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Study Summary
No. 2006-0080:.......Bladder......Padmanee Sharma......Genitourinary Medical Oncology
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Study Summary Title
Study Summary
Number:
2006-0080
Study Title:A Phase 1b Safety and Dose-Assessment Study of Neoadjuvant Ipilimumab Monotherapy in Patients with Urothelial Carcinoma Undergoing Surgical Resection.(CA184027)
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Physician New Patient Referral
Name:Padmanee SharmaPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Genitourinary Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2830
Contact us about clinical trials
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General Information
Disease Group:BladderSupported By:N/A
Phase of Study:Phase IReturn
Visit:
Patients will be required to return at Week 4 and Week 7 while on treatment.
The participants will have surgery during Week 8 and will return for follow-up
once between Weeks 12-16 and at Week 24.
Treatment
Agents:
MDX-010Home Care:N/A
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
Participants will be hospitalized to undergo schedule surgery to remove the
disease site.
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
(from 2 established dose levels) of ipilimumab that can be given to patients
with bladder cancer who are scheduled for cystectomy and/or
nephroureterectomy. Researchers also want to study the safety and effectiveness
of this drug.
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Study Objectives / Outcomes
Primary Objective:
To characterize the safety profile and serious drug related adverse events of two of the established
doses of ipilimumab and select a favorable and tolerable dose as a neoadjuvant monotherapy for patients
with urothelial carcinoma undergoing surgical resection.

Secondary Objectives:
1. To obtain an early gauge of anti-cancer immunological activity by evaluating blood and surgical specimens for evidence of post-treatment lymphocytic infiltration (e.g. presumed immune response) compared to pre-treatment blood and biopsy samples or control untreated, banked tumor tissues from comparable patients.
    • To perform immunohistochemistry (IHC) and fluorescence activated cell sorting (FACS) analyses on obtained samples for comparison of ratio and total numbers of effector CD4+, effector CD8+, and regulatory FOXP3+ T cell populations.
    • To perform reverse transcription polymerase chain reaction (RT-PCR) and mRNA analysis obtained from tumor tissues for identification and comparison of cytokines such as TNF-alpha, IFN-gamma, GM-CSF, TGF-beta, IL-10, and IL-6.

2. To perform ELISA and ELISPOT analyses on obtained samples to characterize humoral and T cell responses to tumor antigens such as cancer-testis antigens.
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Study Status Information
Study Activation / Registration Date:03/09/2007
IRB Review and Approval Date:03/09/2007
Study Type:Phase I
Recruitment Status:Terminated
Projected Accrual:N/A
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Willing and able to give written informed consent.

2) Histologic diagnosis of urothelial carcinoma by MDACC Pathology review.

3) Patients with TaN0M0, TisN0M0, or T1N0M0 who require surgery for treatment of disease.

4) Patients with T2N0M0 disease without lymphovascular invasion or micropapillary features on pathology and who do not require neoadjuvant chemotherapy as determined by the treating physician.

5) Patients with T2N0M0 or T3N0M0 who cannot receive cisplatin-based neoadjuvant chemotherapy due to poor renal function (calculated CrCl < 40ml/min) or who refuse neoadjuvant chemotherapy.

6) Patient eligible for surgery consisting of cystectomy and/or nephroureterectomy.

7) ECOG performance status of 0 or 1.

8) Required values for initial laboratory tests: • WBC >/= 2500/uL • ANC >/= 1000/uL • Platelets >/= 75 x 10^3/uL • Hemoglobin >/= 9 g/dL • Creatinine </= 2.5 x ULN • AST </= 3 x ULN • Bilirubin </= 3 x ULN

9) Men and women, ages >/= 18 of age.

10) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as:

11) (# 10 Cont'd) Amenorrhea >/= 12 consecutive months without another cause or; For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >/= 35mIU/mL]. Women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential.

12) ( # 10 Cont'd) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.

Exclusion Criteria:1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study.

2) Women who are pregnant or breastfeeding.

3) Women with a positive pregnancy test on enrollment or prior to study drug administration.

4) Sexually active fertile men whose partners are woman of child bearing potential, unless using an adequate method of birth control.

5) Prior treatment with an anti-CTLA4 antibody.

6) Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, or carcinoma in situ of the cervix.

7) Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]).

8) Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.

9) Positive screening tests for or any prior history of Active or chronic infection with HIV, Hepatitis B, or Hepatitis C.

10) Patients who are deemed ineligible for surgery after standard of care evaluation for medical comorbidities.

11) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).

12) Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses).

13) Previous participation in another ipilimumab clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist.

14) Treatment with other investigational products within the last 4 weeks prior to randomization into this study.

15) Prior radiation therapy for urothelial carcinoma.

16) Prior systemic chemotherapy for urothelial carcinoma.

17) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.

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Links
Registration Number: NCT00362713
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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