Content - SAKK 07/17

SAKK 07/17 - Treatment of kidney cancer using immunotherapy with nivolumab and ipilimumab

The aim of this study is to find out whether combined immunotherapy with nivolumab and ipilimumab in patients with advanced kidney cancer that cannot be treated surgically or has formed secondary tumours is effective and can stop the cancer growing or cause it to recede. We also want to find out which factors determine whether or not a patient responds to the medicines. For this reason we will be taking blood and tissue samples in addition to administering the treatment. These samples are important in finding out why the medication works. Nivolumab and ipilimumab have already been authorized singly for the treatment of kidney cancer. They can activate the immune system and in this way help to fight the cancer. Yet these treatments only work in a small proportion of patients. There is initial evidence that a combination of nivolumab and ipilimumab could have a better effect in more patients. We want to investigate this in more detail in this study. In SAKK 07/17 all patients will be given the same medicinal products. This means that all participants will benefit from a treatment that may be better. The treatment will last up to 2 years, depending on its effect.

Study Chairs:

Prof. Dr. med. Frank Stenner, University Hospital Basel, +41 61 265 50 74

Dr. med. Dr. phil. nat. Heinz Läubli, University Hospital Basel, +41 61 265 50

  • 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, 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-α blockers) within 30 days before registration.
  • Exceptions

    • 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.

Locations for this trial:

Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Inselspital
Freiburgstrasse 8
3010 Bern
Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Kantonsspital Baden
Im Ergel 1
4600 Baden
Kantonsspital Bruderholz
-
0 4101 Bruderholz
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Kantonsspital Winterthur
Brauerstrasse 15
0 8401 Winterthur
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich