SAKK 07/17 - Behandlung von Nierenkrebs durch Immuntherapie mit Nivolumab und Ipilimumab

Drug: nivolumab;Drug: ipilimumab

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

- Written informed consent according to Swiss law and ICH/GCP regulations before
registration and prior to any trial specific procedures

- Histologically or cytologically confirmed, locally advanced and/or metastatic clear
cell RCC not amenable to surgery or definitive radiotherapy, and requiring systemic
therapy

- Patient able and willing to provide serial biopsies and blood drawings (initial, at 14
weeks (except for patient in the expansion cohort), and at progression).

- Measurable disease

- In case of second line patients, the previous therapy must be stopped at least 2 weeks
prior to registration

- Age = 18 years

- WHO performance status of 0-1

- Bone marrow function: neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L

- Hepatic function: total bilirubin = 1.5 x ULN (except for patients with Gilbert's
disease = 3.0 x ULN), AST, ALT and AP = 2.5 x ULN (= 5 x ULN if significant hepatic
metastasis is suspected to be the cause for enzyme elevation)

- Renal function: eGFR > 20 mL/min/1.732

- Cardiac function: NYHA = 2. In case of cardiac insufficiency NYHA 1 or 2, Left
ventricular Ejection Fraction (LVEF) = 35% as determined by echocardiography (ECHO) or
multigated acquisition (MUGA) scan

- Women with child-bearing potential are using effective contraception are not pregnant
or lactating and agree not to become pregnant during trial treatment and during 5
months thereafter. A negative pregnancy test before inclusion into the trial is
required for all women with child-bearing potential.

- Men agree not to father a child during trial treatment and during 5 months thereafter

Exclusion Criteria:

- Uncontrolled CNS metastases. Patients with asymptomatic CNS metastases (at least 2
weeks after radiotherapy or surgery and steroids with prednisone equivalent of 10 mg
or lower) are eligible

- History of hematologic or primary solid tumor malignancy, unless in remission for at
least 3 years from registration with the exception of pT1-2 prostate cancer Gleason
score < 6, adequately treated cervical carcinoma in situ, or localized non-melanoma
skin cancer.

- More than one previous line of systemic therapy for mRCC

- Prior immunotherapy.

- Concurrent or recent (within 30 days of registration) treatment with any other
experimental drug

- Concomitant use of other anti-cancer drugs or radiotherapy except for local pain
control (radiotherapy of target lesion not allowed)

- Immunosuppressive medications (such as but not limited to: methotrexate, azathioprine,
and TNF-a blockers) within 30 days before registration

Exception:

- systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or equivalent

- immunosuppressive medications for patients with contrast allergies

- inhaled and intranasal corticosteroids

- Live attenuated vaccination within 30 days prior to registration and for 30 days after
last dose of any of the trial drugs. Inactivated viruses, such as those in the
influenza vaccine, are permitted

- History of or active auto-immune disease with the exception of diabetes mellitus type
II

- Human immunodeficiency virus (HIV) infection or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment

- Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.