Gemcitabine and Pazopanib in Chemotherapy Naïve Patients With Advanced/Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Chemotherapy

NCT01622660 | Terminated Phase 2 Results

• 1 other identifier: 11-191
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 5

Brief Summary

Gemcitabine and Cisplatin are standard chemotherapy drugs used to treat advanced urothelial cancer. There is no standard chemotherapy for patients who cannot receive Cisplatin. However, most patients are treated with the chemotherapy drugs Gemcitabine and Carboplatin. In this study, the researchers hope to learn what effects, good and/or bad, the combination of Gemcitabine and Pazopanib has on urothelial cancer. Gemcitabine is given intravenously (through the veins) and works by killing rapidly dividing cells in the body, including cancer cells. Pazopanib is an oral chemotherapy and works by decreasing the blood supply to tumors which limits the tumor's source of oxygen and nutrients. The combination of Gemcitabine and Pazopanib is being tested in research studies such as this one. As of August 2011, more than 18 patients with various types of cancer have received treatment with Gemcitabine and Pazopanib. The main goal of this clinical research study is to learn if the study drugs Gemcitabine and Pazopanib can shrink or slow the growth of urothelial cancer. The safety of this drug will also be studied. The physical state, changes in the size of the tumor, and laboratory findings will help us decide if the combination of Gemcitabine and Pazopanib is safe and effective.

Conditions

Bladder Cancer

Keywords

URETER; URINARY BLADDER; renal pelvis; GEMCITABINE; GW786034 (PAZOPANIB); 11-191

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression Free Survival will be calculated from the start of treatment until progressive disease or death. Patients who die before documented progression will be considered failures at their time of death. If the patient did not progress or die, the patient will be censored on the date of last follow-up. Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Measurable lesions: lesions that can be accurately measured in at least one dimension with longest diameter ≥ 10 mm by clinical exam or with spiral CT scan or MRI (no less than double the slice thickness and a minimum of 10mm). Malignant lymph nodes must be 15 mm in the short axis when assessed by spiral CT scan to be considered measurable. Non-measurable lesions: all other lesions (or sites of disease) including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm u

  2 years

Study Arms (1)

Gemcitabine and Pazopanib

EXPERIMENTAL

This is a phase II trial of gemcitabine and pazopanib in previously untreated patients with advanced/metastatic urothelial carcinoma (UC) who are ineligible for cisplatin-based chemotherapy.

Drug: Gemcitabine; Drug: Pazopanib

Interventions

Gemcitabine DRUG

Patients will receive gemcitabine 1200 mg/m2 intravenously on day 1 and day 8 and. Patients will receive 6 cycles of combination therapy (gemcitabine and pazopanib) unless disease progression or unacceptable toxicity occurs. Patients that achieve stable disease, a partial response, or a complete response after completion of 6 cycles, and who are not candidates for consolidation surgery, will be eligible to continue pazopanib monotherapy at the same dose and schedule until disease progression for a maximum of 18 additional cycles.

Gemcitabine and Pazopanib

Pazopanib DRUG

pazopanib 800 mg orally daily day 1 through day 21 (1 cycle = 21 days) Patients will receive 6 cycles of combination therapy (gemcitabine and pazopanib) unless disease progression or unacceptable toxicity occurs. Patients that achieve stable disease, a partial response, or a complete response after completion of 6 cycles, and who are not candidates for consolidation surgery, will be eligible to continue pazopanib monotherapy at the same dose and schedule until disease progression for a maximum of 18 additional cycles.

Gemcitabine and Pazopanib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis by MSKCC pathology review
• Measurable disease as determined by RECIST v1.1 on initial pretreatment staging CT scan of the chest, abdomen, and pelvis (or MRI if clinically appropriate). (Note: A chest x-ray may be performed as an alternative to a CT scan of the chest.)
• Ineligible for cisplatin based on one or more of the following:
• Calculated creatinine clearance of \< 60 mL/min (but ≥ 30 mL/min)
• Karnofsky Performance Status (KPS) 60-70% (ECOG PS 2)
• Grade 2 ≥ hearing loss
• Grade 2 ≥ peripheral neuropathy
• Karnofsky Performance Status ≥ 60%
• unstained slides or paraffin embedded tissue block obtained from pretreatment tumor specimens for immunohistochemistry. (Note: One paraffin block or 10 freshly-prepared unstained slides from the most representative single paraffin embedded tumor tissue block should be submitted. Slides from the primary tumor are preferred. If both the primary and metastatic tumor blocks are available, 10 slides from each of the sites should be submitted. If tissue from the primary tumor is not available, a paraffin block or unstained slides from a metastatic site are acceptable. Fine needle aspirates (FNAs) have insufficient tumor tissue and are not permitted.)
• Adequate organ system function as defined:
• Absolute neutrophil count (ANC) ≥1.5 X 109/L
• Hemoglobin ≥9 g/dL (5.6 mmol/L) (Note: Subjects may not have had a transfusion within 7 days of screening assessment.)
• Platelets ≥100 X 109/L
• Prothrombin time (PT) or international normalized ratio (INR) ≤1.2 X ULN (Note: Subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation.)

You may not qualify if:

• Prior treatment with systemic chemotherapy (prior intravesical therapy is permitted)
• Prior malignancy (Note: Subjects who have had another malignancy and have been disease-free for 5 years subjects with a history of completely resected non-melanomatous skin carcinoma, subjects with successfully treated in situ carcinoma, or subjects who have had adenocarcinoma of the prostate that has been definitively treated with a post-treatment PSA that is non-detectable are eligible.)
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) is required only if clinically indicated or if the subject has a history of CNS metastases.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel
• Active liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
• Presence of uncontrolled infection Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• o If QTc interval is \> 480 msecs, then 2 additional ECGs should be obtained over a brief period of time (e.g., within approximately 15-20 minutes) to confirm the abnormality. The average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the subject will be excluded from the study. If the average QTc interval is \>480 msec, then the subject is not eligible to participate in the study Previous history of QTc prolongation as a result of other medication that required discontinuation of that medication
• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
• Use of any concomitant medication (during treatment with pazopanib or within 14 days of starting treatment) that are high risk for QTc prolongation or may induce Torsades de Pointes.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center at Mercy Medical Center

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, 10591, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Gemcitabine; pazopanib

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)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Dean Bajorin
• Organization: Memorial Sloan Kettering Cancer Center

bajorind@mskcc.org

646-422-4333

Study Officials

• Dean Bajorin, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2012
• First Posted: June 19, 2012
• Study Start: June 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: August 22, 2017
• Results First Posted: August 22, 2017

Record last verified: 2017-05

Locations

US (5)