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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-002029-12 | EudraCT Number | ||
| ESR-15-11666 | Other Identifier | AstraZeneca | |
| MO39447 | Other Identifier | Roche |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
| Hoffmann-La Roche | INDUSTRY |
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BOOSTER is a randomised, controlled, phase II trial comparing osimertinib and bevacizumab versus osimertinib alone as second-line treatment in patients with stage IIIb-IVb non-small cell lung carcinoma (NSCLC) harbouring activating EGFR (exon 19 deletion or L858R) and T790M resistance mutation.
Lung cancer has been the most common carcinoma in the world for several decades. Non-small cell lung carcinoma (NSCLC) represents approximately 80-85% of all lung cancers. At the time of diagnosis approximately 70% of NSCLC patients already have advanced or metastatic disease not amenable to surgical resection. A significant percentage of early stage NSCLC patients who have undergone surgery subsequently develop distant recurrence.
First-generation EGFR tyrosine kinase inhibitors (TKIs) provide significant clinical benefit in patients with advanced EGFR-mutant (EGFRm) non-small cell lung carcinoma (NSCLC). However, all patients ultimately develop disease progression, driven - as the most prevalent identified biological mechanism - by the acquisition of a second T790M EGFR TKI resistance mutation.
Osimertinib (AZD9291) is a novel oral, potent, and selective third-generation irreversible inhibitor of both EGFRm-sensitizing and T790M resistance mutants. This mono-anilino-pyrimidine compound is structurally distinct from other third-generation EGFR TKIs and offers a pharmacologically differentiated profile from earlier first and second generation EGFR TKIs.
Osimertinib is being evaluated in several prospective clinical trials, notably in frontline treatment, in the adjuvant setting, and in combination with later lines in EGFRm positive advanced disease. Combination treatments that target both tumour cells and tumour microenvironment (such as angiogenesis) may be a promising strategy for further improving efficacy outcomes in patients with EGFRm NSCLC following progression on EGFR TKI therapy and other lines of therapy. There is thus a considerable unmet clinical need for novel therapeutic options that can further extend the efficacy of targeted agents such as EGFR TKIs, across all lines of therapy.
Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the interaction of VEGF-A to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis. Neutralising the biological activity of VEGF regresses the vascularisation of tumours, normalises remaining tumour vasculature, and inhibits the formation of new tumour vasculature, thereby inhibiting tumour growth. Bevacizumab is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC in combination with carboplatin and paclitaxel.
Osimertinib monotherapy, at the dose to be evaluated in this trial, has shown consistent and high objective response rates in the target patient population.
Anti-angiogenic agents targeting the VEGF/VEGFR signalling pathway have been shown to provide additional efficacy when used in combination with first-line platinum-based chemotherapy in several trials in non-squamous NSCLC or in combination with erlotinib as first line therapy in EGFRm positive NSCLC patients. The combination of osimertinib plus an anti-angiogenic agent such as bevacizumab may provide a wider activity against tumours that have developed resistance to EGFR TKI agents by blocking the dual pathways of proliferative signalling and antigenic signalling. Preclinical studies suggested that patients on lower doses of EGFR TKI tend to develop treatment resistance earlier than those who receive higher doses. Therefore the combination may also delay the development of subsequent resistance as the preclinical studies suggested anti-angiogenic agents may increase intratumoural uptake of anti-cancer drugs by changing tumour vessel physiology.
