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

Primary Purpose

Urothelial Cancer, Bladder Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Neoadjuvant Cisplatin and Gemcitabine

About this trial

This is an interventional treatment trial for Urothelial Cancer focused on measuring Urothelial, Bladder, Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Michigan
University of Rochester
Oregon Health Sciences University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neoadjuvant Gemcitabine and Cisplatin

Arm Description

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.

Outcomes

Primary Outcome Measures

Recurrence-free Survival Time

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

Secondary Outcome Measures

Number of Patients With Pathologic T0/Tis/Ta N0.

The proportion of patients with pathologic T0/Tis/Ta N0.

Number of Participants With Adverse Events

The safety of neoadjuvant chemotherapy.

Full Information

NCT ID

NCT01663285

First Posted

July 24, 2012

Last Updated

November 4, 2015

Sponsor

University of Michigan Rogel Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT01663285

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Terminated

Why Stopped

Low study participant enrollment.

Study Start Date

September 2012 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

January 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urothelial Cancer, Bladder Cancer

Keywords

Urothelial, Bladder, Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant Gemcitabine and Cisplatin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Neoadjuvant Cisplatin and Gemcitabine

Intervention Description

Primary Outcome Measure Information:

Title

Recurrence-free Survival Time

Description

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

Time Frame

2 years after participant surgery

Secondary Outcome Measure Information:

Title

Number of Patients With Pathologic T0/Tis/Ta N0.

Description

The proportion of patients with pathologic T0/Tis/Ta N0.

Time Frame

51 months

Title

Number of Participants With Adverse Events

Description

The safety of neoadjuvant chemotherapy.

Time Frame

9 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ajjai S. Alva, M.D.

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

University of Rochester

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

Oregon Health Sciences University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

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

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