Neoadjuvant Dose Dense MVAC in MIBC and Locally Advanced Urothelial Carcinoma

February 2, 2022 updated by: Kwonoh Park, MD phD, Pusan National University Yangsan Hospital

Efficacy and Safety of Neoadjuvant Chemotherapy With Dose Dense MVAC Followed by Radical Surgery in Patients With MIBC and Locally Advanced Urothelial Carcinoma of Bladder: Phase II, Single-arm Study

The objective is to investigate the efficacy and safety of four cycles of ddMVAC with G-CSF support in patients with MIBC and locally advanced UC

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

  • Currently, most treatment guidelines including NCCN recommend a neoadjuvant chemotherapy (NAC) as a standard of care in muscle invasive bladder cancer (MIBC).
  • Although standard NAC regimen is controversial due to rare of head to head study between each regimens, cisplatin based multidrug combination regimens such as MVAC, GP, and dose dense MVAC (ddMVAC) with G-CSF supports are regarded as a backbone treatment on the basis of the results from previous studies.
  • Application of NAC is still relatively slow adoption in real practice. These slow adoption result from intuitive concerns such as significant toxicity of multidrug combination chemotherapy represented by MVAC and delayed application of radical surgical treatment in non-responder
  • The ddMVAC with G-CSF support regimen showed an improved efficacy compared with GP regimen, and tolerable compared with standard MVAC using application of routine G-CSF support and high intensity of cisplatin.
  • In case of clinically lymph node evolvement (cN+) is not for strict NAC, but patient with cN+ UC have been treated induction chemotherapy of similar NAC regimens and surgical treatment. So, this study included MIBC plus cN+ UC as locally advanced UC.
  • In Korea, there is a low adoption of NAC, additionally rare of ddMVAC with G-CFS in locally advanced UC. It is supposed concerns related with toxicity of ddMVAC. Although the concern is likely not true considering the previous result of the Western, there has not been studied ddMVAC as NAC in Asian including Korean.
  • The objective of this trial is to assess the efficacy and safety of four cycles of ddMVAC with G-CSF support in patients with locally advanced UC.

Study Type

Interventional

Enrollment (Anticipated)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Korea, Republic of
    • Gyeongsangnam-do
      • Yangsan, Gyeongsangnam-do, Korea, Republic of, 50612
        • Recruiting
        • Pusan National University Yangsan Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with histologically or cytologically confirmed urothelial cancer of bladder.
  2. Locally advanced status for planning surgical treatment (Bladder, confirm muscle invasiveness using TURBT, or cT3-4a and N1-3 using imaging studies)
  3. Age 18 years or older
  4. Eastern Cooperative Oncology Group performance status 0-1

  5. Adequate organ and bone marrow function for cisplatin based chemotherapy

    A. Adequate bone marrow function: Absolute Neutrophil Count (ANC) ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9 g/dL)

    B. Adequate renal function: creatinine < 1.5 x upper normal limit (UNL) or creatinine clearance(Ccr) using Cockroft and Gault formula ≥ 50 ml/min

    C. Adequate hepatic function: bilirubin < 1.5 x UNL, AST/ALT levels <5.0 x UNL, alkaline phosphatase < 5 x UNL (except in case of bone metastasis without any liver disease)

  6. Women should use contraceptive medication for 6 months after the end of the study or she would be post-menopause status. Men should consent with the contraception for 6 months after the end of the study or he would be infertile.
  7. Patients should sign a written informed consent before study entry.

Exclusion Criteria:

  1. Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
  2. Excess of 4 weeks after initial imaging studies. But, allow the patients to enrollment of study if they is reassessed and reconfirm the localized status using subsequent imaging studies. In this case, clinical stage is decided as following imaging studies.
  3. Prior systemic chemotherapy (But prior intravesical chemotherapy was allowed)
  4. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
  5. History of treatment with drugs of another clinical trial within 30 days before enrollment.

  6. Concomitant severe medical, surgical, or psychiatric disease or problems which can affect the results of the clinical trial or have possibilities of unexpected medical problems caused be the drug of clinical trial

    A. Unstable angina, myocardial infarction, uncontrolled arrhythmias, symptomatic angina pectoris, cardiac failure within the previous 6 months

    B. Active infection which would compromise the patients

    C. Liver cirrohosis or chronic active hepatitis

    D. Poor pulmonary function (DLCO ≤ 50% of normal or resting O2 saturation ≤ 90%)

    E. Clinically significant hemoptysis or gastrointestinal bleeding within previous 6 months

    F. Major psychiatric disorders or other inadequate psychiatric problems according to the physicians decision

  7. History of another malignancy (but treated malignancy at least two years before enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid carcinoma are allowed even diagnosed less than 2 years before enrollment).
  8. Pregnant or lactating women, women of childbearing potential not employing adequate contraception

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ddMVAC
4 cycles of neoadjuvant chemotherapy using dose dense MVAC with G-CSF
Drug: dose dense MVAC with pegylated GCSF
Methotrexate, 30 mg/m2 IV bolus, Day 1 Vinblastine, 3 mg/m2 IV bolus, Day2 Doxorubicin, 30 mg/m2 IV bolus, Day2 Cisplatin, 70 mg/m2 IV over 1hr, Day2 Pegylated G-CSF, 6mg SC, Day 3 every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of pathologic response
Time Frame: From date of enrollment until curative intended surgical treatment, assess up to 2 years
No residual tumor (ypT0N0) and partial response (ypTis-1N0) in surgical specimen
From date of enrollment until curative intended surgical treatment, assess up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of pathologic complete response (pCR rate)
Time Frame: From date of enrollment until curative intended surgical treatment, assess up to 2 years
No residual tumor (ypT0N0) in surgical specimen
From date of enrollment until curative intended surgical treatment, assess up to 2 years
Overall survival (OS)
Time Frame: From date of enrollment until death, assess up to 3 years
Time from enrollment until death from any cause
From date of enrollment until death, assess up to 3 years
Event free survival (EFS)
Time Frame: From date of enrollment until death, assess up to 3 years
Time from enrollment until the earliest occurrence of disease progression in inoperablity, locoregional recurrence, distant metastasis, or death from any cause
From date of enrollment until death, assess up to 3 years
Adverse events related with ddMVAC
Time Frame: From date of enrollment until 8 weeks after last chemotherapy of ddMVAC
Adverse events related with ddMVAC using CTCAE 4.0
From date of enrollment until 8 weeks after last chemotherapy of ddMVAC
Surgical treatment related complication
Time Frame: From surgical treatment until 60 the days after surgical treatment
Surgical treatment related complication
From surgical treatment until 60 the days after surgical treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pusan National University Yangsan Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Actual)

January 31, 2022

Study Completion (Anticipated)

October 31, 2022

Study Registration Dates

First Submitted

August 5, 2019

First Submitted That Met QC Criteria

August 6, 2019

First Posted (Actual)

August 7, 2019

Study Record Updates

Last Update Posted (Actual)

February 18, 2022

Last Update Submitted That Met QC Criteria

February 2, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ddMVAC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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