NCT02412670|CompletedPhase 2ResultsFDA Drug

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

A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma

ECOG-ACRIN Cancer Research Group ClinicalTrials.gov

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3 other identifiers

EA8141NCI-2014-02267U10CA180820

Study Type

interventional

Target

Locations

1 country

Sites

134

Timeline

RegisteredApr 2015

StartedAug 2015

CompletionMay 2022

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_2

Timeline

Completed

Started Aug 2015

Longer than P75 for phase_2

Geographic Reach

1 country

134 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.7 years study duration

First Submitted

Initial submission to the registry

April 6, 2015

Completed

3 days until next milestone

First Posted

Study publicly available on registry

April 9, 2015

Completed

5 months until next milestone

Study Start

First participant enrolled

August 27, 2015

Completed

3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 23, 2018

Completed

2.4 years until next milestone

Results Posted

Study results publicly available

January 20, 2021

Completed

1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 10, 2022

Completed

Last Updated

July 10, 2023

Status Verified

June 1, 2023

Enrollment Period

3 years

First QC Date

April 6, 2015

Results QC Date

December 2, 2020

Last Update Submit

June 21, 2023

Conditions

High Grade Upper Tract Urothelial Carcinoma

Keywords

carcinomadrug therapynephroureterectomyurinary tracturothelium

Outcome Measures

Primary Outcomes (1)

Complete Pathologic Response Rate
Complete pathologic response is defined as pT0pN0 (no evidence of disease) as assessed by pathologic evaluation of nephrectomy/ureterectomy and any identifiable regional lymph nodes.
Assessed at nephroureterectomy or regional lymph node dissection (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

Secondary Outcomes (6)

Recurrence-free Survival
Assessed every 3 months for 2 years; and every 6 months for 3-5 years
Event-free Survival
Assessed every 3 months for 2 years, and every 6 months for 3-5 years
Bladder Cancer-free Survival
Assessed every 3 months for 2 years, and every 6 months for 3-5 years
Cumulative Incidence of Cancer-specific Death at 24 Months
Assessed every 3 months for 2 years
Proportion of Patients With Renal Insufficiency at Completion of Chemotherapy
Assessed at completion of chemotherapy; at 8 weeks for Arm A and 12 weeks for Arm B
+1 more secondary outcomes

Study Arms (2)

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

EXPERIMENTAL

Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. 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.

Drug: MethotrexateDrug: VinblastineDrug: DoxorubicinDrug: CisplatinDrug: PegfilgrastimProcedure: Nephroureterectomy

Arm B (gemcitabine, carboplatin)

EXPERIMENTAL

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.

Drug: GemcitabineDrug: CarboplatinProcedure: Nephroureterectomy

Interventions

MethotrexateDRUG

Given IV

Also known as: Folex, abitrexate, mexate

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

VinblastineDRUG

Given IV

Also known as: vinblastine sulfate

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

DoxorubicinDRUG

Given IV

Also known as: Adriamycin R, Rubex R, Adriamycin RDF R, Adriamycin PFS R, hydroxydaunorubicin, hydroxydaunomycin, ADR

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

CisplatinDRUG

Given IV

Also known as: Cisdiaminedichloroplatinum, Cis-diaminedichloroplatinum (II), diaminedichloroplatinum, cis-platinum, platinum, Platinol, Platinol-AQ, DDP, CDDP, DACP, NSC 119875

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

GemcitabineDRUG

Given IV

Also known as: 2'-Deoxy-2', 2'-difluorocytidine monohydrochloride, Gemzar

Arm B (gemcitabine, carboplatin)

CarboplatinDRUG

Given IV

Also known as: Paraplatin

Arm B (gemcitabine, carboplatin)

PegfilgrastimDRUG

Administered subcutaneously

Also known as: Neulasta

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)

NephroureterectomyPROCEDURE

Undergo nephroureterectomy and lymph node dissection

Arm A (methotrexate, vinblastine, doxorubicin, cisplatin)Arm B (gemcitabine, carboplatin)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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 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 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;
+3 more criteria

You may not qualify if:

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
Any component of small cell carcinoma; other variant histologies are permitted provided the predominant (\>= 50%) subtype is urothelial carcinoma
Peripheral neuropathy \> grade 2
History of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride), carboplatin or filgrastim or pegfilgrastim
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
Prior systemic doxorubicin for patients who have creatinine clearance that meets \>= 50 ml/min
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
Known to have human immunodeficiency virus (HIV) or are on combination antiretroviral therapy
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
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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

ECOG-ACRIN Cancer Research Grouplead
National Cancer Institute (NCI)collaborator

Study Sites (134)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Memorial Hospital Colorado Springs

Colorado Springs, Colorado, 80909, United States

Location

Poudre Valley Hospital

Fort Collins, Colorado, 80524, United States

Location

Saint Francis Hospital and Medical Center

Hartford, Connecticut, 06105, United States

Location

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Christiana Gynecologic Oncology LLC