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Phase II Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)

Phase 2
18 Years
Open (Enrolling)
Urothelial Cancer, Bladder Cancer

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Trial Information

Phase II Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)

In recent years, the combination of gemcitabine and cisplatin given every 21 days
(gemcitabine on days 1 and 8 only) has been used in trials and routine clinical practice.
Additionally, surgery, primarily radical nephroureterectomy (RNU) with bladder cuff removal,
is the current standard treatment for invasive upper tract urothelial carcinoma.

Upper tract urothelial cancer (UTUC) or urothelial cancer arising in the pelvicalyceal or
ureteral locations is a lethal cancer accounting for 5% of all urothelial cancers. In
urothelial cancer of the bladder, randomized clinical trials and meta-analyses have shown a
survival advantage with neoadjuvant cisplatin-based chemotherapy. It is conceivable that a
similar approach may benefit patients with UTUC.

Both Gemcitabine and Cisplatin are approved by the FDA. Cisplatin is approved for use in
urothelial cancer. Gemcitabine is FDA approved to be used alone or with other drugs to
treat breast, non-small lung, ovarian, and pancreatic cancers. Gemcitabine is not approved
by the FDA for urothelial cancer, but it is typically used together with Cisplatin in trials
and routine clinical practice for treating urothelial cancer.

Exploratory integrative tumor sequencing:

The biology of UTUC is poorly understood due to the relative rarity of the disease and the
lack of comprehensive genomic and translational studies. This trial offers a rare
opportunity to apply high-throughput sequencing techniques in UTUC to detect several classes
of cancer mutations including structural rearrangements, copy number alterations, point
mutations, and gene expression alterations. This research could help to develop future
studies in UTUC to help researchers understand more about UTUC and how to treat it.
Additionally, we may identify a potentially important result from DNA samples from subjects
that could possibly help manage their cancer better by pursing a different cancer therapy
rather than the study therapy.

Inclusion Criteria:

- Patients must have HIGH GRADE upper tract urothelial carcinoma

- Patients must be considered to be a candidate for surgery with curative intent
(nephroureterectomy or distal ureterectomy) with lymph node dissection by the
treating urologist at baseline within 42 days prior to registration.

- Patients must be able to care for themselves and must be up and about more than 50%
of waking hours

- All patients must be evaluated by a medical oncologist at baseline within 42 days
prior to registration. Patients must be considered to be a candidate for
cisplatin-based neoadjuvant chemotherapy by a medical oncologist at baseline and must
have adequate kidney function and any pre-existing peripheral neuropathy must be
moderate to mild.

- Prior uro-oncologic history:

- History of or active non-invasive carcinoma or carcinoma in situ of the bladder
or upper tract is allowed.

- Patients may have received prior intravesical chemotherapy or immunotherapy such
as BCG.

- Prior neoadjuvant chemotherapy for bladder cancer or invasive contralateral
upper tract cancer is allowed.

- Prior adjuvant chemotherapy for bladder cancer or invasive contralateral upper
tract cancer is allowed but must have been completed ≥2 years prior to study

- Patients must have adequate organ and bone marrow function as determined by screening

- Patients must have recovered from any reversible toxicities of prior procedure or

- Patients must be 18 years or older on date of registration

- All patients must be informed of the investigational nature of this study and must
sign an informed consent document

Exclusion Criteria:

- Patients must have no evidence of regional lymphadenopathy or distant metastasis on

- No history of invasive or node positive or metastatic bladder cancer or invasive
contralateral upper tract cancer within 2 years prior to registration.

- Patients with one kidney are not eligible

- Patients may not be enrolled in another interventional clinical trial at the time of

- No prior non-urothelial malignancy is allowed, except for cancer from which the
patient has been disease free for at least 1 year at the discretion of the treating
oncologist. History of adequately treated (at the discretion of the treating
oncologist) basal cell or squamous cell skin cancer or in situ cervical cancers is

- Pregnant or lactating women are not eligible. Women/men of reproductive potential
must agree to use an effective contraceptive method. Women with reproductive
potential must have a negative pregnancy test within 14 days prior to registration.

- Patients must not have any other medical condition(s) that make(s) their
participation in the study unadvisable in the opinion of the treating oncologist.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Recurrence-free survival

Outcome Description:

The 2-year recurrence-free survival (RFS) rate of patients treated with neoadjuvant cisplatin and gemcitabine chemotherapy followed by surgery in high risk upper tract urothelial carcinoma.

Outcome Time Frame:

2 years after participant surgery

Safety Issue:


Principal Investigator

Ajjai S. Alva, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan


United States: Institutional Review Board

Study ID:

UMCC 2012.038



Start Date:

September 2012

Completion Date:

August 2021

Related Keywords:

  • Urothelial Cancer
  • Bladder Cancer
  • Urothelial
  • Bladder
  • Cancer
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Transitional Cell



Baylor College of MedicineHouston, Texas  77030
University of MichiganAnn Arbor, Michigan  48109-0624
University of UtahSalt Lake City, Utah  
Oregon Health Sciences UniversityPortland, Oregon  
University of RochesterRochester, New York  14642
University of Southern CaliforniaLos Angeles, California  90033