Evaluation of Oxaliplatin and Gemcitabine in Patients With Metastatic Bladder Cancer

• Sponsor: University of California, Irvine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT04039867
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arm: 1
• Actual Duration (Months): 80.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial evaluated the impact of Oxaliplatin and Gemcitabine in patients with recurrent or advanced transitional cell carcinoma of the bladder. The combination of Oxaliplatin and Gemcitabine is considered investigational and this study will help in determining if their activity and toxicity profiles are comparable or better than the standard regimens.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Transitional Cell	Drug: Oxaliplatin with Gemcitabine	Phase 2

Detailed Description

The combination of Oxaliplatin and Gemcitabine has synergistic effects on a variety of human cancer cell lines in vitro. Clinically, it has demonstrated activity in other malignancies including lung, and pancreas. In the former study, poor prognosis advanced non-small cell lung cancer patients received Gemcitabine 1000mg/m2 and Oxaliplatin 65mg/m2 both on days 1 and 8. The overall response rate was 16%, with no reports of neutropenic fever. In the latter study, locally advanced and metastatic pancreatic cancer patients received Gemcitabine 1000mg/m2 on day 1 and Oxaliplatin 100mg/m2 on day 2 every 2 weeks. The overall response rate was 31%. The toxicity profile included grades 3 to 4 neutropenia and thrombocytopenia in 11%, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths

There has been one feasibility study evaluating the combination of Oxaliplatin and Gemcitabine in advanced transitional cell carcinoma (TCC) of the urothelium. Twenty patients with advanced urothelial carcinomas who were treated with Gemcitabine and Oxaliplatin at 1500mg/m2 and 85mg/m2 IV respectively, both on day 1 of a 14 day cycle. The median number of cycles was 5 and ranged from 1 to 7. A total of 90 cycles were delivered with 87 assessable for toxicity in 19 patients. No neutropenic fever occurred and G-CSF was not used although allowed as needed. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 9 (10%) and 3 (3%) of the courses given respectively. Grades 1 to 2 neuropathy was noted to be common with only one patient suffering grade 3 neuropathy. Non-hematologic adverse effects were found to be mild. Response rates were not provided.

In summary, there is favorable evidence of antitumor activity in vitro and in clinical studies for a variety of cancers. Furthermore, the toxicity profile of this combination is also favorable. It is therefore logical to evaluate the effectiveness and tolerability of this combination in advanced urothelial carcinoma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Oxaliplatin and Gemcitabine in Patients With Metastatic Bladder Cancer
• Actual Study Start Date: Jan 20, 2005
• Actual Primary Completion Date: Oct 6, 2011
• Actual Study Completion Date: Oct 6, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxaliplatin with Gemcitabine Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.	Drug: Oxaliplatin with Gemcitabine; Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.; Other Names: Gemzar Eloxatin

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events to Evaluate Tolerability of Oxaliplatin With Gemcitabine [From date of registration until treatment completion, disease progression or other reasons for removal from protocol treatments, whichever came first, an average of 1 year.]

   To evaluate the tolerability of administering Oxaliplatin in combination with gemcitabine in patients with recurrent or advanced TCC bladder. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0.

Secondary Outcome Measures

1. Overall Response Rate as Assessed by RECIST Criteria of Patients Who Received Gemcitabine and Oxaliplatin [From date of registration until first date of disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.]

   To assess the overall response rate to the combination of gemcitabine and Oxaliplatin in patients with recurrent or advanced TCC bladder. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI. Complete Response (CR) is defined as disappearance of all target lestions. Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions. Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR). ORR = CR + PR

2. Overall Survival of Patients Who Received Gemcitabine and Oxaliplatin [From date of registration for 5 years or until death from any cause, whichever came first.]

   To evaluate overall survival in patients with advanced TCC bladder treated with this combination of gemcitabine and Oxaliplatin.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• All patients must have histologically or cytologically confirmed diagnosis of transitional cell carcinoma of the bladder.

• Patients must have metastatic or locally recurrent transitional cell carcinoma of the bladder. Patients with locoregional disease must be considered incurable by means of locoregional therapy.

• All sites of disease must be assessed and designated as measurable or non- measurable disease as documented by CT, MRI, X-ray physical exam or nuclear exam. All measurable disease must be assessed within 28 days prior to registration. All non-measurable disease must be assessed within 42 days prior to registration.

