FRAIL-IMMUNE (GORTEC 2018-03) - Combination of Durvalumab With Carboplatin/Paclitaxel

Korábbi kezelés

• History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• Patient whom disease progressed within 6 months after the start date of the previous chemotherapy (faster progressors)
• Symptomatic or active leptomeningial or parenchymal brain metastases. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment ot the brain metastases; these Imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of <=10mg/day of prednisone or its equivalent and anticonvulsant for at least 14 days prior to the start of treatment.
• Current or prior use, or need for the following concomitant medications/interventions not permitted during the study treatment period :
  • Any concurrent chemotherapy or radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug (except palliative radiotherapy on a non-target lesion after discussion with the coordinating investigator), immunotherapy, biologic or hormonal therapy for cancer treatment, other than any stated in the protocol (Note: concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable)).
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab including, but not limited to systemic corticosteroids at doses exceeding 10 mg/day of prednisone or equivalent, methotrexate, azathioprine, and TNF-α blockers. Use of immunosuppressive medications for the management of investigational product-related AEs or in subjects with contrast allergies is acceptable.
  • Phenytoin given in a prophylactic intent
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP (Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP).
  • Strong inhibitors and inducers of CYP3A4
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• Participation in another clinical study with an investigational product during the last 28 days prior to first study drug administration

Más betegség

• Patient whom tumor lesion is hemorrhagic or at risk of bleeding

Laborértékek

• Prior anticancer therapy in metastatic or recurrent setting In case patient received neoadjuvant or adjuvant anti-cancer treatment, it must have been completed for at least 6 months prior to study drugs initiation and patient must have no unresolved toxicity NCI CTCAE Grade ≥2 with the exception of alopecia, vitiligo and laboratory values defined as inclusion criteria.
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the coordinating investigator.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the coordinating investigator.
• Active or prior/history of disease/medical condition listed below:
  • Inflammatory or interstitial lung disease
  • Documented autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., Crohn's disease, ulcerative colitis], systemic lupus erythematosus, sarcoidosis syndrome or Wegener syndrome, granulomatosis with polyangitis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 2 years except for autoimmune hypothyroidism on a stable dose of thyroid supplementation and patients with type 1 diabetes mellitus on a stable dose of insulin.
  • Note: Subjects with alopecia, vitiligo, psoriasis not requiring systemic treatment (within the past 2 years) or chronic skin condition that does not require systemic therapy, are not excluded, as well as patients without active disease in the last 5 years (after consultation with the study physician) and patients with celiac disease controlled by diet alone.
  • Mean QT interval corrected for heart rate (QTc) ≥470 ms using Fredericia's Correction.
  • Clinically significant cardiac disease or congestive heart failure > New York Heart Association (NYHA) class 2. Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
  • History of primary immunodeficiency
  • Allogeneic organ transplantation
  • Documented hypersensitivity to the active substance or excipient of the study drugs
  • Any uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Active peptic ulcer disease or gastritis,
  • Active bleeding diatheses including any subject known to have evidence of acute risk,
  • Serious chronic gastrointestinal conditions associated with diarrhea
  • Any psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent
• Pregnant or breastfeeding women (Women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to study treatment start. A positive urine test must be confirmed by a serum pregnancy test).

• Age ≥ 18 years at the time of study entry;
• Histological or cytological confirmation of the diagnosis of Squamous Cell Carcinoma of the Head and Neck;
• Primary tumor located in one of the following : oral cavity, larynx, oropharynx or hypopharynx (NB: sinuses and nasopharynx locations are not allowed; isolated cervical lymphnodes with unknown primary site may be discussed with the coordinating investigator on a case by case basis)
• Archival tumor sample available at the time of inclusion with sufficient material to achieve the translational research program. Archival material must have been collected 3 months before inclusion at the latest, unless a new tumor sample must be collected.
• Disease must be in metastatic (Stage IVc) or recurrent setting;
• Documented progression of measurable disease as per the RECIST 1.1 (NB: in case of a single metastatic lesion, the tumor size must be > 20mm to allow tumor biopsy)
• Patients must be ineligible to standard therapies, including cisplatin. Ineligibility is defined as at least one of the following criteria:
  • Creatinine clearance (CrCl) : 40 < CrCl < 60ml/min
  • Any severe comorbidity rendering the patient ineligible to standard chemotherapy, as per investigator's judgment.
• Eastern Cooperative Oncology Group performance status of 0, 1 or 2
• Must have a life expectancy of at least 12 weeks
• Body weight > 30Kg;
• Adequate organ and marrow function as defined below:
  • Hemoglobin ≥ 9.0 g/dl
  • Absolute Neutrophils Count (ANC) ≥ 1.5 x 109/L
  • Platelet count ≥ 100 x 109/L
  • Creatinine clearance ≥ 40 ml/min using the following appropriate formulae:
  • Cockroft-Gault formula for female : 0.85 x weight (Kg) x (140-age) / 72 x serum creatinine (mg/dL)
  • Cockroft-Gault formula for male : weight (Kg) x (140-age) / 72 x serum creatinine (mg/dL)
  • MDRD for patients older than 65 years: 186.3 x (serum creatinine (µmol/L / 88.4) -1.154 x Age -0.203 x (0.742 if female) x (1.212 if black patient [African origin]).
  • AST/ALT ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 x ULN
  • Serum total bilirubin ≤ 1.5 x ULN (in the absence of Gilbert's syndrome)
  • Coagulation panel : INR or PT ≤ 1.5 x ULN
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
• Patient (male or female) using a highly effective contraception as defined in appendix 9 during the study treatment period and until 6 months after the last administration of carboplatin and/or paclitaxel or until 90 days after the last administration of durvalumab, whichever is longer. Prior to dispensing study drugs, the investigator must confirm and document the patient's (and his/her partner) use of highly effective contraceptive methods, dates of negative pregnancy tests, and confirm the patient's understanding of the teratogenic potential of study drugs.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Covered by a medical insurance.
• Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment