Dose Dense MVAC for Muscle Invasive Bladder Cancer

• Sponsor: Fox Chase Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01031420
• Collaborator: (none)
• Enrollment: 54
• Locations: 2
• Arm: 1
• Actual Duration (Months): 44
• Patients Per Site: 27
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Standard treatment for early stage bladder cancer is chemotherapy with methotrexate (M), vinblastine (V), adriamycin (A), and cisplatin (C) followed by surgical removal of any remaining cancer and the bladder with the intent of cure. The M V chemotherapy is usually given every 14 days with the AC given along each 28 days. This study looks at giving the same drugs at the same doses closer together, all drugs every 14 days, with the support of growth factor medication to promote growth of the white blood cells and platelets and allow chemotherapy to be finished sooner and surgery to be done sooner.

Condition or Disease	Intervention/Treatment	Phase
Muscle Invasive Bladder Cancer; High Risk Urothelial Carcinoma of the Upper Urinary Tracts	Drug: single arm dose dense MVAC	Phase 2

Detailed Description

Primary Objective To assess the rate of complete response (pT0) at cystectomy or ureterectomy following preoperative dose dense MVAC (DD-MVAC) in patients with muscle invasive urothelial carcinoma of the bladder or high grade upper tract urothelial carcinoma.

Secondary Objectives To assess the toxicity profile of DD-MVAC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to compare incidence of toxicity to the historical standard described by Grossman et al. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD-MVAC. To compare complete response rates between the following subgroups of study patients: Among bladder patients: Clinical N0 versus N1 (Appendix B) Among bladder patients: T2 stage without high risk features versus T2 with high risk features plus those with > T2 stage.

Three 14 day cycles of:

Methotrexate 30 mg/m2 IV push or infusion over 2-3 minutes. Day 1

Vinblastine 3 mg/m2 Slow IV push or infusion over Day 1

Doxorubicin 30 mg/m2 Slow IV push or infusion over 15 minutes Day 1

Cisplatin 70 mg/m2 IV infusion over 4 hours Note: May divide dose over two sequential days (35 mg/m2/d x 2 days) if creatinine clearance 50-59 mL/min Day 1* (or divided over Day 1 and Day 2)

Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy.

Followed in 4-8 weeks by radical cystectomy/ureterectomy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Neoadjuvant Dose Dense MVAC in Muscle Invasive Bladder Cancer and High Risk Urothelial Carcinoma of the Upper Urinary Tract
• Actual Study Start Date: Dec 7, 2009
• Actual Primary Completion Date: Jul 19, 2013
• Actual Study Completion Date: Aug 7, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: dose dense MVAC standard doses of MVAC given every 14 days x 3.

Drug: single arm dose dense MVAC; standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.; Other Names: methotrexate (MTX) sodium MTX Mexate Mexate-AQ Foex Folex Abitrexate Rheumatrex amethopterin Velban Velsar AlkabanAQ Velbe vinblastine sulfate vincaleukoblastine VLB doxorubicin doxorubicin hydrochloride liposomal Doxil, Rubex Adria cis-platinum, cisdiammineddichloroplatinum, CDDP Platinol platinum

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC [Following completion of the 3rd/final cycle of chemotherapy (about week 9) by CT imaging and at time of surgery for pathologic response.]

   complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.

Secondary Outcome Measures

1. Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting. [Ongoing throughout treatment at each MD visit every 14 days.]

   Defined by number of patients who complete all three cycles of treatment without dose reduction

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• histologically confirmed urothelial carcinoma of bladder, ureter, or renal pelvis. T2-T4 and muscle invasion must be established by TURBT. Upper tract must be high grade. N0-N1 are eligible.

• candidate for radical cystectomy, nephroureterectomy, or segmental ureterectomy with goal of cure.

->/= 18 years old

• ECOG performance status 0-1.

• Adequate marrow and organ function.

• May enter on therapeutic anticoagulation if it can be safely held during perioperative period.

• No women of childbearing potential, pregnant or breastfeeding.

• LVEF >/= 50 %

• Patients with history of other non-urothelial malignancies may enroll if: 1)no evidence of distant disease w/in last year. 2)No anticancer treatment for >/= 1 year other than adjuvant treatment or treatment for secondary prevention. 3) Less than 360 mg/m2 lifetime dose of adriamycin.

