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

NCT ID: NCT01663285

Last Updated: 2015-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2014-01-31

Brief Summary

The main purpose of this study is to look at the cancer-free survival at two years of subjects with high risk upper tract urothelial cancer when treated with the combination of two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the kidney, all or part of the ureter (ureters are tubes made of smooth muscle fibers that propel urine from the kidneys to the urinary bladder), and a cuff of bladder where the ureter drains into the bladder. Other purposes of the study include looking at the safety of Gemcitabine and Cisplatin before surgery for this type of cancer, time to recurrence of cancer, and overall survival.

Exploratory integrative tumor sequencing:

The purpose of this part of the study is to test deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) in various types of samples (tissue and blood) to detect different types of cancer genetic changes in upper tract urothelial cancer (UTUC) to help develop future studies in UTUC. DNA and RNA contain key instructions for cell function and help determine the characteristics of each individual such as hair, eye, and skin color, height, susceptibility to diseases, and other characteristics.

Detailed Description

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.

Conditions

Urothelial Cancer; Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant Gemcitabine and Cisplatin

Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.

Group Type: EXPERIMENTAL

Neoadjuvant Cisplatin and Gemcitabine

Intervention Type: DRUG

Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.

Interventions

Neoadjuvant Cisplatin and Gemcitabine

Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.

Intervention Type: DRUG

Eligibility Criteria

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 registration.
• Patients must have adequate organ and bone marrow function as determined by screening tests
• Patients must have recovered from any reversible toxicities of prior procedure or surgery
• 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 imaging.
• 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 registration.
• 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 allowed.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajjai S. Alva, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

University of Rochester

Rochester, New York, United States

Oregon Health Sciences University

Portland, Oregon, United States

Countries

United States

Other Identifiers

HUM00062285

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2012.038

Identifier Type: -

Identifier Source: org_study_id