A Study to Find Out How Effective and Safe Different Treatments are in Patients Who Have a Type of Lung Cancer (Known as Non-Small Cell Lung Cancer [Stage III])
- Conditions
- on-Small Cell Lung Cancer (NSCLC)MedDRA version: 23.1Level: LLTClassification code 10084713Term: TumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-004149-19-IT
- Lead Sponsor
- F. HOFFMANN - LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 320
Age >=18 years
Body weight >=30 kgWhole-body positron emission tomography/computed tomography scan (PET/CT) performed prior and within 42 days of the first dose of cCRT or sCRT
Histologically or cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology (Version 8, American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system (Amin et al. 2017).
Prior receipt of at least two prior cycles of platinum-based chemotherapy given concurrently with radiotherapy (cCRT); or at least two prior cycles of platinum-based chemotherapy given prior to radiotherapy (sCRT)
The RT component in the cCRT or sCRT must have been at a total dose of radiation of 60 (± 10%) Gy (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or three dimension (3D)-conforming technique
No disease progression during or following platinum-based cCRT or sCRT
Life expectancy = 12 weeks
Documented tumor PD-L1 status
Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
Adequate hematologic and end-organ function
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, during the treatment period and for at least 90 days after the final dose of alectinib or durvalumab (Cohort A1 only)
For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, during the treatment period, and for at least 35 days after the final dose of entrectinib, or 90 days after the final dose of durvalumab (Cohort A2 only)
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, during the treatment period, and for at least 14 days after the final dose of pralsetinib, or at least 90 days after the final dose of durvalumab (Cohort A3 only)
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm during the treatment period and for least 90 days after the final dose of alectinib or durvalumab (Cohort A1 only)
For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom plus an additional contraception method, and agreement to refrain from donating sperms, during the treatment period and for at least 3 months after the final dose of entrectinib or final dose of durvalumab Cohort A2 only)
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, during the treatment period and for at least 7 days after the final dose of pralsetinib and at least 90 days after the final dose of durvalumab (Cohort A3 only)
Ability to swallow entrectinib intact, without chewing, crushing, or opening the capsules (Cohort A2 only)
Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen
Documented ALK fusion positivity (Cohort A1 only)
Documented ROS1 fusion positivity (Cohort A2 only)
Documented RET fusion positivity (Cohort A3 only
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 160
F.1.3 Elderly (>=65 yea
Any history of previous NSCLC and/or any history of prior treatment for NSCLC
Any evidence of Stage IV disease
If pleural effusion is present the following criteria must be met to exclude malignant involvement (T4 disease):
When pleural fluid is visible on both the computed tomography scan and chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative.
Patients with exudative pleural effusions are excluded regardless of cytology.
Patients with effusions that are minimal (i.e., not visible on chest X-ray) that are too small to safely tap are eligible
NSCLC known to have one or more of the following ALK point mutations, as identified by site local testing or Sponsor central testing: I1171X (where X is any other amino acid), V1180L, G1202R (Cohort A1).
NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing
Liver disease
Positive hepatitis B surface antigen test at screening
Patients known to be positive for hepatitis C virus antibody
HIV infection, patients are excluded if HIV is not adequately controlled (specific criteria apply).
Known active tuberculosis
Presence of clinically symptomatic interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis
Grade = 2 pneumonitis from prior cCRT or sCRT
Symptomatic bradycardia (Cohort A1,A2)
Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
Left ventricular ejection fraction less than or equal to 50% observed during the screening for the study (Cohort A2)
Any gastrointestinal (GI) disorder that may affect absorption of oral medications
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest CT scan
History of malignancy other than NSCLC within 5 years prior to screening
Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer
Major surgical procedure, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Treatment with systemic immunostimulatory agents
Treatment with live, attenuated vaccine
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Treatment with systemic immunosuppressive medication
Prior treatment with ALK inhibitors (Cohort A1)
Prior treatment with ROS1 inhibitors (Cohort A2)
Prior treatment with RET inhibitors (Cohort A3)
Prior treatment with CD137 agonists or immune checkpoint blockade therapies
Prior allogeneic stem cell or solid organ transplantation
History of hypersensitivity to alectinib, durvalumab, or any of their excipients (Cohort A1)
History of hypersensitivity to
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method