RAD001 and Intravesical Gemcitabine in BCG-Refractory Primary or Secondary Carcinoma In Situ of the Bladder

NCT01259063 | Completed Phase 1 Results DMC

• 1 other identifier: 10-165
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to assess the right doses. Gemcitabine will be given at a fixed dose. Up to 3 dose levels of everolimus will be evaluated. The purpose of the phase II part is to test the combination of gemcitabine applied to the bladder directly combined with different oral doses of everolimus and to study the effects of these two drugs together. The investigators want to find out what effects, good and/or bad, this treatment has on the patient and the cancer.

Conditions

Bladder Cancer

Keywords

GEMCITABINE; RAD001(EVEROLIMUS); urinary; BCG-Refractory; Intravesical; 10-165

Outcome Measures

Primary Outcomes (3)

• Phase I - Dose-limiting Toxicity (DLT)

  Everolimus (mg) given in conjunction with intravesical gemcitabine

  8 weeks

• Phase II - Patients Who Are Free of Disease at 1 Year

  following start of therapy.

  1 year

• Phase I - Maximum Tolerated Dose (MTD)

  of Everolimus given in conjunction with intravesical gemcitabine

  8 weeks

Secondary Outcomes (3)

• Complete Response (CR) Rate

  1 year

• Survival of Patients Treated

  1 year

• Activated mTOR (Mammalian Target of Rapamycin) Pathway Markers as Well as Phosphatase and Tensin Homolog (PTEN) Status and Serine/Threonine Kinase (AKT) Activation Evaluation

  1 year

Study Arms (1)

Pts who failed or relapsed after intravesical BCG

EXPERIMENTAL

Phase I: Everolimus will be administered as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be administered at the dose determined in Phase .Everolimus will be continued for 12 months in the patients who achieve a CR or a Partial Response. Patients demonstrating a CR (by cystoscopy and cytology) or a Partial Response at their Cycle 12 cystoscopy will be observed with serial cystoscopies every 3 months.

Drug: Everolimus and Intravesical Gemcitabine

Interventions

Everolimus and Intravesical Gemcitabine DRUG

Phase I: Everolimus will be adm as follows: Dose level 1: 5 mg every other day, Dose level 2: 5 mg daily, Dose level 3: 10 mg daily Phase II: Everolimus will be adm at 10 mg daily the dose determined in Phase I. Pts will receive a dose of 2000 mg of intravesical gemcitabine twice a week (72-96 +8 hours between doses) for 3 weeks for a total of 6 treatments in course 1. After 1 week of rest from intravesical gemcitabine, course 2 will be administered, provided the treating physician notes acceptable pt tolerance. The total number of intravesical instillations will be 12. There will be no dose modifications to gemcitabine; however, pts will be allowed to skip gemcitabine doses if needed, per the treating physician's discretion. Missed or skipped doses of gemcitabine will not be repeated. The pt will receive as many instillations as tolerable up to the maximum of 12 instillations.

Pts who failed or relapsed after intravesical BCG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have Bacille Calmette-Guérin (BCG) refractory primary or secondary TisN0M0 BCG-refractory disease is defined as:
• Patient positive for Cis after 2 consecutive BCG installations
• OR, patient had a BCG response and failure within 6 months
• OR, patient has Cis on maintenance BCG
• OR, patient has persistent Cis 6 months after at least one instillation of BCG
• OR, patient is BCG intolerant
• OR, any of the above criteria for patients with a history of T1 disease
• OR, patient has BCG-relapsing disease, defined as failure more than 6 months after the patient was disease-free
• Pathologic confirmation of urothelial carcinoma by the enrolling institution
• Karnofsky Performance Status (KPS) ≥ 70%
• Age ≥ 18 years
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb \>9 g/dL
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5 x ULN (upper limit of normal)
• ALT and AST ≤ 2.5x ULN

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.) with the exception of topical anti-neoplastic agents that are not being used to treat malignancy
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study.
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period
• Other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin or adenocarcinoma of the prostate that has been treated.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• symptomatic congestive heart failure of New York Heart Association Class III or IV
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
• Severely impaired lung function as defined by spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
• active (acute or chronic) or uncontrolled severe infections including urinary tract infections
• liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small-bowel resection)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator
• New York University: collaborator
• University of Hawaii: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Guido Dalbagni
• Organization: Memorial Sloan Kettering Cancer Center

dalbagng@mskcc.org

646-422-4394

Study Officials

• Guido Dalbagni, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2010
• First Posted: December 13, 2010
• Study Start: December 1, 2010
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: March 13, 2018
• Results First Posted: March 13, 2018

Record last verified: 2017-06

Locations

US (1)