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Bladder CancerPhase 2NCT00506155

Neoadjuvant Chemotherapy With Methotrexate, Vinblastine, Adriamycin and Cisplatin (M-VAC) Plus Avastin in Patients With Urothelial Cancer

A Phase 2 study testing Avastin, Cisplatin and Doxorubicin in people with Bladder Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The goal of this clinical research study is to learn how well bladder cancer responds to a combination treatment with Avastin and M-VAC (methotrexate, doxorubicin, vinblastine, and cisplatin) before surgery to remove the tumor. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Avastin, Cisplatin and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteUnited States
Study dates
Jun 2007to Aug 2014
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

  • Patients must have histologic proof of urothelial cancer. Patients with all histologic subtypes are eligible as long as transitional cell carcinoma predominant, with 2 exceptions:
  • More than a few clusters of small cell carcinoma are treated with different chemotherapy and are ineligible for this study
  • Patients with micropapillary tumor will be allowed irrespective of the extent of transitional cell carcinoma. A transitional cell component is not required in the setting of pure or extensive micropapillary tumors. Note that minor histologic components are acceptable.
  • Patients with primary tumors arising in the bladder or urethra are eligible if they demonstrate any of the following features:
  • A 3-dimensional mass on examination under anesthesia (EUA); ie: cT3b disease
  • Direct invasion of prostatic stroma or the vaginal wall: ie:cT4a disease
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  • Lymphovascular invasion on the specimen with >/= cT1 disease
  • Hydronephrosis present on CT scan or on renal ultrasound
  • Tumor involving bladder diverticulum.
  • Patients with more than a few areas of micropapillary histology are eligible, even if they do not meet the anatomic criteria for locally advanced disease enumerated above. Patients with micropapillary histology will be analyzed as a separate cohort.
  • Patients with primary tumors arising in the ureter or renal pelvis are eligible they have either grade 3 tumor, or a radiographic abnormality large enough to recognize as an abnormal mass by CT or MRI imaging. These patients may also be analyzed separately, since we do not have benchmark data for upper tract disease.
  • Patients must have an evaluation in the department of urology, and be deemed an acceptable surgical candidate.
  • Patients must have adequate physiologic reserves as by:
  • Zubrod performance status (PS) of </= 1; or 2 if of recent onset and due entirely to the cancer and not due to comorbidity (especially if the compromised performance status is related to uncontrolled pain which is expected to be rapidly reversible when therapy starts)
  • Normal WBC, ANC >/= 1,800, and platelet count >/= 150,000. Supranormal values judged to be of benign or inconsequential etiology are acceptable
  • Transaminase (AST or ALT) </= 3 * the ULN
  • Conjugated bilirubin </= 1.5 mg/dl (or total bilirubin </= 2.5 mg/dl)
  • Normal Serum Creatinine or Creatinine clearance (either measured or by Cockcroft-Gault formula) of >/= 50 ml/min.Cockcroft-Gault: CLcr = [(140-age) * wt(kg)]/[72 * Cr(mg/dL)] (For females, multiply by 0.85)
  • Patients (Pts) must NOT have clinical evidence of disease beyond the involved organ by either CT or MRI of the abdomen and pelvis, and chest X-ray. Pts with lymph node involvement are not eligible. In absence of a bone scan, pts should be free of bone pain and have an alk. phos. < 150% of the ULN, or a normal bone fraction of alk. phos. If these features are present, pts should have a bone scan and this should be interpreted as showing no evidence of metastatic disease to be eligible. In case of bladder tumors, cancer invading local organs (pT4a) but not pelvis sidewall (pT4b) are allowed.
  • Patients must have a determination of LV function with an EF >/= 50% to participate.
  • Women of child-bearing potential (i.e., who has had menses at any time in the preceding 24 consecutive months) must have a negative pregnancy test. Elevations of BHCG which are related to tumor (and not the rapid escalation associated with pregnancy, i.e. doubling time of 3-5 days) are acceptable.
  • Patients of child-bearing or child-fathering potential must agree to use an acceptable form of birth control while on the study, i.e. condoms.
  • Patients with second malignancies are eligible provided that the expected outcome from the second cancer is such that this will not interfere in the delivery of this therapy, or the assessment of response in the cystectomy specimen. The expected survival from the prior malignancy should reliably be > 4 years to be eligible for this study.
  • Patients must be >/= 18 years of age.