• ability to understand and willingness to sign written informed consent and HIPAA.

Exclusion Criteria:

• Intravesicular therapy w/in 4 weeks of study entry or those who have not recovered from adverse effects of such agents administered more than 4 weeks earlier.

• Patients may not be receiving any investigational agents within 4 weeks of study entry.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Methotrexate, Vinblastine, Adriamycin or Cisplatin or other agents used in the study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects of cytotoxic chemotherapy.

• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

-. Patients who have undergone prior pelvic radiation are excluded due to risk of life threatening myelosuppression.

• Patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma or cytotoxic chemotherapy for another malignancy within 1 year of study entry are ineligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
2	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111

Sponsors and Collaborators

• Fox Chase Cancer Center

Investigators

• Principal Investigator: Elizabeth Plimack, MD, Fox Chase Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Pubmed.gov

Publications

None provided.

• Responsible Party: Fox Chase Cancer Center
• ClinicalTrials.gov Identifier: NCT01031420
• Other Study ID Numbers: FER-GU-026; NCI-2010-01910
• First Posted: Dec 14, 2009
• Last Update Posted: Sep 17, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Fox Chase Cancer Center: bladder; cancer; invasive
• Additional relevant MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Kidney Neoplasms; Ureteral Neoplasms; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vinblastine

Study Results

Participant Flow

Arm/Group Title	Dose Dense MVAC
Arm/Group Description	standard doses of MVAC given every 14 days x 3. single arm dose dense MVAC: standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Period Title: Overall Study
STARTED	54
COMPLETED	44
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Dose Dense MVAC
Arm/Group Description	standard doses of MVAC given every 14 days x 3. single arm dose dense MVAC: standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Overall Participants	54
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	26 48.1%
>=65 years	28 51.9%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Sex: Female, Male (Count of Participants)
Female	14 25.9%
Male	40 74.1%
Region of Enrollment (participants) [Number]
United States	54 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC
Description	complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.
Time Frame	Following completion of the 3rd/final cycle of chemotherapy (about week 9) by CT imaging and at time of surgery for pathologic response.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Dense MVAC
Arm/Group Description	standard doses of MVAC given every 14 days x 3. single arm dose dense MVAC: standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Measure Participants	44
Number (95% Confidence Interval) [percentage of total participants]	38 70.4%

2. Secondary Outcome

Title	Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting.
Description	Defined by number of patients who complete all three cycles of treatment without dose reduction
Time Frame	Ongoing throughout treatment at each MD visit every 14 days.

Outcome Measure Data

Analysis Population Description

Forty patients were evaluable for response as predefined in the protocol.

Arm/Group Title	Dose Dense MVAC
Arm/Group Description	standard doses of MVAC given every 14 days x 3. single arm dose dense MVAC: standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Measure Participants	40
All three cycles of chemotherapy were completed	37 68.5%
Discontinued chemotherapy	3 5.6%

Adverse Events

Arm/Group Title	Dose Dense MVAC
Arm/Group Description	standard doses of MVAC given every 14 days x 3. single arm dose dense MVAC: standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
All Cause Mortality
	Dose Dense MVAC
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Dose Dense MVAC
	Affected / at Risk (%)	# Events
Total	22/40 (55%)
Blood and lymphatic system disorders
Anemia	3/40 (7.5%)
Lymphocytopenia	3/40 (7.5%)
Neutropenia	2/40 (5%)
Thrombocytopenia	1/40 (2.5%)
Lymphopenia	1/40 (2.5%)
Gastrointestinal disorders
Mucositis	1/40 (2.5%)
General disorders
Fatigue	3/40 (7.5%)
Infections and infestations
Sepsis	1/40 (2.5%)
Pharyngitis	1/40 (2.5%)
Metabolism and nutrition disorders
Dehydration	1/40 (2.5%)
Anorexia	1/40 (2.5%)
Hyponatremia	1/40 (2.5%)
hypokalemia	1/40 (2.5%)
hyperkalemia	1/40 (2.5%)
Renal and urinary disorders
proteinuria	1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Dose Dense MVAC
	Affected / at Risk (%)	# Events
Total	0/40 (0%)

Limitations/Caveats

[Not Specified]

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.