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Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02412670
Recruitment Status : Unknown
Verified July 2018 by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group ).
Recruitment status was:  Active, not recruiting
First Posted : April 9, 2015
Last Update Posted : July 29, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Tracking Information
First Submitted Date  ICMJE April 6, 2015
First Posted Date  ICMJE April 9, 2015
Last Update Posted Date July 29, 2019
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2015)
pCR rates [ Time Frame: Up to 5 years ]
Analyzed using a one-sided exact binomial test.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2015)
  • Recurrence-free survival [ Time Frame: From the date of surgery to disease recurrence or death from any cause, assessed up to 5 years ]
    Characterized using the method of Kaplan and Meier.
  • Event-free survival [ Time Frame: From registration to the earlier of recurrence, disease progression, new invasive primary cancer, or death from any cause, assessed up to 5 years ]
    Characterized using the method of Kaplan and Meier.
  • Bladder cancer-free survival [ Time Frame: From the date of surgery to the earlier of a return of bladder cancer or death from any cause, assessed up to 5 years ]
    Characterized using the method of Kaplan and Meier.
  • Cancer-specific survival [ Time Frame: From registration to death due to cancer, assessed up to 5 years ]
    Will be analyzed using Gray's method and cumulative incidence estimates will be reported.
  • The proportion of patients with renal insufficiency (CrCl < 60 ml/min) post chemotherapy and post nephroureterectomy [ Time Frame: Up to 60 days after completion of chemotherapy ]
    Will be reported along with exact binomial confidence intervals.
  • The proportion of patients with renal function improvement (CrCl < 60 ml/min at baseline and CrCl >= 60 ml/min on study) [ Time Frame: Up to 60 days after completion of chemotherapy ]
    Will be reported along with exact binomial confidence intervals.
  • Distribution of changes in renal function post chemotherapy and post surgery [ Time Frame: Baseline up to 60 days after completion of chemotherapy ]
  • Incidence of toxicities [ Time Frame: Up to 30 days from date of surgery ]
    The percent of patients with various toxicities will be tabulated.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer
Official Title  ICMJE A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma
Brief Summary This phase II trial studies how well giving chemotherapy before surgery works in treating patients with aggressive upper urinary tract cancer. Drugs used in chemotherapy, such as methotrexate, vinblastine, doxorubicin hydrochloride, cisplatin, gemcitabine hydrochloride, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Removing the affected upper urinary tract by surgery is the recommended treatment for upper urinary tract cancer, but can cause loss of kidney function and prevent patients from being able to receive chemotherapy after surgery. Giving chemotherapy before surgery, when the kidneys are working at their maximum, may allow less tissue to be removed during surgery and may be more effective in treating patients with high grade upper urinary tract cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the rate of complete pathologic response (pCR = pT0pN0) as assessed by standard pathologic review attained by neoadjuvant systemic chemotherapy and nephroureterectomy.

SECONDARY OBJECTIVES:

I. To evaluate the safety of neoadjuvant systemic chemotherapy in patients with upper tract urothelial carcinoma preceding nephroureterectomy.

II. To evaluate recurrence-free survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

III. To evaluate event-free survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

IV. To evaluate bladder cancer-free survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

V. To evaluate cancer specific survival of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

VI. To evaluate renal functional outcomes of patients treated with neoadjuvant systemic chemotherapy preceding nephroureterectomy.

TERTIARY OBJECTIVES:

I. To collect pre-treatment and post-treatment tumor tissue, peripheral blood mononuclear cell (PBMC), peripheral blood plasma, and urine specimens for potential evaluations of markers of chemotherapy response/resistance.

OUTLINE: Patients are assigned to 1 of 2 treatment arms based on baseline renal function.

ARM A (CREATININE CLEARANCE [CRCL] >= 50): Patients receive methotrexate intravenously (IV) over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.

