Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy for TCC

• Sponsor: Noah Hahn, M.D. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00859339
• Collaborator: Pfizer (Industry), Hoosier Cancer Research Network (Other)
• Enrollment: 9
• Locations: 5
• Arm: 1
• Duration (Months): 25
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This trial will investigate the activity of sunitinib combined with cisplatin and gemcitabine followed by radical cystectomy in patients with Transitional Cell Carcinoma (TCC) of the Bladder.

Condition or Disease	Intervention/Treatment	Phase
Transitional Cell Carcinoma of the Bladder	Drug: Gemcitabine; Drug: Cisplatin; Drug: Sunitinib Malate; Procedure: Radical Cystectomy	Phase 2

Detailed Description

OUTLINE: This is a multi-center study.

• Gemcitabine ( 1000 mg/m2) IV days 1 and 8

• Cisplatin (70 mg/m2) IV day 1 and

• Sunitinib malate (37.5 mg) oral daily for days 1-14

The treatment regimen will be administered in four, 21-day, cycles followed by radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.

ECOG performance status 0 or 1

Hematopoietic:

• Absolute Neutrophil Count (ANC) > 1.5 K/mm3 [(IS): 1.5 x 109/L]

• Platelets > 100 K/mm3 [(IS): 100 x 109/L]

• Hemoglobin (Hgb) > 9.0 g/dL [(IS): 90 g/L]

Hepatic:

• Total bilirubin < 1.5 x Upper Limit of Normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 x ULN

• Alanine aminotransferase (ALT) ≤ 2.5 x ULN

Renal:

• Calculated creatinine clearance of > 60 cc/min

Cardiovascular:

• No uncontrolled angina, congestive heart failure or myocardial infarction or coronary/peripheral artery bypass graft within 6 months prior to registration for protocol therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Neoadjuvant Cisplatin, Gemcitabine and Sunitinib Malate Followed by Radical Cystectomy for Transitional Cell Carcinoma (TCC) of the Bladder: Hoosier Oncology Group GU07-123
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Treatment Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy	Drug: Gemcitabine; Gemcitabine ( 1000 mg/m2) IV days 1 and 8; Drug: Cisplatin; Cisplatin (70 mg/m2) IV day 1; Drug: Sunitinib Malate; Sunitinib malate (37.5 mg) oral daily for days 1-14; Procedure: Radical Cystectomy; Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.

Outcome Measures

Primary Outcome Measures

1. Pathological Complete Response (pCR) Rate. [18 months]

   number of participants with a pCR

Secondary Outcome Measures

1. Safety Profile [18 months]

   Evaluate the safety profile of Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy in participants with TCC

2. Objective Response Rate [18 months]

   To determine the objective response rate for patients with measurable disease according to RECIST.

3. Progression Free Survival [18 months]

4. Correlate Biomarker Expression [18 months]

   To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III) with no evidence of metastatic disease (focal squamous and/or adenocarcinoma differentiation allowed, sarcomatoid and small-cell components not allowed). Patient with any degree of fixation of the pelvic sidewall are not eligible.

• Must be willing to undergo a cystoscopy if tumor block is not available prior to registration for protocol therapy.

• Eligible for radical cystectomy as per the attending urologist.

• Prior radiation therapy to bone marrow is allowed to < 25% of the marrow, and must be completed at least 6 months prior to registration for protocol therapy

• Written informed consent and HIPAA authorization for release of personal health information.

• Age > 18 years at the time of consent.

• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.

• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy.

Exclusion Criteria:

• No prior radiotherapy to the pelvis.

• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason< grade 7 prostate cancers, or other cancer for which the patient has been disease-free for at least 5 years.

• No treatment with any investigational agent within 30 days prior to registration for protocol therapy.

• No cerebrovascular accident or transient ischemic attack within 6 months prior to registration for protocol therapy.

• No evidence of pulmonary embolism within 6 months prior to registration for protocol therapy.

• No uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy).

• No evidence of ongoing cardiac dysrhythmias of NCI CTCAE Version 3.0 grade 2.

• No history of uncontrolled/untreated thyroid dysfunction.

• No prolonged QTc interval (> 450 msec) on pre-entry electrocardiogram obtained within 28 days prior to being registered on study.

• Patients on warfarin (>2mg) for thrombosis must be able and willing to switch to low molecular weight heparin prior to registration for protocol therapy.

• No use of drugs having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide) within 7 days prior to registration for protocol therapy.

• No use of CYP3A4 inhibitors (see section 5.3 for a list) within 7 days of registration for protocol therapy.