Efficacy and safety data from the osimertinib monotherapy studies have shown promising efficacy and an acceptable safety profile at the recommended dose of 80 mg once daily. The combination of osimertinib with bevacizumab may have the potential to provide additional clinical benefit in terms of increased and/or prolonged disease control and a delay in the emergence of resistance in patients with advanced EGFRm NSCLC who have progressed following a prior EGFR TKI agent, compared against the current standard of care (chemotherapy or another EGFR TKI) or monotherapy of any of the individual agents.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Osimertinib plus Bevacizumab | Experimental | Patients will receive treatment with osimertinib and bevacizumab until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. |
|
| Osimertinib alone | Active Comparator | Patients will receive treatment with osimertinib until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Osimertinib | Drug | Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | PFS is defined as the time from the date of randomisation until documented progression (based on RECIST 1.1 criteria) or death, if progression is not documented. Censoring (for patients without progression/death) will occur at the last tumour assessment if patient is lost to follow-up or refuses further documentation of follow-up. | Evaluated up to approximately 45 months from the randomisation of the first patient. |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR is defined as the percentage of patients reaching a complete or partial response, across all assessment time-points according to RECIST criteria v1.1, during the period from randomisation to termination of trial treatment. | Evaluated up to approximately 45 months from the randomisation of the first patient. |
| Measure | Description | Time Frame |
|---|---|---|
| T790M Evolution in Tissue and Plasma/Serum Between Baseline and Disease Progression (PD) on Trial Treatment. | Tumour tissue blocks, plasma and serum samples will be collected at trial entry and at disease progression on trial treatment. | Available for translational research, following completion of the primary trial research objectives. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Solange Peters, MD | Centre Hospitalier Universitaire Vaudois | Study Chair |
| Rolf Stahel, MD | University Hospital Zuerich, Zurich, Switzerland | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. James Hospital | Dublin | Ireland | ||||
| Mid Western Cancer Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20087963 | Background | Bonomi PD. Implications of key trials in advanced nonsmall cell lung cancer. Cancer. 2010 Mar 1;116(5):1155-64. doi: 10.1002/cncr.24815. | |
| 19671843 | Background | Jackman DM, Miller VA, Cioffredi LA, Yeap BY, Janne PA, Riely GJ, Ruiz MG, Giaccone G, Sequist LV, Johnson BE. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res. 2009 Aug 15;15(16):5267-73. doi: 10.1158/1078-0432.CCR-09-0888. Epub 2009 Aug 11. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Osimertinib Plus Bevacizumab | Patients will receive treatment with osimertinib and bevacizumab until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. Osimertinib: Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. Bevacizumab: Bevacizumab is administered at 15mg/kg intravenously on day 1 of every 3-week cycle. Bevacizumab for intravenous administration will be supplied by Roche. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 14, 2016 | Apr 11, 2023 |
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| Bevacizumab | Drug | Bevacizumab is administered at 15mg/kg intravenously on day 1 of every 3-week cycle. Bevacizumab for intravenous administration will be supplied by Roche. |
|
|
| Disease Control Rate (DCR) | DCR is defined as the percentage of patients reaching a complete or partial response, or disease stabilisation confirmed at subsequent radiological assessment, across all assessment time-points according to RECIST criteria v1.1, during the period from randomisation to termination of trial treatment. | Evaluated up to approximately 45 months from the randomisation of the first patient. |
| Adverse Events | Adverse events, graded by CTCAE version 4.0, will be recorded from date of signature of informed consent until 30 days after all trial treatment discontinuation. | Evaluated up to approximately 45 months from the randomisation of the first patient. |
| Overall Survival (OS) | OS is defined as time from the date of randomisation until death from any cause. Censoring will occur at the last follow-up date. | Evaluated up to approximately 45 months from the randomisation of the first patient. |
| Limerick |
| Ireland |
| VU University Medical Centre | Amsterdam | Netherlands |
| National University Hospital | Singapore | Singapore |
| Tan Tock Seng Hospital | Singapore | Singapore |
| National Cancer Centre | Goyang | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | South Korea |
| Hospital Teresa Herrara | A Coruña | Spain |
| Hospital General Alicante | Alicante | Spain |
| Hospital Sant Pau | Barcelona | Spain |
| ICO Badalona | Barcelona | Spain |
| ICO Hospitalet | Barcelona | Spain |
| OSI Bilbao Basurto | Bilbao | Spain |
| Fund. Jimenez Diaz | Madrid | Spain |
| Hospital de la Princesa | Madrid | Spain |
| Hospital la Paz | Madrid | Spain |
| Hospital Puerta de Hierro | Madrid | Spain |
| Hospital Virgen del Rocio | Seville | Spain |
| Hospital Arnau de Vilanova | Valencia | Spain |
| Hospital General de Valencia | Valencia | Spain |
| Geneva University Hospital (HUG) | Geneva | Switzerland |
| Centre Hospitalier Universitaire Vaudois | Lausanne | Switzerland |
| Kantonsspital St. Gallen | Sankt Gallen | Switzerland |
