Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma

Phase 2

Completed

Interventions: Drug: Methotrexate
Drug: Doxorubicin
Drug: vinblastine
Drug: cisplatin
Drug: Pegfilgrastim

Brief Summary: The purpose of this research study is to test the effectiveness of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in combination with pegfilgrastim followed by radical surgery in patients with muscle-invasive urothelial carcinoma.

Detailed Description: * Participants will be given a study infusion schedule for each treatment cycle. Each treatment cycle lasts three weeks. The infusion of methotrexate will take place on the first day of each cycle. Infusions of vinblastine, doxorubicin and cisplatin will take place on the second day and an injection of pegfilgrastim will be given on the third day.

* During all treatment cycles participants will have a physical exam and will be asked questions about their general health and any problems they might be having and any medications they may be taking.

* Following completion of study treatment, but before surgery, participants will have an assessment of their tumor by CT scan of the chest and and MRI of the abdomen and pelvis.

* Following the participants surgery, we would like to keep track of their medical condition indefinitely, or until this study is officially completed. We would like to do this by calling the participants on the telephone once a year to see how they are doing.

Recruitment & Eligibility

Inclusion Criteria

Histologic proof of urothelial cancer. Patients with all histologic subtypes are eligible as long as transitional cell carcinoma is predominant, with the exception of more than a few clusters of small cell carcinoma, which is treated with different chemotherapy and thus are ineligible
Patients with primary tumors arising in the bladder or urethra are eligible if they have clinical T2-T4a disease
Patients with primary tumors arising in the ureter or renal pelvis are eligible if they have either grade 3 tumors, or radiographic abnormality large enough to be recognized as an abnormal mass by CT/imaging
Evaluation by a urologist and be deemed to be acceptable surgical candidates within 3 months of registration
Adequate physiologic reserves as outlined in the protocol
Clinical or pathologic N1 lymph node involvement (involvement of a single lymph node < 2cm in greatest dimension) are eligible. Patients with N2-3 or M1 disease are ineligible
Determination of LV function with an EF > 50%
Women of child-bearing potential must have a negative pregnancy test
Patients of child-bearing or father-bearing potential must agree to use an acceptable form of birth control while on the study
Patients with prior malignancy are eligible provided that the expected outcome from the prior cancer is such that this will not interfere in the delivery of this therapy, or the assessment of response in the cystectomy specimen
18 years of age or older

Exclusion Criteria

Current, recent (within 3 weeks), or planned participation with other experimental anti-cancer medications as part of clinical trials
Prior treatment with doxorubicin
Prior systemic cytoreductive chemotherapy for bladder cancer
Blood pressure of > 160/100 mmHg. Patients whose blood pressure can be controlled with oral medication are eligible
NYHA Grade II or greater congestive heart failure
History of myocardial infarction or unstable angina within 6 months prior to study enrollment
History of stroke or transient ischemic attack within 6 months prior to study enrollment
Clinically significant peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Known history of central nervous system or brain metastases
Major surgical procedure, significant traumatic injury within 21 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
Lactating women
Patients who are not candidates for surgery, or unwilling to undergo surgery
Patients with significant fluid collection
Known hypersensitivity to any component of cisplatin, methotrexate, vinblastine, doxorubicin or pegfilgrastim

Arm && Interventions

Group	Intervention	Description
Dose Dense MVAC	Pegfilgrastim	Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin
Dose Dense MVAC	Methotrexate	Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin
Dose Dense MVAC	Doxorubicin	Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin
Dose Dense MVAC	vinblastine	Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin
Dose Dense MVAC	cisplatin	Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin

Primary Outcome Measures

Name	Time	Method
Number of Patients Achieving Pathologic Response	After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)	Pathological response is defined as down-staging to \</=pT1, N0 after chemotherapy with pegfilgrastim support.

Secondary Outcome Measures

Name	Time	Method
Number of Patients Experiencing Febrile Neutropenia	After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)	Febrile neutropenia defined per CTCAEv3 as Grade 3 or higher and treatment attribution possibly, probably or definitely-related.
Number of Patients Experiencing Surgery-related Toxicity	Surgery + 30 days	Surgery-related toxicity defined per CTCAEv3 as Grade 2 or higher and treatment attribution possibly, probably or definitely-related.

Locations (4): Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Lahey Clinic
🇺🇸
Burlington, Massachusetts, United States
University of Pittsburgh Cancer Institute
🇺🇸
Pittsburgh, Pennsylvania, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States