Study of Gemcitabine, Carboplatin, and Panitumumab (GCaP) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Gemcitabine; Carboplatin; Panitumumab; radical cystectomy
Intervention MeSH terms: Carboplatin; Gemcitabine; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gemcitabine; Carboplatin; Panitumumab; (GCaP); radical cystectomy; 10-103

Summary:

      The purpose of this study is to find out if using the combination of standard chemotherapy
      (gemcitabine and carboplatin) plus this new drug (panitumumab) can help to shrink the tumor
      before the patient undergoes surgery for bladder cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed muscle invasive transitional cell carcinoma of the bladder at
             MSKCC (Note: urothelial carcinoma invading into the prostatic stroma with no
             histologic muscle invasion is allowed, provided the extent of disease is confirmed via
             imaging and/or EUA.)

          -  Clinical stage T2-T4a N0/X M0 disease.

          -  Medically appropriate candidate for radical cystectomy as per MSKCC attending urologic
             oncologist

          -  Karnofsky Performance Status ≥ 80%

          -  Age ≥ 18 years of age

          -  Required Initial Laboratory Values:

        Absolute neutrophil count ≥ 1500 cells/mm3

          -  Platelets ≥ 100,000 cells/mm3

          -  Hemoglobin ≥ 9.0g/dL

          -  Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution

          -  Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the
             institution

          -  Alkaline phosphatase ≤ 2.5 x ULN for the institution

          -  Serum magnesium > 1.4 mEq/L

          -  Serum creatinine ≤ 2.0 mg/dL

          -  Cisplatin ineligibility based on one or more of the following criteria:

        Estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73m2 using the CKD-EPI
        equation:(http://nephron.org/MDRD_GFR.cgi) :

        eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age x 1.018 [if female] x 1.159
        [if black] Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for
        females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates
        the maximum of Scr/k or 1.

          -  Grade 2 sensory neuropathy

          -  Grade 2 hearing loss

               -  Patients must provide a pretreatment saliva sample for genomic analysis.

        Exclusion Criteria:

          -  Prior systemic chemotherapy (prior intravesical therapy is allowed)

          -  Serious intercurrent medical or psychiatric illness.

          -  Prior radiation therapy to the bladder.

          -  Concomitant use of any other investigational drugs

          -  Any of the following within the 6 months prior to study drug administration:
             myocardial infarction, grade 2 or greater peripheral vascular disease, arterial
             thrombotic event, visceral arterial ischemia, cerebrovascular ischemia, transient
             ischemic attack, percutaneous transluminal angioplasty or stent, or unstable angina.

        Symptomatic and/or serious uncontrolled arrhythmia

          -  Symptomatic congestive heart failure (NYHA class III or IVI)

          -  History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
             evidence of interstitial lung disease on baseline chest CT scan.

          -  History of any medical or psychiatric condition or laboratory abnormality that in the
             opinion of the investigator may increase the risk associated with the study
             participation or investigational product(s) administration or may interfere with the
             interpretation of the results.

          -  Major surgery requiring general anesthesia within 21 days or minor surgery within 14
             days of study enrollment. Subjects must have recovered from surgery related
             toxicities.

          -  Pulmonary embolism, deep vein thrombosis, or other significant venous event ≤ 8 weeks
             before enrollment

          -  Known allergy or hypersensitivity to any component of the study treatment(s)

          -  Active infection requiring systemic treatment or any uncontrolled infections ≤14 days
             prior to enrollment.

          -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
             (AIDS)-related illness.

          -  Concurrent treatment on another clinical trial. Supportive care trials, surgical
             clinical trials or non-treatment trials, e.g. QOL, are allowed.

          -  Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg po
             daily for thromboembolic prophylaxis is allowed).

          -  Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal,
             or must agree to use effective contraception during the period of therapy and for two
             (2) months following the last dose of panitumumab. The definition of effective
             contraception will be based on the judgment of the principal investigator or a
             designated associate. Male patients must be surgically sterile or agree to use
             effective contraception.