• No use of CYP3A4 inducers (see section 5.3 for a list) within 14 days of registration for protocol therapy.

• No use of amiodarone (CYP3A4 inhibitor) within 6 months of registration for protocol therapy.

• Females must not be breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Florida	Gainesville	Florida	United States	32610
2	Indiana University Simon Cancer Center	Indianapolis	Indiana	United States	46202
3	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
4	Baylor College of Medicine	Houston	Texas	United States	77030
5	St. Bartholomew's Hospital (Barts)	London		United Kingdom	EC1A 7BE

Sponsors and Collaborators

• Noah Hahn, M.D.
• Pfizer
• Hoosier Cancer Research Network

Investigators

• Study Chair: Noah Hahn, M.D., Hoosier Cancer Research Network

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Hoosier Oncology Group Homepage

Publications

None provided.

• Responsible Party: Noah Hahn, M.D., Sponsor-Investigator, Hoosier Cancer Research Network
• ClinicalTrials.gov Identifier: NCT00859339
• Other Study ID Numbers: HOG GU07-123
• First Posted: Mar 11, 2009
• Last Update Posted: Apr 14, 2016
• Last Verified: Mar 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Noah Hahn, M.D., Sponsor-Investigator, Hoosier Cancer Research Network: TCC
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Gemcitabine; Sunitinib

Study Results

Participant Flow

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Overall Participants	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70
Sex: Female, Male (Count of Participants)
Female	1 11.1%
Male	8 88.9%
Region of Enrollment (participants) [Number]
United States	7 77.8%
United Kingdom	2 22.2%

Outcome Measures

1. Primary Outcome

Title	Pathological Complete Response (pCR) Rate.
Description	number of participants with a pCR
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

8 participants were evaluable for pCR

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Measure Participants	8
Number [particpants with pCR]	2

2. Secondary Outcome

Title	Safety Profile
Description	Evaluate the safety profile of Neoadjuvant Cisplatin, Gemcitabine, Sunitinib Malate + Radical Cystectomy in participants with TCC
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Measure Participants	9
Perioperative bleeding	4 44.4%
neutropenia	2 22.2%
neutropenic fever	1 11.1%
thrombocytopenia	1 11.1%
anemia	1 11.1%
nausea/emesis	3 33.3%
syncope	2 22.2%
myocardial infarction	1 11.1%
fatigue	1 11.1%

3. Secondary Outcome

Title	Objective Response Rate
Description	To determine the objective response rate for patients with measurable disease according to RECIST.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

No data was collected or analyzed for the secondary objective due to termination of the trial (toxicity)

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Measure Participants	0

4. Secondary Outcome

Title	Progression Free Survival
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

No data was collected or analyzed for the secondary objective due to termination of the trial (toxicity)

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Measure Participants	0

5. Secondary Outcome

Title	Correlate Biomarker Expression
Description	To evaluate the impact of sunitinib malate in combination with cisplatin and gemcitabine on expression of selected biomarkers.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

No data was collected or analyzed for the secondary objective due to termination of the trial (toxicity)

Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
Measure Participants	0

Adverse Events

Time Frame	From on-study to off-study, a maximum of four cycles plus time for recovery and radical cystectomy, a maximum of six months.
Arm/Group Title	CGS + Radical Cystectomy
Arm/Group Description	Neoadjuvant cisplatin, gemcitabine and sunitinib malate followed by radical cystectomy Gemcitabine: Gemcitabine ( 1000 mg/m2) IV days 1 and 8 Cisplatin: Cisplatin (70 mg/m2) IV day 1 Sunitinib Malate: Sunitinib malate (37.5 mg) oral daily for days 1-14 Radical Cystectomy: Radical cystectomy performed no sooner than 2 weeks but within 6 weeks of the last dose of sunitinib malate.
All Cause Mortality
	CGS + Radical Cystectomy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CGS + Radical Cystectomy
	Affected / at Risk (%)	# Events
Total	7/9 (77.8%)
Cardiac disorders
CARDIAC ISCHEMIA/INFARCTION	1/9 (11.1%)	1
Gastrointestinal disorders
HEMORRHAGE, GU / BLADDER	1/9 (11.1%)	1
NAUSEA	1/9 (11.1%)	1
ULCER, GI / ESOPHAGUS	1/9 (11.1%)	1
VOMITING	1/9 (11.1%)	1
Infections and infestations
INFECTION WITH GRADE 3 OR 4 NEUTROPHILS (ANC <1.0 X 10E9/L) / KIDNEY	1/9 (11.1%)	1
INFECTION - OTHER	1/9 (11.1%)	1
INFECTION WITH UNKNOWN ANC / WOUND	1/9 (11.1%)	1
Nervous system disorders
SYNCOPE (FAINTING)	1/9 (11.1%)	1
Renal and urinary disorders
OBSTRUCTION, GU / BLADDER	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	CGS + Radical Cystectomy
	Affected / at Risk (%)	# Events
Total	6/9 (66.7%)
Blood and lymphatic system disorders
EDEMA: LIMB	3/9 (33.3%)	3
HEMOGLOBIN	5/9 (55.6%)	13
LEUKOCYTES (TOTAL WBC)	3/9 (33.3%)	8
LYMPHOPENIA	1/9 (11.1%)	5
NEUTROPHILS/GRANULOCYTES (ANC/AGC)	5/9 (55.6%)	11
PLATELETS	3/9 (33.3%)	6
Cardiac disorders
HYPERTENSION	2/9 (22.2%)	2
HYPOTENSION	1/9 (11.1%)	1
PAIN / CARDIAC/HEART	1/9 (11.1%)	1
Endocrine disorders
THYROID FUNCTION, LOW (HYPOTHYROIDISM)	1/9 (11.1%)	2
Eye disorders
MUSCLE WEAKNESS, GENERALIZED OR SPECIFIC AREA (NOT DUE TO NEUROPATHY) / EXTRAOCULAR	1/9 (11.1%)	1
Gastrointestinal disorders
ANOREXIA	2/9 (22.2%)	2
CONSTIPATION	2/9 (22.2%)	4
DEHYDRATION	2/9 (22.2%)	2
DIARRHEA	3/9 (33.3%)	3
HEARTBURN/DYSPEPSIA	1/9 (11.1%)	2
HEMORRHAGE, GU / BLADDER	1/9 (11.1%)	1
NAUSEA	3/9 (33.3%)	3
PAIN / ABDOMEN NOS	2/9 (22.2%)	2
TASTE ALTERATION (DYSGEUSIA)	2/9 (22.2%)	3
VOMITING	2/9 (22.2%)	3
General disorders
FATIGUE (ASTHENIA, LETHARGY, MALAISE)	6/9 (66.7%)	10
INSOMNIA	3/9 (33.3%)	3
PAIN / BUTTOCK	1/9 (11.1%)	1
PAIN / HEAD/HEADACHE	1/9 (11.1%)	1
PAIN - OTHER	1/9 (11.1%)	2
WEIGHT LOSS	1/9 (11.1%)	1
Infections and infestations
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS / BLADDER (URINARY)	1/9 (11.1%)	1
INFECTION WITH UNKNOWN ANC / URINARY TRACT NOS	1/9 (11.1%)	1
Injury, poisoning and procedural complications
HEMORRHAGE/BLEEDING ASSOCIATED WITH SURGERY, INTRA-OPERATIVE OR POSTOPERATIVE	4/9 (44.4%)	4
Investigations
CALCIUM, SERUM-LOW (HYPOCALCEMIA)	2/9 (22.2%)	2
CREATININE	4/9 (44.4%)	6
GLUCOSE, SERUM-HIGH (HYPERGLYCEMIA)	1/9 (11.1%)	2
POTASSIUM, SERUM-LOW (HYPOKALEMIA)	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
PAIN / JOINT	1/9 (11.1%)	1
PAIN / MUSCLE	2/9 (22.2%)	2
Nervous system disorders
NEUROPATHY: SENSORY	1/9 (11.1%)	1
SYNCOPE (FAINTING)	1/9 (11.1%)	1
Psychiatric disorders
MOOD ALTERATION / DEPRESSION	1/9 (11.1%)	1
Renal and urinary disorders
BLADDER SPASMS	1/9 (11.1%)	1
OBSTRUCTION, GU / BLADDER	1/9 (11.1%)	1
PAIN / BLADDER	2/9 (22.2%)	2
URINE COLOR CHANGE	1/9 (11.1%)	2
Respiratory, thoracic and mediastinal disorders
DYSPNEA (SHORTNESS OF BREATH)	2/9 (22.2%)	3
PAIN / CHEST/THORAX NOS	1/9 (11.1%)	1
PULMONARY/UPPER RESPIRATORY - OTHER	1/9 (11.1%)	1
Skin and subcutaneous tissue disorders
HAIR LOSS/ALOPECIA (SCALP OR BODY)	2/9 (22.2%)	2

Limitations/Caveats

Study was terminated due to pre-defined stopping rules (patient toxicities)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.