• Patients must not have more than one prior chemotherapy regimen for recurrent/metastatic disease. Patients with initial locally advanced but nonmetastatic disease are allowed to have one prior chemotherapy regimen as part of the primary curative therapy. All chemotherapy must be completed 4 weeks prior to registration. Any number of prior biologic therapies (e.g. chimeric antibodies or kinase inhibitors) is permitted as part of the chemotherapy regimen.

• Patients may have received prior radiotherapy if there has been complete recovery from all radiation-induced toxicities. At least 4 weeks must have elapsed from the completion of radiation therapy to the time of registration. If lesions within the radiation port are to be used to assess response to therapy, those lesions must have demonstrated clear progression by the criteria outlined in Section 10.1.2V following completion of radiation therapy.

• Patients must not have a surgical procedure for bladder cancer within 4 weeks prior to registration. Patients must have completely recovered from all surgery prior to registration.

• Patients must have adequate bone marrow reserve as evidenced by ANC > 1,500 μl and platelets > 100,000/ μl obtained within 14 days prior to registration.

• Patients must have adequate hepatic function as evidenced by serum bilirubin <1.5x the institutional upper limit of normal. Serum transaminase (SGOT or SGPT) be must < 1.5 x the institutional upper limit of normal serum unless the liver is involved with tumor, in which case serum transaminase (SGOT or SGPT) must be < 5 x the institutional limit of normal. These tests must be obtained within 14 days prior to registration.

• Patients must have a creatinine < 2 x the institutional upper limit of normal obtained within 14 days prior to registration.

• All patients must be 18 years of age or older.

• Patients must have a Zubrod performance of 0-2.

• Patients must not have prior therapy with Oxaliplatin or Gemcitabine.

Exclusion Criteria

• Patients with severe psychiatric disorder are not eligible.

• Patients with known brain metastasis are not eligible. However, brain imaging studies are not required for eligibility if the patient has no neurological signs or symptoms. If brain imaging studies are performed, they must be negative for disease.

• No other prior malignancy is allowed except for adequately treated basal cell or squamous cell carcinoma, in situ cervical cancer, or adequately treated Stage I and II cancer from which the patient is in complete remission, or any other malignancy from which the patient has been disease-free for 5 years.

• Patients with any evidence of active or uncontrolled infection, recent myocardial infarction, unstable angina, or life-threatening arrhythmia are not eligible.

• Patients with any evidence of active or uncontrolled infection, recent myocardial infarction, unstable angina, or life-threatening arrhythmia are not eligible.

• Patients with severe psychiatric disorder are not eligible.

• Patients with known brain metastasis are not eligible. However, brain imaging studies are not required for eligibility if the patient has no neurological signs or symptoms. If brain imaging studies are performed, they must be negative for disease.

• No other prior malignancy is allowed except for adequately treated basal cell or squamous cell carcinoma, in situ cervical cancer, or adequately treated Stage I and II cancer from which the patient is in complete remission, or any other malignancy from which the patient has been disease-free for 5 years.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chao Family Comprehensive Cancer Center, University of California, Irvine	Orange	California	United States	92868

Sponsors and Collaborators

• University of California, Irvine

Investigators

• Principal Investigator: John P Fruehauf, MD, PhD, University of California, Irvine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, Irvine
• ClinicalTrials.gov Identifier: NCT04039867
• Other Study ID Numbers: UCI 04-35 [HS# 2004-3920]; 2004-3920; NCI-2011-01249
• First Posted: Jul 31, 2019
• Last Update Posted: Apr 13, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of California, Irvine: Carcinoma, Transitional Cell; Bladder Cancer; oxaliplatin; Gemcitabine
• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Gemcitabine; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	Oxaliplatin With Gemcitabine
Arm/Group Description	Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin. Oxaliplatin with Gemcitabine: Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.
Period Title: Overall Study
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Oxaliplatin With Gemcitabine
Arm/Group Description	Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin. Oxaliplatin with Gemcitabine: Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.
Overall Participants	17
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	72
Sex: Female, Male (Count of Participants)
Female	7 41.2%
Male	10 58.8%
Region of Enrollment (participants) [Number]
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events to Evaluate Tolerability of Oxaliplatin With Gemcitabine
Description	To evaluate the tolerability of administering Oxaliplatin in combination with gemcitabine in patients with recurrent or advanced TCC bladder. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0.
Time Frame	From date of registration until treatment completion, disease progression or other reasons for removal from protocol treatments, whichever came first, an average of 1 year.

