Trial Title:
ABC-lung: Atezolizumab, Bevacizumab and Chemotherapy in EGFR-mutant Non-small Cell Lung Carcinoma
NCT ID:
NCT04245085
Condition:
EGFRmutant Stage IIIB/C or IV Non-squamous NSCLC
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Bevacizumab
Carboplatin
Pemetrexed
Atezolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Patients in both treatment arms will receive atezolizumab at a fixed dose of 1200 mg i.v.
on day one of every 3-week (3 days) cycle, until progression of disease determined
according to RECIST v1.1 or lack of tolerability, or patient declines further treatment.
Treatment beyond RECIST-defined progression will be allowed if patient is continuing to
derive clinical benefit.
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Tecentriq
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Patients in both treatment arms will receive bevacizumab at a dose of 15 mg/kg i.v. on
day one of every 3-week (+/- 3 days) cycle, until progression of disease determined
according to RECIST v1.1 or lack of tolerability, or patient declines further treatment.
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Avastin
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Patients in treatment Arm A will receive carboplatin, AUC5 every 3 weeks for 4-6 cycles.
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Patients in treatment Arm A will receive paclitaxel, 175-200 mg/m2 (at the investigators'
discretion), every 3 weeks for 4-6 cycles.
Arm group label:
Arm A
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Patients in treatment Arm B will receive Pemetrexed, 500 mg/m2 every 3 weeks until
progression of disease determined according to RECIST v1.1 or lack of tolerability, or
patient declines further treatment.
Arm group label:
Arm B
Other name:
Alimta
Summary:
ETOP 15-19 ABC-lung is an international, multi-centre open-label, randomized phase II
trial with two non-comparative parallel arms of atezolizumab plus bevacizumab with
carboplatin-paclitaxel (Arm A) or atezolizumab, bevacizumab and pemetrexed (Arm B) in
patients with stage IIIB-IV non-squamous non-small cell lung cancer (NSCLC) harbouring
EGFR mutations after failure of standard EGFR tyrosine kinase inhibitors (TKIs).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients (male/female) must be ≥18 years of age.
2. Chemotherapy naïve, non-squamous NSCLC, stage IIIB/C (not amenable to radical
therapy) or IV. Patients who have received previous adjuvant or neoadjuvant
chemotherapy are eligible if the date of last dose of treatment was at least 12
months before randomisation.
3. Known EGFR mutations genotypes by tissue or ctDNA, patients with common mutations
(L858R or Del19) and other rare mutations (e.g. S768I, G719X) are eligible.
4. Measurable or evaluable disease by RECIST v1.1.
5. Disease progression (during or after) or unacceptable side effects from prior
treatment with at least one EGFR TKI (washout period = 7 days).
If most recent line of treatment (1st or 2nd line) was a third-generation EGFR TKI
(e.g. osimertinib):
- Patient must be known to be EGFR mutation positive, either on fresh tumour
biopsy taken >7 days prior to protocol treatment start or by recent ctDNA
analysis (informative ctDNA test, local test).
- T790M genotype is allowed
If most recent line of treatment (1st or 2nd line) was a first- or second-generation
EGFR TKI (e.g. afatinib, dacomitinib, erlotinib, gefitinib):
- Patient must be known to be tissue EGFR T790M wild type (local test) on most
recent line of EGFR TKI or if no tissue re-biopsy, no evidence of T790M on
ctDNA but identified L858R, del19, S768I or G719X genotypes (informative ctDNA
test, local test)
6. Treatment with an EGFR TKI therapy for at least 30 days
7. Adequate haematological function:
- Haemoglobin greater or equal 90 g/L
- Absolute neutrophils count (ANC) greater or equal 1.5× 109/L
- Platelet count greater or equal 100× 109/L
8. Adequate renal function:
• Creatinine clearance greater or equal 45 mL/min (using the Cockcroft-Gault
formula)
9. Adequate liver function:
- ALT and AST less or equal 2.5× ULN. If the patient has liver metastases, ALT
and AST must be less or equal 5× ULN
- Total bilirubin less or equal 1.5x ULN.
10. Willingness to provide any surplus tumour sample obtained at the time of acquired
resistance to prior EGFR TKI
11. Men and women of childbearing potential must agree to use adequate contraception
12. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
13. Life expectancy greater or equal 12 weeks
14. Women of childbearing potential, including women who had their last menstrual period
in the last 2 years, must have a negative serum or urine pregnancy test within 7
days before randomisation.
15. Patient is willing and able to comply with the protocol for the duration of the
trial including undergoing treatment and scheduled visits and examinations including
follow up.
Exclusion Criteria:
1. Prior systemic cytotoxic chemotherapy for advanced stage NSCLC Patients who had
received previous adjuvant or neoadjuvant chemotherapy are eligible if the last dose
of treatment was at least 12 months before randomisation.
2. Prior therapy with bevacizumab or other anti-angiogenic agent
3. Prior immune checkpoint inhibitor therapy
4. More than two lines of EGFR TKI therapy
5. Known small-cell lung carcinoma (SCLC) or high grade neuroendocrine carcinoma (if
progression biopsy has been performed locally).
6. Squamous cell histologic subtype
7. Known EGFR T790M positive genotype by tissue on most recent EGFR TKI progression or
ctDNA and have not received an approved EGFR TKI targeting T790M (e.g. a
third-generation EGFR TKI such as osimertinib).
8. Active or untreated CNS metastases as determined by brain MRI
- Patients with CNS metastases must be non-progressive by RECIST v1.1 and
symptomatically stable with no ongoing requirement for corticosteroids as
therapy for CNS disease; anticonvulsants at a stable dose allowed
9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of
radiation within 4 weeks of randomization.
