Muscle Invasive Bladder CancerPhase 2NCT01031420
Dose Dense MVAC for Muscle Invasive Bladder Cancer
A Phase 2 study testing single arm dose dense MVAC in people with Muscle Invasive Bladder Cancer and High Risk Urothelial Carcinoma of the Upper Urinary Tracts, run by Fox Chase Cancer Center at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Muscle Invasive Bladder Cancer, High Risk Urothelial Carcinoma of the Upper Urinary Tracts
- What is being tested?
- single arm dose dense MVAC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 2 sitesUnited States
- Study dates
- 7 Dec 2009to 7 Aug 2013
- 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
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
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
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.
Read the 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.
- Conditions
- Muscle Invasive Bladder Cancer, High Risk Urothelial Carcinoma of the Upper Urinary Tracts
- Being tested
- single arm dose dense MVAC
- Keywords
- bladder, cancer, invasive
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
single arm dose dense MVACDrug
Also called methotrexate (MTX) sodium, MTX, Mexate, Mexate-AQ
standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| dose dense MVAC | Experimental | standard doses of MVAC given every 14 days x 3. Receives: Drug: single arm dose dense MVAC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC
complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.
Measured: Following completion of the 3rd/final cycle of chemotherapy (about week 9) by CT imaging and at time of surgery for pathologic response.
Secondary outcomes (1)
Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting.
Defined by number of patients who complete all three cycles of treatment without dose reduction
Measured: Ongoing throughout treatment at each MD visit every 14 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2009 (estimated)
- Study start7 Dec 2009
- Primary completion19 Jul 2013
- Study completion7 Aug 2013
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 Muscle Invasive Bladder CancerStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe 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
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elizabeth Plimack, MD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01031420
- Sponsor's protocol ID
- FER-GU-026
- Other IDs
- NCI-2010-01910
- Status last verified
- Aug 2019
- First submitted
- 3 Dec 2009
- Last updated
- 17 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, Chen DY, Lallas CD, Wong YN, Lin J, Kutikov A, Dotan E, Brennan TA, Palma N, Dulaimi E, Mehrazin R, Boorjian SA, Kelly WK, Uzzo RG, Hudes GR. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. doi: 10.1200/JCO.2013.53.2465. Epub 2014 May 12.
PubMed 24821881
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01031420
- Acronym / sponsor ID
- FER-GU-026
- Conditions
- Muscle Invasive Bladder Cancer, High Risk Urothelial Carcinoma of the Upper Urinary Tracts
- Keywords
- bladder, cancer, invasive
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 7 Dec 2009 (actual)
- Primary completion
- 19 Jul 2013 (actual)
- Study completion
- 7 Aug 2013 (actual)
- First posted
- 14 Dec 2009 (estimated)
- Results
- Posted 21 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- 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: single arm dose dense MVACstandard doses of MVAC given every 14 days x 3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
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 |
|---|---|---|
| single arm dose dense MVACAlso: methotrexate (MTX) sodium, MTX, Mexate, Mexate-AQstandard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days. | Drug | dose dense MVAC |
Primary outcome
Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC
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.
complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.
1 secondary outcome
Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting.
Time frame: Ongoing throughout treatment at each MD visit every 14 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24821881Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, Chen DY, Lallas CD, Wong YN, Lin J, Kutikov A, Dotan E, Brennan TA, Palma N, Dulaimi E, Mehrazin R, Boorjian SA, Kelly WK, Uzzo RG, Hudes GR. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. doi: 10.1200/JCO.2013.53.2465. Epub 2014 May 12.
- Pubmed.govLink provided by the sponsor.
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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.
Elizabeth Plimack, MD principal investigator
Fox Chase Cancer Center
2 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 single arm dose dense MVAC in people with Muscle Invasive Bladder Cancer and High Risk Urothelial Carcinoma of the Upper Urinary Tracts, run by Fox Chase Cancer Center at 2 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 10 inclusion and 8 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 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 21 Aug 2019). 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?
Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC (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.). 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 NCT01031420, 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 17 Sep 2019.