EGFR Gene MutationPhase 1/2NCT02954523
Dasatinib and Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer With EGFR Mutations
A Phase 1/2 study testing Dasatinib and Osimertinib in people with EGFR Gene Mutation and Nonsmall Cell Lung Cancer, run by Chul Kim at 2 sites in United States.
Trial summary
This is a study for patients with advanced non-small cell lung cancer with changes to their cancer cells called EGFR mutations. Mutated EGFR is important in the growth of cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR Gene Mutation, Nonsmall Cell Lung Cancer
- What is being tested?
- Dasatinib and Osimertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2016to 3 Mar 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have cytologically or histologically confirmed advanced NSCLC. Patients with mixed histology containing a small cell lung cancer component are not eligible.
- Patients must have adequate archival material from a previous biopsy to determine EGFR mutation status and Cripto-1 expression, or undergo a biopsy of fresh tissue of the primary cancer or a metastatic site in order to make these determinations, if archival material is not available.
- Presence of sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q). Patients with the T790M mutation will also be eligible.
- No prior treatment with an EGFR TKI for the advanced NSCLC.
- ECOG performance status of 0-2.
- Patients must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 7.1.2 for the evaluation of measurable disease.
Show all 12Show fewer
- Prior systemic treatment is allowed, but toxicities of prior therapy must be resolved to grade 1 or less as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- Adequate organ and bone marrow function (hemoglobin > 9 g/dL; absolute neutrophil count > 1.5 x 109/L; platelet counts > 100 x 109/L; serum bilirubin < 2 x ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN or < 5 x ULN if liver metastases; calculated creatinine clearance > 50 mL/min).
- No uncontrolled arrhythmia; no myocardial infarction in the last 6 months.
- Life expectancy of at least 12 weeks.
- Age > 18 years.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- Patients who have had radiotherapy (except for palliative reasons), immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas or mitomycin) before treatment, or those who have ongoing toxic manifestations of previous treatments, with the exception of alopecia, of grade higher than 1.
- Major thoracic or abdominal surgery from which the patient has not sufficiently recovered yet.
- Untreated and uncontrolled second tumor in the past 2 years.
- Logistical or psychological hindrance to participation in clinical research.
- Patients with untreated symptomatic brain metastases may be eligible if symptoms do not require urgent surgery or radiation, and no steroids are necessary.
- Patients with evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung disease).
Show all 23Show fewer
- Pleural or pericardial effusions of any grade at study entry. Subjects previously diagnosed with pleural/pericardial effusion of any grade resolved at the time of study entry are allowed.
- Ability to become pregnant (or already pregnant or lactating). Women and men who want to participate have to agree to use two highly effective forms of contraceptive prior to study entry, for the duration of study participation, and for 30 days following completion of therapy, to be eligible. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
- At high medical risk because of non-malignant systemic disease including uncontrolled infection.
- Known to be serologically positive for hepatitis B, hepatitis C or HIV.
- Uncontrolled or significant cardiovascular disease, including any of the following:
- QTc interval > 480 msec (mean value and manually verified) at 3 or more time points within a 24 hour period if necessary.
- Diagnosed or expected congenital long QT syndrome.
- Concurrent congestive heart failure, prior history of class III/IV cardiac disease (New York Heart Association).
- Left ventricular ejection fraction < 50%
- Prior history of cardiac ischemia or cardiac arrhythmia within the last 6 months. Coronary angioplasty or stenting in the previous 12 months.
- Any history of second or third degree heart block (may be eligible if the subject currently has a pacemaker).
- Uncontrolled hypertension defined as inability to maintain blood pressure below the limit of 140/90 mmHg.
- Known pulmonary hypertension.
- History of significant bleeding disorder unrelated to CML, including:
- Diagnosed congenital bleeding disorders (e.g. von Willebrand's disease)
- Diagnosed acquired bleeding disorder within one year (e.g. acquired anti-factor VII antibodies)
- Any other medical condition that in the Investigator's opinion would not make the patient a good candidate for the study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
John Theurer Cacner Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, 20007
About this study
Official title: Phase I/II Study of Dasatinib and Osimertinib (AZD9291) in Patients With Advanced Non-small Cell Lung Cancer With EGFR Mutations
This is a study for patients with advanced non-small cell lung cancer with changes to their cancer cells called EGFR mutations. Mutated EGFR is important in the growth of cancer cells. Medical studies have shown that patients with EGFR mutation-positive lung cancer gain more benefit from targeted therapy drugs such as EGFR inhibitors than with standard chemotherapy. However, a significant proportion of patients carrying these sensitizing mutations do not respond well to the first-generation EGFR-TKIs (erlotinib and gefitinib), indicating the existence of intrinsic resistance mechanisms. Moreover, despite initial response to EGFR-TKIs, acquired resistance is inevitable in all patients.
The investigators have recently shown that Cripto-1 overexpression in EGFR mutant NSCLC contributes to the intrinsic resistance to EGFR-TKIs through activation of the SRC oncogene. They have also shown that a combination of an EGFR-TKI (both erlotinib and osimertinib) and a Src inhibitor are synergistic in Cripto-1 overexpressing tumors in the laboratory.
Read more
This study will be testing a combination of two drugs, dasatinib and osimertinib, to overcome resistance to EGFR-TKIs. Osimertinib (AZD9291) is a third-generation EGFR-TKI, which selectively blocks the activity of EGFR mutants, but spares that of wild type. The advantage of using osimertinib is that it inhibits not only the sensitizing EGFR mutations, but also the T790M mutant, which is the most common mechanism of acquired resistance. Dasatinib is a potent, orally available ABL1/SRC TKI, approved for the treatment of chronic myeloid leukemia (CML) in first-line and in patients with imatinib-resistant disease or intolerant, and is being actively studied in patients with advanced solid tumors.
The first part of the study will involve finding the highest dose of dasatinib that can be given with osimertinib without causing severe side effects, finding out the side effects seen by giving dasatinib at different dose levels with osimertinib, and measuring the levels of dasatinib and osimertinib in blood at different dose levels. The second part will determine the effects of the combination of dasatinib and osimertinib and determine if the amount of Cripto-1 protein in your tumor or blood makes you more likely to have a good response to the combination of dasatinib and osimertinib.
Read the detailed description
The treatment of patients with advanced non-small cell lung cancer is unsatisfactory. The median survival is approximately 12 months with standard chemotherapy. Epidermal growth factor receptor (EGFR) mutations are one of the most frequent genetic abnormalities observed in non-small cell lung cancer (NSCLC), especially in adenocarcinoma subtype. The most predominant EGFR mutations are in-frame deletions in exon-19 and L858R missense mutation, and patients carrying these mutations are mostly sensitive to the EGFR-targeted tyrosine kinase inhibitors (TKIs). However, a significant proportion of patients carrying these sensitizing mutations do not respond well to the first generation EGFR-TKIs (erlotinib and gefitinib), indicating the existence of intrinsic resistance mechanisms. Moreover, despite initial response to EGFR-TKIs, acquired resistance is inevitable in all patients. Novel treatment strategies need to be developed to overcome resistance to EGFR-TKIs. The investigators have recently shown that Cripto-1 overexpression in EGFR mutant NSCLC contributes to the intrinsic resistance to EGFR-TKIs through SRC activation. They have also shown that a combination of an EGFR-TKI (both erlotinib and AZD9291) and a Src inhibitor are synergistic in vitro and in vivo in Cripto-1 overexpressing tumors. AZD9291 is a third-generation EGFR-TKI, which selectively blocks the activity of EGFR mutants but spares that of wild type. The advantage of using AZD9291 is that it inhibits not only the mutants of exon-19 deletion and L858R, but also the T790M mutant, which is the most common mechanism of acquired resistance. Dasatinib is a potent, orally available ABL1/SRC TKI, approved for the treatment of chronic myeloid leukemia (CML) in first-line and in patients with imatinib-resistant disease or intolerant, and is being actively studied in patients with advanced solid tumors.
This is an open-label, non-randomized, prospective phase I/II trial. The phase I portion will follow a standard 3+3 design for the phase I portion and one-sample group sequential multiple testing procedure for the phase II portion.
