Phase II trial evaluating the efficacy of durvalumab (MEDI4736) as second-line therapy in Non- Small-Cell Lung Cancer patients receiving concomitant steroids

Phase 1

• Conditions: on- Small-Cell Lung Cancer; MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10025122Term: Lung squamous cell carcinoma stage ISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003645-41-IT
• Lead Sponsor: FONDAZIONE RICERCA TRASLAZIONALE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 12 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

1.Adequate normal organ and marrow function as definedbelow:
-Haemoglobin = 9.0g/dL
-Absolute neutrophil count (ANC)1.0 x109/L
-Platelet count = 100 x 109/L
-Serum bilirubin = 1.5 x institutional upper limit of normal(ULN).
-AST (SGOT)/ALT (SGPT) =2.5 x institution a lupper limit of normal unless liver metastases are present, in which case it must be =5xULN
-Measured creatinine clearance (CL)> 40mL/minor Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24- hour urine collection for determination of creatinine clearance:
Males:
CreatinineCL (mL/min)=Weight(kg)x(140–Age) 72 x serum creatinine (mg/dL)

Females:
CreatinineCL (mL/min)=Weight (kg) x (140–Age)x0.85
72 x serum creatinine (mg/dL)

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. Women who are surgically sterile (ie, bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) are eligible. The following age specific requirments 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 orhysterectomy).
- 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 hormonaltreatments,hadradiation-inducedmenopausewithlastmenses>1year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy orhysterectomy).
3.Histological or cytological confirmed diagnosis of advanced or metastatic NSCLC with no evidence of EGFR mutations or ALK rearrangement.
4.Previous platinum-based chemotherapy. Only one line of previous chemotherapy is allowed. Adjuvant or neoadjuvant chemotherapy is not considered a line of therapy if completed at least 6 months before trial inclusion
5.Age > 18 years at time of studyentry.
6.Performance Status 0-1(ECOG)
7.Body weight>30kg
8.Able of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
9.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.
10.Must have a life expectancy of at least 12weeks
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

Exclusion Criteria

1.Participation in another clinical study with an investigational product
2.Concurrent enrolment in another clinical study
3.Any previous treatment with a checkpoint inhibitor
4.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 study drug and of low potential risk for recurrence
•Adequately treated non-melanoma skin cancer or lentigomaligna without evidence ofdisease
•Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer insitu.
5.Receipt of the last dose of anticancer therapy 21 days prior to the first dose of study drug
6.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions:
- Intranasal, inhaled, topical steroids, or local steroid injections
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions
7.Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy
- Patients with Grade =2 neuropathy will be evaluate donacase-by-case basis after consultation with the StudyPhysician.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
8.Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
9.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
10.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.
11.History of allogenic organt ransplantation.
12.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Patients with vitiligo oralopecia
- Patients with hypothyroidism stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
13.Uncontrolled intercurrent illness
14.History of leptomeningeal carcinomatosis
15.History of active primary immune deficiency
16.Active infection including tuberculosis,hepatitis B, hepatitis C,or human immunodeficiency virus.
17.Receipt of live attenuated vaccine within 30 days prior to the first dose of IP
18.Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
19.Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
20.Prior randomisation or treatment in a previous durvalumab clinical study re

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified