2024-510712-75-00
Recruiting
Phase 1/2
COTESARC : A multicentre, open-label, Phase I-II study evaluating the combination of a MEK inhibitor and a PDL1 inhibitor in pediatric and adult patients with locally advanced and/or metastatic soft tissue sarcoma
Overview
- Phase
- Phase 1/2
- Status
- Recruiting
- Sponsor
- Centre Leon Berard
- Enrollment
- 80
- Locations
- 5
- Primary Endpoint
- Safety run in Incidence of severe toxicities (ST) during the 1st cycle of treatment
Overview
Brief Summary
Safety run in To confirm the safety of cobimetinib when combined with atezolizumab in pediatric STS patients (≥6 months to <12 years). Phase II part To assess the clinical activity of cobimetinib combined with atezolizumab in 4 independent and parallel cohorts (20 patients in each cohorts) based on histological types: Rhabdomyosarcoma (RMS), Malign Peripheral Nerve Sheath Tumors (MPNST), Complex genomics sarcomas: Single genomic sarcoma.
Eligibility Criteria
- Ages
- 0 years to 65+ years (65+ Years, 18-64 Years, 0-17 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female patients aged of at least : 12 years on day of signing informed consent.
- •Performance status: oKarnofsky performance status for pediatric patients ≥12 years of age ≥ 70%; oPS ECOG for adult patients: 0 or
- •Life expectancy of at least 16 weeks
- •Demonstrate adequate organ function based on screening laboratory tests performed within 7 days prior C1D
- •Absolute neutrophil count (≥1.5 109 /L) *Platelets (≥100 109 /L) *Hemoglobin (≥9 g/dL (without transfusion within 7 days)) *Serum creatinine OR Creatinine clearance according to CKD-EPI for adults or C-KID formula for pediatric patients (≤1.5 X ULN) OR ≥ 30 mL/min/1.73m2 for patient with creatinine levels > 1.5 ULN) *Serum total bilirubin (≤ 1.5 X ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤ 3 x ULN is acceptable) OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 ULN) *ASAT and ALAT and ALP (≤ 3 X ULN (or up to 5ULN in case of liver metastasis or hepatic infiltration) *INR and Activated Partial Thromboplastin Time (aPTT) (≤1.5 X ULN Note: Patients receiving therapeutic anticoagulation must be on stable dose) *Troponin T or I (Negative (< ULN))
- •Resolution (i.e. ≤ Grade 1 with the exception of alopecia all grades and Grade 2 for neuropathy, lab values presented in criteria I12.) of any toxicities related to previous anti-cancer treatment.
- •Women patient of child-bearing potential must have a negative serum pregnancy test before C1D1 and must agree to use effective forms of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drugs.
- •Sexually active and fertile men must agree to use contraceptive measures up to 5 months after the last study drugs.
- •Written informed consent from patient, parents if applicable/legal representative, before any study-specific screening procedures, and willingness to comply to study visits and procedures.
- •Patients must be covered by a medical insurance.
Exclusion Criteria
- •Soft tissue sarcoma disease considered curable with surgery or radiotherapy.
- •Patients using, or requirement to use while on the study, or not respecting the minimal wash-ouions or significant abdominal traumatic injury (Minimal wash out period before C1D1: 60 days) *Live vaccines. Note - Influenza vaccination should be given durint period of medications listed below : *Any approved anti-cancer systemic treatment including chemotherapy, hormonotherapy, biological therapy, or immunotherapy (Minimal wash out period before C1D1: 2 weeks) *Any investigational agents (Minimal wash out period before C1D1: 4 weeks) *Radiotherapy Note: palliative radiotherapy on non-target lesions is allowed (Minimal wash out period before C1D1: 3 weeks) *Surgery ▪ Major surgical procedure, open biopsy, or significant traumatic injury (Minimal wash out period before C1D1: 4 weeks) *Surgery Abdominal surgery, abdominal interventg influenza season. Patients must not receive live attenuated influenza vaccine (e.g., FluMist®) (Minimal wash out period before C1D1: 4 weeks); *Systemic immunostimulatory agents, including but not limited to IFN-α, IFN-γ, or IL-2 (Minimal wash out period before C1D1: 4 weeks) *Immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) with the exceptions of intranasal, inhaled, or topical corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day (or 0.1 mg/kg in pediatric patients) of prednisone, or an equivalent corticosteroid (Minimal wash pout period before C1D1: 2 weeks) *P-gp inhibitors, Strong or moderate inhibitors of CYP3A4 and Strong CYP3A4 inducers (Non minial wash-out periode before C1D1) *Oral or IV antibiotics Note: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection, pneumocystis or chronic obstructive pulmonary disease exacerbation) are eligible (minimal wash out period before C1D1 2 weeks)
- •Patients with a malignancy other than STS within 5 years prior to C1D1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated in situ carcinoma of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal in situ carcinoma treated surgically with curative intent).
- •History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 17.3 for a more comprehensive list of pre-existing autoimmune diseases and immune deficiencies) with the following exceptions – listed in the protocol.
- •Patients with HIV, active B or C hepatitis infection or any other active infection.
- •Patients with active tuberculosis.
- •Prior allogeneic bone marrow transplantation or solid organ transplant for another malignancy in the past.
- •History of idiopathic pulmonary fibrosis (including pneumonitis), druginduced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan.
- •Patients with a high-risk of hemorrhage or history of coagulopathy
- •Pregnant or breastfeeding women.
Outcomes
Primary Outcomes
Safety run in Incidence of severe toxicities (ST) during the 1st cycle of treatment
Safety run in Incidence of severe toxicities (ST) during the 1st cycle of treatment
Phase II part Progression Free rate after 16 weeks of treatment (PFR16w)
Phase II part Progression Free rate after 16 weeks of treatment (PFR16w)
Secondary Outcomes
- Nature, frequency and severity of AE according to NCI-CTCAE V5.0
- ORR at 8 and 16 weeks according to RECIST V1.1 and iRECIST Duration of response; PFS; OS
Investigators
Nadège CORRADINI
Scientific
Centre Leon Berard
Study Sites (5)
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