VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Stage III Bladder Cancer; Squamous Cell Carcinoma of the Bladder; Proximal Urethral Cancer; Adenocarcinoma of the Bladder; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Urethral Cancer Associated With Invasive Bladder Cancer; Stage III Urethral Cancer; Transitional Cell Carcinoma of the Bladder; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Bladder Cancer; Stage IV Bladder Cancer; Distal Urethral Cancer; Recurrent Urethral Cancer

Treatments: Biological: ziv-aflibercept; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00407485

N01CM62209 (U.S. NIH Grant/Contract)

7533 (Other Identifier)

NCI-2012-02840 (Registry Identifier)

N01CM62201 (U.S. NIH Grant/Contract)

PHII-76 (Other Identifier)

Details and patient eligibility

About

This phase II trial is studying the side effects and how well VEGF Trap works in treating patients with recurrent, locally advanced, or metastatic cancer of the urothelium. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor.

Full description

PRIMARY OBJECTIVES:

I. Determine the response rate in patients with recurrent, locoregionally advanced, or metastatic transitional cell carcinoma of the urothelium treated with VEGF Trap.

II. Determine the time to progression in patients treated with this drug. III. Determine overall survival of patients treated with this drug. IV. Determine the tolerability and safety of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection periodically during study for pharmacokinetic/pharmacodynamic correlative studies.

After completion of study treatment, patients are followed periodically.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed transitional cell carcinoma (TCC) of the urothelium

  • Must have predominance of transitional histology, but foci of squamous and/or adenocarcinoma histology allowed
  • Poorly differentiated transitional cell carcinoma allowed

• TCC of any of the following sites allowed:

  • Bladder
  • Renal pelvis
  • Ureter
  • Urethra

• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan

• Locoregionally advanced or metastatic disease that is not amenable to curative surgery and/or radiotherapy

• Must have received 1 prior systemic chemotherapy regimen containing a platinum compound (e.g., cisplatin, carboplatin, or oxaliplatin) in the neoadjuvant, adjuvant, or metastatic setting

• No evidence of CNS disease, including primary brain tumor or brain metastases

• ECOG performance status 0-2

• Absolute neutrophil count >= 1,000/mm^3

• Platelet count >= 75,000/mm^3

• Bilirubin =< 1.5 times upper limit of normal (ULN)

• AST or ALT =< 2.5 times ULN

• Creatinine =< 2.5 times ULN OR creatinine clearance => 40 mL/min

• Urine protein: creatinine ratio =< 1 OR 24-hour urine protein < 500 mg

• INR =< 1.5 (unless on full-dose warfarin)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for >= 6 months after completion of study treatment

• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

• No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study

• No serious or nonhealing wound, ulcer, or bone fracture

• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

• No significant traumatic injury within the past 28 days

• No clinically significant cardiovascular disease, including any of the following:

  • Myocardial infarction, coronary artery bypass graft, or unstable angina pectoris within the past 6 months
  • New York Heart Association class III or IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
  • Clinically significant peripheral vascular disease within the past 6 months
  • Cerebrovascular accident within the past 6 months
  • Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
  • Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg (if diastolic BP < 90 mm Hg) within the past 3 months

• No evidence of bleeding diathesis or coagulopathy

• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

  • Ongoing or active infection
  • Psychiatric illness or social situation that would preclude study compliance

• Recovered from prior therapy

• Prior biologic or targeted therapies allowed

• No more than 1 prior systemic chemotherapy regimen for metastatic disease

• No prior antiangiogenic therapy primarily targeting the vascular endothelial growth factor pathway

• At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for mitomycin C or nitrosoureas)

• More than 28 days since prior major surgery or open biopsy

• More than 7 days since prior core biopsy

• No concurrent major surgery

• Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the following criteria are met:

  • In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or low molecular weight heparin
  • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for HIV-positive patients

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Treatment (ziv-aflibercept)

Experimental group

Description:

Patients receive 4 mg/kg VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: pharmacological study

Biological: ziv-aflibercept