| Kantonsspital Winterthur | Winterthur | Switzerland |
| UniversitatSpital Zurich | Zurich | Switzerland |
| 21135146 | Background | Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6. |
| 22285168 | Background | Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26. |
| 25271963 | Background | Finlay MR, Anderton M, Ashton S, Ballard P, Bethel PA, Box MR, Bradbury RH, Brown SJ, Butterworth S, Campbell A, Chorley C, Colclough N, Cross DA, Currie GS, Grist M, Hassall L, Hill GB, James D, James M, Kemmitt P, Klinowska T, Lamont G, Lamont SG, Martin N, McFarland HL, Mellor MJ, Orme JP, Perkins D, Perkins P, Richmond G, Smith P, Ward RA, Waring MJ, Whittaker D, Wells S, Wrigley GL. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249-67. doi: 10.1021/jm500973a. Epub 2014 Oct 1. |
| 24981256 | Background | Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol. 2014 Aug;11(8):473-81. doi: 10.1038/nrclinonc.2014.104. Epub 2014 Jul 1. |
| FG001 | Osimertinib Alone | Patients will receive treatment with osimertinib until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. Osimertinib: Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. |
| Received at least one dose of trial treatment | Safety cohort: patients at risk for adverse events and serious adverse events |
|
| On treatment | At database cut-off for final efficacy analysis: February 22, 2021 |
|
| Treatment failures | Osimertinib plus Bevacizumab: 36 toxicities, 29 progressions, 4 other reasons, 3 patient decisions, 2 deaths, 1 investigator decision Osimertinib alone: 3 toxicities, 53 progressions, 1 other reason, 4 patient decisions, 7 deaths, 1 investigator decision |
|
| Never started treatment |
|
| COMPLETED | Still on follow-up at database cut-off for final efficacy analysis: February 22, 2021 |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Osimertinib Plus Bevacizumab | Patients will receive treatment with osimertinib and bevacizumab until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. Osimertinib: Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. Bevacizumab: Bevacizumab is administered at 15mg/kg intravenously on day 1 of every 3-week cycle. Bevacizumab for intravenous administration will be supplied by Roche. |
| BG001 | Osimertinib Alone | Patients will receive treatment with osimertinib until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. Osimertinib: Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| ECOG Performance Status | 0: Fully active, able to carry on all pre-disease performance without restriction; 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2: Ambulatory and capable of all selfcare but unable to carry out any work activities, up and about more than 50% of waking hours. | Count of Participants | Participants |
| |||||||||||||||
| Smoking status | Current smoker: Still smokes cigarettes, Former smoker: Smoked at least 100 cigarettes in the past during the whole life, Never smoker: Smoked 0-99 cigarettes during the whole life. | Count of Participants | Participants |
| |||||||||||||||
| Stage | Stage is based on the 8th TNM classification for NSCLC (American Joint Committee on Cancer). Stage IIIB/C: the tumor is 5 cm or smaller (IIIB) or any size (IIIC) and cancer has spread to lymph nodes above the collarbone on the same side of the chest as the primary tumor or to any lymph nodes on the opposite side of the chest as the primary tumor. Stage IVA: cancer has spread within the chest and/or has spread to 1 area outside of the chest. Stage IVB: cancer has spread outside of the chest to more than 1 place in 1 organ or to more than 1 organ. | Count of Participants | Participants |
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| Use of prior platinum-based chemotherapy | Count of Participants | Participants |
| ||||||||||||||||
| Prior EGFR TKI | TKI: tyrosine kinase inhibitors | Count of Participants | Participants |
| |||||||||||||||
| EGFR mutation type | Histologically or cytologically confirmed exon 19 deletion or exon 21 L858R mutation by a certified local laboratory | Count of Participants | Participants |
| |||||||||||||||
| T790M testing material | Confirmation of T790M mutation determined from biopsy or on serum circulating tumour DNA by a certified local laboratory. These samples must be taken after disease progression on the most recent EGFR TKI regimen. | Count of Participants | Participants |
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| Brain metastasis | Count of Participants | Participants |
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| Liver metastasis | Count of Participants | Participants |
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| Pleural effusion and ascites | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Progression Free Survival (PFS) | PFS is defined as the time from the date of randomisation until documented progression (based on RECIST 1.1 criteria) or death, if progression is not documented. Censoring (for patients without progression/death) will occur at the last tumour assessment if patient is lost to follow-up or refuses further documentation of follow-up. | Efficacy population (Intention-To-Treat cohort of all randomised patients) | Posted | Median | 95% Confidence Interval | months | Evaluated up to approximately 45 months from the randomisation of the first patient. |
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| Secondary | Objective Response Rate (ORR) | ORR is defined as the percentage of patients reaching a complete or partial response, across all assessment time-points according to RECIST criteria v1.1, during the period from randomisation to termination of trial treatment. | Efficacy population (Intention-To-Treat cohort of all randomised patients) | Posted | Count of Participants | Participants | Evaluated up to approximately 45 months from the randomisation of the first patient. |
