Content - SAKK 11/16

SAKK 11/16 – Stimulating the immune system to fight against squamous cell carcinoma.

In the SAKK 11/16 trial we are investigating whether the immunotherapy MVX-ONCO-1 is effective, safe and tolerable in cases of advanced squamous cell carcinoma of the head and neck area. This immunotherapy consists of dead tumour cells from the patient and genetically modified cells in a capsule. For this, the patient’s own tumour cells are removed, killed in a laboratory and processed into a vaccine. This is then administered during the treatment. The immune system reacts to it and forms antibodies against the tumour cells, which helps the immune system to attack and destroy the tumour itself. The genetically modified cells release adjuvants which additionally stimulate the immune system.

Immunotherapy with MVX-ONCO-1 has only been tested in humans in a small Phase I trial. However, the individual components of this immunotherapy, the patient’s own tumour cells, the genetically modified cells and the capsules have been tested in multiple clinical trials.

  • Inclusion Criteria

    • Written informed consent according to ICH/GCP regulations before pre-registration
    • Histologically confirmed diagnosis of head and neck squamous carcinoma (oral cavity, pharynx, larynx), Stage III/IV in recurrent or metastatic stage with disease progression. Patients with local relapse for whom a curative treatment is available cannot be enrolled. Furthermore, all patients should have no other therapeutic option left.
    • One line of prior platinum-based chemotherapy with or without cetuximab for recurrent or metastatic disease
      • Note: Patients with prior anti-PD-1, anti-PD-L1, and anti-PD-L2 treatment can also be included
      • Note: Patients not fit for platinum-based chemotherapy can also be included.
      • Note: Patients with locally advanced disease experiencing local relapse within 6 months of last dose of curative intended, platinum-based chemo-radiation with or without prior surgery can also be included
    • Primary tumor and/or metastasis amenable for partial/total surgery or tap and subsequent cell harvest estimate > 31x106 cells
    • Measurable or evaluable disease according to RECIST 1.1 and irRC criteria (see Appendix 1 and 2)
    • Patients age ≥ 18 years
    • WHO performance status 0-2 (see Appendix 4)
    • Adequate hematological values: neutrophils≥1.5x109/L, platelets ≥100x109/L
    • Adequate hepatic function: bilirubin ≤2 x ULN; AST and ALT and AP ≤ 2.5 x ULN (except for patients with liver metastasis: ≤5 x ULN)
    • Adequate renal function (creatinine clearance >50mL/min/1.73m2, calculated according to the corrected formula of Cockcroft-Gault (see Appendix 3)
    • Foreign protein DTH test positive (≥ 5mm in the longest diameter) to at least one antigen (see Appendix 6)
    • Women with child-bearing potential are using effective contraception (see 9.9), are not pregnant or lactating and agree not to become pregnant during trial treatment and during the 6 months thereafter. A negative blood 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 6 months thereafter
  • Exclusion Criteria

    • Known or suspected CNS metastases or active leptomeningeal disease
    • History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of T1-2 prostate cancer Gleason score <6, adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
    • Participated in any other investigational study or received an experimental therapeutic procedure considered to interfere with the study in the 4 preceding weeks of the pre-registration
    • Any chemotherapy treatment in the 4 preceding weeks before pre-registration
    • Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control
    • Severe or uncontrolled cardiovascular disease uncontrolled hypertension (sustained systolic blood pressure > 150 mm Hg and/or diastolic > 100 mm Hg despite antihypertensive therapy)
    • History of cerebrovascular accident or intracranial hemorrhage within 6 months prior to registration
    • Positive HIV test
    • Known history of HTLV-1, HTLV-2, or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment
    • Concomitant diseases that require therapeutic anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon), factor Xa inhibitors (e.g. rivaroxaban, apixaban), direct thrombin inhibitors (e.g. dabigatran) or low molecular weight heparins (LMWH). LMWH is permitted as long as treatment can be withheld for 12 hours prior to subcutaneous implantation
    • Known severe allergy to reagents in the study product (MVX-ONCO-1) such as penicillin, streptomycin
    • Systemic disease other than cancer, that is not controlled by approved medication
    • Patient with active autoimmune disease
    • Chronic immunosuppressive treatment exceeding 20 mg/day of prednisone or an equivalent corticosteroid
      • Note: In acute situation methylprednisone ≤20mg/day or equivalent is allowed during 7 days
    • Women who are pregnant or breast feeding
    • 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:

Inselspital
Freiburgstrasse 8
3010 Bern
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen