 • Within 30 days of study treatment, an average of 1 year
Investigations Aspartate aminotransferase increased	13.7% 7/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Gastroesophageal reflux disease	13.7% 7/51 • Within 30 days of study treatment, an average of 1 year
Investigations Lymphocyte count decreased	13.7% 7/51 • Within 30 days of study treatment, an average of 1 year
Renal and urinary disorders Cystitis noninfective	11.8% 6/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hypokalemia	11.8% 6/51 • Within 30 days of study treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Cough	9.8% 5/51 • Within 30 days of study treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Hiccups	9.8% 5/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hyponatremia	9.8% 5/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Anorexia	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Musculoskeletal and connective tissue disorders Back pain	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Investigations Blood bilirubin increased	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Eye disorders Blurred vision	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Dyspepsia	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Gastrointestinal disorders Flatulence	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Metabolism and nutrition disorders Hyperkalemia	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Vascular disorders Hypertension	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Investigations INR increased	7.8% 4/51 • Within 30 days of study treatment, an average of 1 year
Psychiatric disorders Anxiety	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year
Nervous system disorders Dizziness	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year
Musculoskeletal and connective tissue disorders Generalized muscle weakness	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year
Psychiatric disorders Insomnia	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year
Respiratory, thoracic and mediastinal disorders Sore throat	5.9% 3/51 • Within 30 days of study treatment, an average of 1 year

Additional Information

Dean Bajorin, MD

Memorial Sloan Kettering Cancer Center

Phone: 646-888-4700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place