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| Secondary | Disease Control Rate (DCR) | DCR is defined as the percentage of patients reaching a complete or partial response, or disease stabilisation confirmed at subsequent radiological assessment, across all assessment time-points according to RECIST criteria v1.1, during the period from randomisation to termination of trial treatment. | Efficacy population (Intention-To-Treat cohort of all randomised patients) | Posted | Count of Participants | Participants | Evaluated up to approximately 45 months from the randomisation of the first patient. |
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| Secondary | Adverse Events | Adverse events, graded by CTCAE version 4.0, will be recorded from date of signature of informed consent until 30 days after all trial treatment discontinuation. | Safety population (all patients who received at least 1 dose of trial treatment). | Posted | Count of Participants | Participants | Evaluated up to approximately 45 months from the randomisation of the first patient. |
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| Secondary | Overall Survival (OS) | OS is defined as time from the date of randomisation until death from any cause. Censoring will occur at the last follow-up date. | Efficacy population (Intention-To-Treat cohort of all randomised patients) | Posted | Median | 95% Confidence Interval | months | Evaluated up to approximately 45 months from the randomisation of the first patient. |
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| Other Pre-specified | T790M Evolution in Tissue and Plasma/Serum Between Baseline and Disease Progression (PD) on Trial Treatment. | Tumour tissue blocks, plasma and serum samples will be collected at trial entry and at disease progression on trial treatment. | Patients with available NGS plasma sample. | Posted | Count of Participants | Participants | Available for translational research, following completion of the primary trial research objectives. |
|
Continuously from date of Informed Consent signature until 30 days after all treatments discontinuation, up to approximately 45 months from the randomisation of the first patient.
Adverse event (AE) is defined as any untoward medical occurrence that occurs from the date of signature of informed consent until 30 days after all trial treatment discontinuation, regardless of whether it is considered related to a medication. Adverse events are classified according to CTCAE version 4.0.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Osimertinib Plus Bevacizumab | Patients will receive treatment with osimertinib and bevacizumab until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. Osimertinib: Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. Bevacizumab: Bevacizumab is administered at 15mg/kg intravenously on day 1 of every 3-week cycle. Bevacizumab for intravenous administration will be supplied by Roche. | 46 | 78 | 33 | 76 | 76 | 76 |
| EG001 | Osimertinib Alone | Patients will receive treatment with osimertinib until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit. Osimertinib: Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration. | 43 | 77 | 27 | 77 | 76 | 77 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Gastric perforation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Bronchopulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Laryngeal hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Splenic infection | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Drug overdose | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Lung infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Bronchial infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| COVID-19 infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Enterocolitis infectious | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Hepatitis caused by COVID-19 infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
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| Influenza | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Influenza A | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Necrotising fasciitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pleural infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Ischemia cerebrovascular | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Stroke | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hematuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Mania | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Heart failure | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pleurodesis of malignant pleural effusion | Surgical and medical procedures | CTCAE (4.0) | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
| |
| Hepatic failure | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Autoimmune disorder | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Gastric carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Serum amylase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Electrocardiogram QT corrected interval prolonged | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| GGT increased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Heidi Roschitzki, PhD | ETOP IBCSG Partners Foundation | +41 31 511 94 00 | heidi.roschitzki@etop.ibcsg.org |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 23, 2020 | Apr 3, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000596361 | osimertinib |
| D000068258 | Bevacizumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Non-Asian |
|
| 1 |
|
| 2 |
|
| Former smoker |
|
| Never smoked |
|
| IVA/B |
|
| Missing |
|
| Afatinib/dacomitinib |
|
| Other |
|
| Exon 21 L858R |
|
| Tumour |
|
| No |
|
| No |
|
| No |
|
|
|
|
|
|
|
|
|
|
|