Outcome Measure Data

Analysis Population Description

Please refer to the Adverse Event tables for specifics.

Arm/Group Title	Oxaliplatin With Gemcitabine
Arm/Group Description	Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin. Oxaliplatin with Gemcitabine: Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.
Measure Participants	17
Count of Participants [Participants]	17 100%

2. Secondary Outcome

Title	Overall Response Rate as Assessed by RECIST Criteria of Patients Who Received Gemcitabine and Oxaliplatin
Description	To assess the overall response rate to the combination of gemcitabine and Oxaliplatin in patients with recurrent or advanced TCC bladder. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI. Complete Response (CR) is defined as disappearance of all target lestions. Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions. Overall response rate (ORR) is defined as confirmed complete response (CR) and partial response (PR). ORR = CR + PR
Time Frame	From date of registration until first date of disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

Outcome Measure Data

Analysis Population Description

Only 14 were accessable for response. One subject never started treatment, two dropped out of the study and one died prior to first assessment.

Arm/Group Title	Oxaliplatin With Gemcitabine
Arm/Group Description	Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin. Oxaliplatin with Gemcitabine: Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.
Measure Participants	14
Number [participants]	5 29.4%

3. Secondary Outcome

Title	Overall Survival of Patients Who Received Gemcitabine and Oxaliplatin
Description	To evaluate overall survival in patients with advanced TCC bladder treated with this combination of gemcitabine and Oxaliplatin.
Time Frame	From date of registration for 5 years or until death from any cause, whichever came first.

Outcome Measure Data

Analysis Population Description

All treated patients were included in this analysis.

Arm/Group Title	Oxaliplatin With Gemcitabine
Arm/Group Description	Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin. Oxaliplatin with Gemcitabine: Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.
Measure Participants	17
Median (95% Confidence Interval) [days]	314

Adverse Events

Time Frame	From date of registration until treatment completion, disease progression or other reasons for removal from protocol treatments, whichever came first, an average of 1 year.
Adverse Event Reporting Description	Toxicity was graded according to National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0. Safety was assessed through adverse event monitoring, physical examinations, vital signs and clinical laboratory tests before each dosing.
Arm/Group Title	Oxaliplatin With Gemcitabine
Arm/Group Description	Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin. Oxaliplatin with Gemcitabine: Oxaliplatin will be given as an intravenous infusion over 60 minutes on Days 1 and 14 at a dose of 100 mg/m2 for each cycle. Gemcitabine (1000 mg/m2) will be given on days 1 and 14 as an intravenous infusion over 30 minutes immediately prior to Oxaliplatin.
All Cause Mortality
	Oxaliplatin With Gemcitabine
	Affected / at Risk (%)	# Events
Total	10/17 (58.8%)
Serious Adverse Events
	Oxaliplatin With Gemcitabine
	Affected / at Risk (%)	# Events
Total	11/17 (64.7%)
Blood and lymphatic system disorders
Anemia	2/17 (11.8%)
Thrombocytopenia	6/17 (35.3%)
Neutropenia	2/17 (11.8%)
Lymphopenia	1/17 (5.9%)
General disorders
Fatigue	3/17 (17.6%)
Nervous system disorders
Sensory Neuropathy	2/17 (11.8%)
Other (Not Including Serious) Adverse Events
	Oxaliplatin With Gemcitabine
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anemia	6/17 (35.3%)
Thrombocytopenia	1/17 (5.9%)
Gastrointestinal disorders
Diarrhea	3/17 (17.6%)
Constipation	6/17 (35.3%)
General disorders
Swelling	6/17 (35.3%)
Fatigue	9/17 (52.9%)
Nausea/vomiting	10/17 (58.8%)
Injection Site Reaction	4/17 (23.5%)
Chills	3/17 (17.6%)
Nervous system disorders
Cold sensitivity	4/17 (23.5%)
Sensory Neuropathy	5/17 (29.4%)
Psychiatric disorders
Anorexia	6/17 (35.3%)

Limitations/Caveats

The main limitation for our study was the small sample size.

More Information

Certain Agreements

All Principal Investigators ARE 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.