Clinical trial NCT02630368 (phase 1/phase 2, status: recruiting)
Conditions: solid tumors, soft-tissue sarcoma, breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: cyclophosphamide and jx-594 dose escalation, cyclophosphamide and jx-594, cyclophosphamide, avelumab and jx-594 and cyclophosphamide
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, ClCCN(CCCl)P1(=O)NCCCO1, ClCCN(CCCl)P1(=O)NCCCO1, NC1=NC(=O)N(C=N1)[C@H]1C[C@H](O)[C@@H](CO)O1
Eligibility criteria:

        Main Inclusion Criteria:

          1. Histology:

               -  Phase Ib : Patient with histologically confirmed solid tumor

               -  Phase II :

                    -  Patients with histologically confirmed HER2 negative breast cancer
                       (treatment by CP+JX-594), or triple negative (treatment by avelumab +
                       CP+JX-594)

                    -  Patients with histologically confirmed soft tissue sarcoma confirmed by the
                       RRePS Network, b)Progressive disease or relapse, after standard therapy
                       according to RECIST v1.1 criteria diagnosed on the basis of two CT scan or
                       MRI obtained at an interval less than 6 months in the period of 12 months
                       prior to inclusion and confirmed by central review

          2. Metastatic or unresectable locally advanced disease

          3. Age ≥ 18 years

          4. ECOG ≤ 1 (Phase Ib), ≤ 2 (Phase II JX+CP) and ≤ 1 (Phase II avelumab+JX+CP).

          5. Life expectancy > 3 months,

          6. Measurable disease according to RECIST v1.1 outside any previously irradiated field.
             For patients treated by avelumab+JX+CP, at least one injectable site ≥ 2 cm and ≤ 8 cm
             in diameter and one distant non-injected measurable site (target site)

          7. At least three weeks since last chemotherapy, immunotherapy or any other
             pharmacological treatment and/or radiotherapy.

          8. Adequate hematological, renal, metabolic and hepatic functions.

          9. Women of childbearing potential must have a negative serum pregnancy test before study
             entry. Both women and men must agree to use a medically acceptable method of
             contraception throughout the treatment period and for six months after discontinuation
             of treatment.

         10. Patients informed of risks regarding drug interactions: patients receiving any
             substances that are inhibitors or inducers of CYP450 2B6 are ineligible

         11. Voluntarily signed and dated written informed consent prior to any study specific
             procedure.

         12. Patients with a social security in compliance with the French law.

        Main Exclusion Criteria:

          1. Previous treatment with JX-594 or other vaccina vector based treatment or with
             PD1/PDL1 antagonist for treatment by avelumab.

          2. Concomitant diseases/conditions (non exhaustive list):

               1. Clinically significant immunodeficiency, such as HIV or active Hepatite B or C

               2. Any other major illness that, in the Investigator's judgment, will substantially
                  increase the risk associated with the patient's participation in this study.

               3. History of severe exfoliative skins condition requiring systemic treatment for
                  more than 4 weeks in the last two years.

               4. active autoimmune disease for patients treated by avelumab

          3. Active central nervous system metastasis (CNS)

          4. Participation to a study involving a medical or therapeutic intervention in the last
             30 days.

          5. Previous enrolment in the present study.

          6. Patient unable to follow and comply with the study procedures because of any
             geographical, social or psychological reasons.

          7. Known hypersensitivity to any involved study drug or any of its formulation
             components.

          8. Use of steroids (any route of administration), interferon/pegylated interferon or
             ribavirin that cannot be discontinued within 14 days prior to any JX-594 dose.

          9. No prior malignancy except for the following: adequately treated basal or squamous
             cell skin cancer, in situ cervical cancer, adequately treated Stage 1 or Stage 2
             cancer from which the patient is currently in complete remission or any other cancer
             from which the patient has been disease-free for 3 years.

         10. Active cardiovascular disease, including but not limited to significant coronary
             artery disease (e.g. requiring angioplasty or stenting) or congestive heart failure
             within the preceding 12 months. (treatment by CP+JX)

         11. Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to
             and 48 hours after all JX-594 treatments.

         12. Pulse oximetry O2 saturation < 90% at rest on room air.

         13. Experienced a severe systemic reaction or side-effect as result of previous smallpox
             vaccination.

         14. Cardiac disease: LVEF out of normal limits ; cumulative dose of anthracyclines in
             excess of 450 mg/m²

         15. Known urinary tract obstruction

         16. Household contact exclusions for patients enrolled: children< 1 year old ; People with
             skin disease (e.g., eczema, atopic dermatitis and related diseases…),
             Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including
             AIDS, organ transplant recipients, hematologic malignancies)

         17. Vaccination within 4 weeks of the first dose of study treatment and while on trial is
             prohibited except for administration of inactivated vaccines.