Bladder CancerPhase 2NCT00808639
Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma
A Phase 2 study testing Methotrexate, Doxorubicin and vinblastine in people with Bladder Cancer and Muscle-invasive Bladder Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Muscle-invasive Bladder Cancer
- What is being tested?
- Methotrexate, Doxorubicin and vinblastine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2008to Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Lahey Clinic
Burlington, Massachusetts, 01805
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase II Trial of Neoadjuvant Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma
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.
Read the 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.
- Conditions
- Bladder Cancer, Muscle-invasive Bladder Cancer
- Being tested
- Methotrexate, Doxorubicin, vinblastine, cisplatin, Pegfilgrastim
- Keywords
- pegfilgrastim, MVAC
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
intravenously 30mg/m2 over 30 minutes
DoxorubicinDrug
intravenously 30mg/ms over 15 minutes
vinblastineDrug
intravenously 3mg/m2 over 30 minutes
cisplatinDrug
intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion
PegfilgrastimDrug
Given subcutaneously 24 hours after last chemotherapy dose
| Study group | Role | What they receive |
|---|---|---|
| Dose Dense MVAC | Experimental | Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin Receives: Drug: Methotrexate; Drug: Doxorubicin; Drug: vinblastine; Drug: cisplatin; Drug: Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Achieving Pathologic Response
Pathological response is defined as down-staging to </=pT1, N0 after chemotherapy with pegfilgrastim support.
Measured: After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)
Secondary outcomes (2)
Number of Patients Experiencing Febrile Neutropenia
Febrile neutropenia defined per CTCAEv3 as Grade 3 or higher and treatment attribution possibly, probably or definitely-related.
Measured: After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)
Number of Patients Experiencing Surgery-related Toxicity
Surgery-related toxicity defined per CTCAEv3 as Grade 2 or higher and treatment attribution possibly, probably or definitely-related.
Measured: Surgery + 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2008 (estimated)
- Study startDec 2008
- Primary completionDec 2013
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Toni Choueiri, MD, Dana-Farber Cancer Institute
- Investigators
- Toni Choueiri, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00808639
- Sponsor's protocol ID
- 08-208
- Status last verified
- Sep 2016
- First submitted
- 15 Dec 2008
- Last updated
- 24 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, Bubley GJ, Stack EC, Signoretti S, Walsh M, Steele G, Hirsch M, Sweeney CJ, Taplin ME, Kibel AS, Krajewski KM, Kantoff PW, Ross RW, Rosenberg JE. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20;32(18):1889-94. doi: 10.1200/JCO.2013.52.4785. Epub 2014 May 12.
PubMed 24821883
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Neoadjuvant Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT00808639
- Acronym / sponsor ID
- 08-208
- Conditions
- Bladder Cancer, Muscle-invasive Bladder Cancer
- Keywords
- pegfilgrastim, MVAC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Amgen
- Study start
- Dec 2008
- Primary completion
- Dec 2013 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 16 Dec 2008 (estimated)
- Results
- Posted 15 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dose Dense MVAC | Experimental | Drug: Methotrexate, Drug: Doxorubicin, Drug: vinblastine, Drug: cisplatin, Drug: PegfilgrastimChemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methotrexateintravenously 30mg/m2 over 30 minutes | Drug | Dose Dense MVAC |
| Doxorubicinintravenously 30mg/ms over 15 minutes | Drug | Dose Dense MVAC |
| vinblastineintravenously 3mg/m2 over 30 minutes | Drug | Dose Dense MVAC |
| cisplatinintravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion | Drug | Dose Dense MVAC |
| PegfilgrastimGiven subcutaneously 24 hours after last chemotherapy dose | Drug | Dose Dense MVAC |
Primary outcome
Number of Patients Achieving Pathologic Response
Time frame: 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.
2 secondary outcomes
Number of Patients Experiencing Febrile Neutropenia
Time frame: After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)
Number of Patients Experiencing Surgery-related Toxicity
Time frame: Surgery + 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24821883Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, Bubley GJ, Stack EC, Signoretti S, Walsh M, Steele G, Hirsch M, Sweeney CJ, Taplin ME, Kibel AS, Krajewski KM, Kantoff PW, Ross RW, Rosenberg JE. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20;32(18):1889-94. doi: 10.1200/JCO.2013.52.4785. Epub 2014 May 12.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Toni Choueiri, MD principal investigator
Dana-Farber Cancer Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methotrexate, Doxorubicin and vinblastine in people with Bladder Cancer and Muscle-invasive Bladder Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Achieving Pathologic Response (time frame: After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00808639, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2016.