ARM B (30 =< CRCL < 50): Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Localized Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter
  • Regional Urothelial Carcinoma of the Renal Pelvis and Ureter
Intervention  ICMJE
  • Drug: Methotrexate
    Given IV
  • Drug: Vinblastine
    Given IV
    Other Names:
    • Velban
    • Velsar
    • VLB
  • Drug: Doxorubicin Hydrochloride
    Given IV
  • Drug: Cisplatin
    Given IV
  • Drug: Gemcitabine Hydrochloride
    Given IV
    Other Names:
    • dFdC
    • dFdCyd
  • Drug: Carboplatin
    Given IV
  • Procedure: Therapeutic Conventional Surgery
    Undergo nephroureterectomy and lymph node dissection
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE
  • Experimental: Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)
    Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
    Interventions:
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin Hydrochloride
    • Drug: Cisplatin
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis
  • Experimental: Arm B (gemcitabine, carboplatin)
    Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
    Interventions:
    • Drug: Gemcitabine Hydrochloride
    • Drug: Carboplatin
    • Procedure: Therapeutic Conventional Surgery
    • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: July 25, 2018)
36
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2015)
60
Estimated Study Completion Date  ICMJE February 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have high grade upper tract urothelial carcinoma proven by one of the following:

    • Biopsy;
    • Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional imaging; or
    • Urinary cytology and a mass visualized during upper urinary tract endoscopy
  • Patients must have a creatinine clearance >= 30 ml/min as determined by Cockcroft-Gault calculation or 24-hour urine creatinine clearance measurement within 28 days of registration to be eligible for the study
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Patients must have no evidence of metastatic disease or clinically enlarged lymph nodes on computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis and CT chest obtained within 28 days of registration (a negative biopsy is required for lymph nodes > 1 cm in size to confirm lack of involvement); patients with lymph nodes > 1 cm in whom a biopsy is deemed not feasible are not eligible; patients with elevated alkaline phosphatase or suspicious bone pain should also undergo baseline bone scans to evaluate for bone metastasis
  • Patients with any component of small cell carcinoma are not eligible; other variant histologies are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
  • Patients must not have peripheral neuropathy > grade 2
  • Patients must not have a history of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
  • Patients must have a left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition [MUGA] or 2-dimensional [2-D] echocardiogram) within 28 days of registration
  • Absolute neutrophil count (ANC) >= 1500/mm^3
  • Platelets >= 100,000/mm^3
  • Hemoglobin (HgB) >= 9
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2 X institutional upper limit of normal (ULN)
  • Bilirubin within institutional normal limits (or < 2.5 X the ULN for patients with Gilbert's disease)
  • Patients with concomitant primaries of the bladder/urethra are allowed, as long as these sites are surgically resected and non-invasive cancers (< cT1N0)
  • Patients must not have another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer; patients that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment
  • For patients who have creatinine clearance that meets >= 50 ml/min they must not have received prior systemic doxorubicin
  • Patients with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction in last 3 months, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
  • Patients who are known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy are ineligible
  • Patients must have no prior radiation therapy to >= 25% of the bone marrow for other diseases or prior systemic anthracycline therapy; prior intravesical anthracycline therapy for non-muscle invasive urothelial carcinoma of the bladder is permitted
  • Patients may have a history of resectable urothelial cancer (including neoadjuvant chemotherapy) as long as patients meet one of the following:

    • pT0, Tis, or T1N0 and have no evidence of disease (NED) for more than 2 years from surgery or chemotherapy;
    • pT2-3aN0 and NED for more than 3 years from surgery or chemotherapy; or
    • > pT3b, or N+ and NED for more than 5 years from surgery or chemotherapy
  • Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02412670
Other Study ID Numbers  ICMJE EA8141
NCI-2014-02267 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA8141 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA8141 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )
Study Sponsor  ICMJE ECOG-ACRIN Cancer Research Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Vitaly Margulis ECOG-ACRIN Cancer Research Group
PRS Account Eastern Cooperative Oncology Group
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP