Thoracic Radiotherapy plus Durvalumab in Elderly and/or frail NSCLC stage III patients unfit for chemotherapy- Employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy

Phase 1

Active, not recruiting

• Conditions: unresectable stage III NSCLC (Non–small-cell lung cancer); MedDRA version: 21.1Level: PTClassification code 10029519Term: Non-small cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029520Term: Non-small cell lung cancer stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10025052Term: Lung cancer non-small cell stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10025054Term: Lung cancer non-small cell stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10025053Term: Lung cancer non-small cell stage IIIASystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-002192-33-DE
• Lead Sponsor: Frankfurter Institut für Klinische Krebsforschung IKF GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-10-24
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

1.Fully-informed written consent and locally required authorization (European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2.Age = 18 years.
3.Histologically documented diagnosis of unresectable stage III NSCLC.
4.Non-feasibility of sequential chemo-/radiotherapy as determined by the site’s multi-disciplinary tumor board; If there is no tumor board, then this decision will be made by the investigator in consultation with a radiation oncologist, if the investigator is not a radiation oncologist; or by the investigator in consultation with an oncologist, if the investigator is not an oncologist.
5.Fulfills at least one of the following criteria:
•Performance status (PS) 2 (ECOG scale)
•ECOG 1 and CCI = 1
•Age = 70 years
6.Must have a life expectancy of at least 12 weeks.
7.FEV1 = 40% (Best/Soll)
8.DLCO or DLCO/VA (Hb-corrected, if available) = 40% (Best/Soll)
9.FVC or VC = 70% (Best/Soll)
10.At least one measurable site of disease as defined by RECIST 1.1 criteria.
11.Adequate bone marrow and renal function including the following:
oHemoglobin = 9.0 g/dL;
oabsolute neutrophil count = 1.0 x 10^9/L;
oplatelets =75x 10^9/L;
oCalculated creatinine clearance =30 mL/min as determined by the Cockcroft-Gault equation
12.Adequate hepatic function (with stenting for any obstruction, if required) including the following:
o Serum bilirubin = 1.5 x institutional upper limit of normal (ULN);
oAST (SGOT) / ALT (SGPT) = 2.5x institutional ULN
13.Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
14.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:
oWomen <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).
oWomen =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).
15.The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
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 19
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 38

Exclusion Criteria

1.Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study, or during the follow-up period of an interventional study.
2.Participation in another clinical study with an investigational product within 21 days prior to the first dose of the study treatment.
3.Prior immunotherapy or use of other investigational agents, including anti-PD-1, anti-PD-L1, including durvalumab, anti-PD-L2, or anti-CTLA-4 antibody, therapeutic cancer vaccines.
4.History or current radiology suggestive of interstitial lung disease.
5.Oxygen-dependent medical condition.
6.Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is acceptable.
7.Prior thoracic radiotherapy within the past 5 years before the first dose of study drug.
8.Major surgery within 4 weeks prior to enrollment into the study; patients must have recovered from effects of any major surgery.
9.Active or prior documented autoimmune or inflammatory disorders (except inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease]; (including diverticulitis [with the exception of diverticulosis], celiac disease, systemic lupus erythematosus, Sarcoidosis, or Wegener’s syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis). The following are exceptions to this criterion: Patients with vitiligo or alopecia, Patients with hypothyroidism (e.g., following Hashimoto’s disease) 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
10.Active, uncontrolled inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease]. Patients in stable remission for more than 1 year may be included.
11.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, interstitial lung disease, gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
12.History of another primary malignancy except for: Malignancy treated with curative intent and with no known active disease = 3 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
13.History of leptomeningeal carcinomatosis
14.History of active primary immunodeficiency
15.History of allogenic organ or tissue transplantation.
16.Clinical diagnosis of active tuberculosis.
17.Positive testing for HBV sAg or HCV RNA indicating acute or chronic infection. Patients with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
18.Positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
1

Study & Design

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