Who cannot join

  • Patients must not have current, recent (within 3 weeks), or planned participation with other experimental medication clinical trials.
  • Prior systemic cytoreductive chemotherapy for bladder cancer. Please note, that prior intra-vesical therapy is allowed.
  • Blood pressure of > 140/90 mmHg. Patients whose blood pressure is controlled with oral medication are eligible, as long as the blood pressure is </= 140/90 mmHg.
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • New York Heart Association (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 (e.g., aortic aneurysm, aortic dissection).
  • Symptomatic peripheral vascular disease.
  • Evidence of bleeding diathesis or coagulopathy.
  • Known history of central nervous system or brain metastases.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study. For the purpose of this study, Cystoscopy and ureteroscopy is not included as a major surgical procedure.
  • Lactating women.
  • Proteinuria at screening as demonstrated by either:
  • Urine protein:creatinine (UPC) ratio >/= 1.0 at screening OR
  • Urine dipstick for proteinuria > 2+ (or > 100 protein on urinalysis) Patients discovered to have >2+ proteinuria on dipstick urinalysis or >100 on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate <= 1g of protein in 24 hours to be eligible.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to therapy. Patients with Crohn's disease will be excluded.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, cavitation, or history of hemoptysis (bright red blood of 1/2 teaspoon or more; non-small cell lung cancer trials only).
  • Inability to comply with study and/or follow-up procedures, or sign informed consent.
  • Patients who are not candidates for surgery, or are unwilling to undergo surgery.
  • Patients with fluid collections (such as ascites, or pleural effusions) are not eligible for therapy as such collections may serve as a reservoir for methotrexate.
  • Know hypersensitivity to any component of Avastin.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase II Clinical Trial of Neoadjuvant Chemotherapy With M-VAC Plus Avastin in Patients With Locally Advanced Urothelial Cancer

The goal of this clinical research study is to learn how well bladder cancer responds to a combination treatment with Avastin and M-VAC (methotrexate, doxorubicin, vinblastine, and cisplatin) before surgery to remove the tumor.

Primary Objective:

Read more

To estimate the response of patients with locally advanced urothelial cancer treated with neoadjuvant chemotherapy with a combination of Dose Dense Methotrexate, Vinblastine, Adriamycin, and Cisplatin (DD-M-VAC) plus Avastin followed by radical surgery with curative intent. In this context, response will be defined as the absence of residual muscle invasive cancer in the resected specimen (<= pT1, N0.)

Secondary Objective:

To estimate the 4-year disease-free survival of patients with locally advanced urothelial cancer treated with neoadjuvant chemotherapy with DD-M-VAC plus Avastin followed by radical surgery with curative intent.

Document perioperative morbidity and mortality in this cohort, with reference to well-established historical standards.

Determine the effects of VEGF inhibition on angiogenesis and angiogenesis-related gene expression utilizing fluorescent tissue staining techniques that we have developed in the laboratory (such as two-color TUNEL, phospho-receptor, and microvessel density).

Interrogate downstream receptor signaling pathways to provide insight into the development of chemotherapy resistance, and hence hypothesis for its prevention.

Read the detailed description

Avastin is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels. Methotrexate, vinblastine, and doxorubicin are designed to disrupt the growth of cancer cells, which causes cancer cells to start to die. Cisplatin has an atom at its center that contains platinum. The platinum is designed to poison the cancer cells, which may cause them to eventually die.

If you are found to be eligible to take part in this study, you will be treated with the combination of Avastin, methotrexate, vinblastine, doxorubicin, and cisplatin. The study drugs and saline will be given through a needle in your vein. Avastin will be given over 90 minutes. Methotrexate will be given over 30 minutes. Vinblastine will be given over 30 minutes. Doxorubicin will be given over 15 minutes. Cisplatin will be given over 4 hours. You will also receive saline for hydration after you have completed the infusion of cisplatin. This will take up to 20 hours. If you have a catheter in place, the chemotherapy drugs as well as the saline will be given through the catheter. You will receive the study drugs 1 time every 2 weeks. Every 2 weeks is called a study "cycle".

On Day 1 of each cycle, you will have a physical exam, including measurement of your vital signs, height, and weight. You will be asked about any side effects you have experienced since your last visit. Blood (about 2 teaspoons) and urine will be collected for routine tests.

After 3 cycles of therapy, you will have a bone scan if your screening test showed signs of bone disease. You will also have a repeat cystoscopy. These tests will be done to check the status of the disease.

You will receive a total of 4 cycles of chemotherapy. At least 6 weeks after the last dose of Avastin, you will have a cystectomy (removal of your tumor). Your doctor will explain this procedure to you in detail. You will sign a separate consent form for this procedure.

After surgery, if you do not have disease in your lymph nodes or other sites, you will be taken off-study.

After surgery, if you still have disease in your lymph nodes or other sites, you will be eligible to continue treatment with Avastin. Therapy can be restarted no sooner than 28 days after your surgery. You will receive Avastin every 2 or 3 weeks through a needle in your vein. Every 2 or 3 weeks will be considered a study cycle.

Before each cycle of treatment, blood (about 1 teaspoon) will be drawn for routine tests. Urine will be collected every cycle for routine testing. Every 3 months you will have a CT scan or MRI to check the status of the disease.

You may continue to receive the study drug for up to 18 months of therapy. You will be taken off study in the disease gets worse or intolerable side effects occur.

Once you are off-study, you will have long term follow-up visits every 3-6 months for the first 30 months and then every year after that. These visits will continue for up to 4 years, or longer if your doctor thinks it is necessary. At these visits, you will have a CT or MRI scan of your abdomen and pelvis and a chest x-ray. Blood (about 1 teaspoons) will be drawn for routine testing.

This is an investigational study. Avastin is not FDA approved or commercially available for this indication. Its use in this study is considered to be investigational. Methotrexate, doxorubicin, vinblastine, and cisplatin are all FDA approved and commercially available. Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Bladder Cancer
Being tested
Avastin, Cisplatin, Doxorubicin, Methotrexate, Vinblastine Sulfate
Keywords
Bladder Cancer, Urothelial Cancer, Avastin, Bevacizumab, Cisplatin, Doxorubicin, Methotrexate, Vinblastine, M-VAC
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.

  • AvastinDrug

    Also called Bevacizumab, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

    10 mg/kg by vein over 90 minutes

  • CisplatinDrug

    Also called Platinol-AQ, Platinol, CDDP

    70 mg/m^2 by vein over 4 hours

  • DoxorubicinDrug

    Also called Adriamycin, Rubex

    30 mg/m^2 by vein over 15 minutes

  • MethotrexateDrug

    30 mg/m^2 by vein over 30 minutes

  • Vinblastine SulfateDrug

    3 mg/m^2 by vein over 30 minutes

Study groups in NCT00506155
Study groupRoleWhat they receive
Neoadjuvant Chemotherapy with M-VAC + AvastinExperimentalAvastin 10 mg/kg by vein over 90 minutes. Cisplatin 70 mg/m^2 by vein over 4 hours. Doxorubicin 30 mg/m^2 by vein over 15 minutes. Methotrexate 30 mg/m^2 by vein over 30 minutes. Vinblastine Sulfate 3 mg/m^2 by vein over 30 minutes.
Receives: Drug: Avastin; Drug: Cisplatin; Drug: Doxorubicin; Drug: Methotrexate; Drug: Vinblastine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen

    Number of participants out of total with a response defined as "downstaging" to <= pT1N0 in the resected specimen. A binary variable was defined for downstaging (pathologic stage below initial clinical stage and below pT1N1N0M0); staging using American Joint Committee on Cancer (AJCC) TNM system of "TNM"; T describes size tumor \& cancer spread into nearby tissue; N describes spread to nearby lymph nodes; \& M describes metastasis (spread to other parts of body). Numbers after T (such as T1, T2, T3, and T4) describe tumor size and/or amount of spread into nearby structures, higher the T number, the larger the tumor and/or more it has grown into nearby tissues. Responses of lesser magnitude scored as treatment failure. Response Evaluation Criteria In Solid Tumors (RECIST) criteria do not apply for this cohort of neoadjuvant participants since this study does not require measurable disease by traditional assessment.

    Measured: Following 20 weeks of chemotherapy

Secondary outcomes (1)

  1. 5-year Overall Survival (OS)

    The overall survival rate stated as a five-year survival rate, which is the percentage of participants in study who are alive five years after the start of treatment.

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionAug 2014
  4. Study completionAug 2014

Resources

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
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00506155
Sponsor's protocol ID
2006-0620
Status last verified
Mar 2016
First submitted
23 Jul 2007
Last updated
31 Mar 2016
Data monitoring committee
No

Publications

  • McConkey DJ, Choi W, Shen Y, Lee IL, Porten S, Matin SF, Kamat AM, Corn P, Millikan RE, Dinney C, Czerniak B, Siefker-Radtke AO. A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naive Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer. Eur Urol. 2016 May;69(5):855-62. doi: 10.1016/j.eururo.2015.08.034. Epub 2015 Sep 3.

    PubMed 26343003

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avastin, Cisplatin and Doxorubicin in people with Bladder Cancer, run by M.D. Anderson Cancer Center at 1 site 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 24 inclusion and 23 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 31 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 31 Mar 2016). 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 Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen (time frame: Following 20 weeks of chemotherapy). 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 NCT00506155, 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 31 Mar 2016.

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