10. Presence or history of a malignant disease that has been diagnosed and/or required
therapy within the past 3 years. Exceptions to this exclusion include the following:
completely resected basal cell and squamous cell skin cancers, and completely
resected carcinoma in situ of any type.
11. Clear tumour infiltration into the thoracic great vessels (seen on imaging)
12. QTc of grade ≥3 according to CTCAE v5.0
13. Active autoimmune disease that has required systemic treatment in past 2 years.
Patients with vitiligo, controlled type I diabetes mellitus on stable insulin, or
residual autoimmune-related hypothyroidism only requiring hormone replacement or
psoriasis not requiring systemic treatment are permitted
14. Active or uncontrolled HIV, tuberculosis, hepatitis B or C infection
15. Live attenuated vaccination within 4 weeks prior to randomisation.
16. Subject receiving any biologic drugs targeting the immune system (for example, TNF
blockers, anakinra, rituximab, abatacept, or tocilizumab) within 6 weeks prior to
treatment start.
17. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography scan. History of radiation pneumonitis in the radiation
field (fibrosis) is permitted
18. Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg
and/or diastolic blood pressure >100 mmHg)
- Anti-hypertensive therapy to achieve these parameters is allowable.
19. Prior history of hypertensive crisis or hypertensive encephalopathy
20. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis) within 6 months prior to randomization
21. History of haemoptysis (greater or equal 2.5mL of bright red blood per episode)
within 1 month prior to randomization
22. Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
anticoagulation)
23. Current or recent (within 10 days before randomization) use of aspirin (>325 mg/day)
or treatment with dipyramidole, ticlopidine, clopidogrel, and clostazol
24. Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents
for therapeutic purposes that has not been stable for >2 weeks prior to
randomization
- The use of full-dose oral or parenteral anticoagulants is permitted as long as
the INR or aPTT is within therapeutic limits (according to the medical standard
of the enrolling institution) and the patient has been on a stable dose of
anticoagulants for at least 2 weeks prior to randomization.
- Prophylactic anticoagulation for the patency of venous access devices is
allowed, provided the activity of the agent results in an INR <1.5× ULN and
aPTT is within normal limits within 14 days prior to randomization.
- Prophylactic use of low-molecular-weight heparin (i.e., enoxaparin 40 mg/day)
is permitted.
25. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to the first dose of bevacizumab
- Major surgery or significant traumatic injury 28 days prior to the first dose
of bevacizumab.
- Minor surgical procedure within 7 days, or placement of a vascular access
device 2 days prior to the first dose of bevacizumab.
26. History of abdominal or tracheoesophageal fistula or gastrointestinal perforation
within 6 months prior to randomization
27. Clinical signs of gastrointestinal obstruction or requirement for routine parenteral
hydration, parenteral nutrition, or tube feeding
28. Evidence of abdominal free air not explained by paracentesis or recent surgical
procedure
29. Serious, non-healing wound, active ulcer, or untreated bone fracture
30. Proteinuria, as demonstrated by urine dipstick or >1.0 g of protein in a 24-hour
urine collection
- All patients with greater or equal 2+ protein on dipstick urine analysis at
baseline must undergo a 24 hour urine collection and must demonstrate lesser or
equal 1 g of protein in 24 hours.
31. Any unresolved toxicities from prior therapy greater than CTCAE v5.0 grade 1 at the
time of starting trial treatment with the exception of alopecia
32. History of hypersensitivity to the known active substances (atezolizumab,
bevacizumab and chemotherapy drugs) or to any of the excipients.
33. History of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other
recombinant human or humanised antibodies.
34. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
35. Women who are pregnant or in the period of lactation.
36. Sexually active men and women of childbearing potential who are not willing to use
an effective contraceptive method during the trial and up to 6 months after
discontinuing trial treatment
37. History of active diverticulitis
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
LungenClinic Grosshansdorf
Address:
City:
Großhansdorf
Country:
Germany
Facility:
Name:
Asklepios Fachkliniken München-Gauting
Address:
City:
München
Country:
Germany
Facility:
Name:
National Cancer Center
Address:
City:
Goyang
Country:
Korea, Republic of
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Country:
Korea, Republic of
Facility:
Name:
National University Hospital
Address:
City:
Singapore
Country:
Singapore
Facility:
Name:
ICO - Hospital Universitari Germans Trias i Pujol
Address:
City:
Badalona
Country:
Spain
Facility:
Name:
Hospital De La Santa Creu I Sant Pau
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Vall d'Hebron University Hospital
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
OSI Bilbao Basurto
Address:
City:
Bilbao
Country:
Spain
Facility:
Name:
Complejo Hospitalario de Jaén
Address:
City:
Jaén
Country:
Spain
Facility:
Name:
Hospital Teresa Herrera
Address:
City:
La Coruña
Country:
Spain
Facility:
Name:
Hospital Universitario Insular Gran Canaria
Address:
City:
Las Palmas De Gran Canaria
Country:
Spain
Facility:
Name:
Hospital Puerta de Hierro
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
Hospital Universitario Fundacion Jimenez Díaz
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
Hospital General de Valencia
Address:
City:
Valencia
Country:
Spain
Facility:
Name:
Hôpitaux Universitaires de Genève
Address:
City:
Geneva
Country:
Switzerland
Facility:
Name:
Kantonsspital St. Gallen
Address:
City:
St. Gallen
Country:
Switzerland
Facility:
Name:
UniversitätsSpital Zürich
Address:
City:
Zürich
Country:
Switzerland
Start date:
September 29, 2020
Completion date:
December 2024
Lead sponsor:
Agency:
ETOP IBCSG Partners Foundation
Agency class:
Other
Collaborator:
Agency:
Roche Pharma AG
Agency class:
Industry
Source:
ETOP IBCSG Partners Foundation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT04245085