- Conditions
- EGFR Gene Mutation, Nonsmall Cell Lung Cancer
- Being tested
- Dasatinib, Osimertinib
- Keywords
- NSCLC, Non-small cell, Lung Cancer, Dasatinib, Osimertinib, AZD9291, EGFR Mutations, Epidermal growth factor receptor (EGFR)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called BMS-354825
oral every day
OsimertinibDrug
Also called AZD9291
oral every day
| Study group | Role | What they receive |
|---|---|---|
| Phase I- Dasatanib Dose Level 1 | Experimental | Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule.
Dasatinib is taken orally and will be given at up to 4 dose levels. Level 1 (the starting dose - 50 mg twice daily).
Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2).
There is no limit to the number of cycles a patient can receive. Receives: Drug: Dasatinib; Drug: Osimertinib |
| Phase I- Dasatanib Dose Level 2 | Experimental | Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule.
Dasatinib is taken orally and will be given at up to 4 dose levels. Level 2 (70 mg twice daily).
Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2).
There is no limit to the number of cycles a patient can receive. Receives: Drug: Dasatinib; Drug: Osimertinib |
| Phase I- Dasatanib Dose Level -1 | Experimental | Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule.
Dasatinib is taken orally and will be given at up to 4 dose levels. Level -1 (70 mg once daily).
Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2).
There is no limit to the number of cycles a patient can receive. Receives: Drug: Dasatinib; Drug: Osimertinib |
| Phase I- Dasatanib Dose Level -2 | Experimental | Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule.d
Dasatinib is taken orally and will be given at up to 4 dose levels. Level -2 (50 mg once daily).
Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2).
There is no limit to the number of cycles a patient can receive. Receives: Drug: Dasatinib; Drug: Osimertinib |
| Phase II- Maximum tolerated dose | Experimental | The phase II portion of the study will use the maximum tolerated dose of dasatinib determined in the phase I portion. Osimertinib (AZD9291) will be given at the same 80mg dose as the phase I portion. There is no limit to the number of cycles a patient can receive. Receives: Drug: Dasatinib; Drug: Osimertinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I : Number of Patients With Drug-related Adverse Events as Assessed by CTCAEv4.0
Number of patients with drug related adverse events (Dose Limiting Toxicities) on dasatinib when given in combination with osimertinib
Measured: Cycle 1 (28 day cycle)
Phase II : Number of Patients That do Not Progress According to RECIST v1.1
The rate of patients non-responding (progressive disease or stable disease lasting 4 months or less) to the combination of osimertinib and dasatinib
Measured: 9 months
Secondary outcomes (5)
Number of Patients With Treatment-related Adverse Events in the Phase II Study
Number of patients with treatment-related adverse events in the phase II study, who are treated at the same dose that has been selected based on the phase I part
Measured: 18 months
Concentration of Osimertinib in Blood (Cmax)
To describe the concentration of osimertinib when administered with dasatinib. Blood is obtained from patients before each cycle and 4 hours after start of the first 2 cycles.
Measured: 0 hour, 4 hours post dose
Progression-free Survival
Determination of the time between the start of the experimental treatment and progression of the tumor
Measured: 3 years
Overall Survival
From the date of start of the experimental treatment until the date of death from any cause, whichever came first, assessed up to 47 months.
Measured: 47 months
Duration of Response
Determination of the duration of the response to the treatment, calculated from start of treatment in case of partial response and from the declaration of complete response in case of complete response. The end of the response will be when the tumor progresses
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionAug 2018
- Study completion3 Mar 2023
Why it stopped: Lack of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EGFR Gene MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chul Kim
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Bristol-Myers Squibb, Walter Reed National Military Medical Center, Hackensack Meridian Health
- Responsible party
- Sponsor-investigator, Chul Kim, Georgetown University
- Investigators
- Giuseppe Giaccone, MD PhD, Study chair, Associate Director for Clinical Research, Lombardi Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02954523
- Sponsor's protocol ID
- 2016-0493
- Status last verified
- Jul 2024
- First submitted
- 25 Oct 2016
- Last updated
- 5 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kim C, Liu SV, Crawford J, Torres T, Chen V, Thompson J, Tan M, Esposito G, Subramaniam DS, Giaccone G. A Phase I Trial of Dasatinib and Osimertinib in TKI Naive Patients With Advanced EGFR-Mutant Non-Small-Cell Lung Cancer. Front Oncol. 2021 Sep 8;11:728155. doi: 10.3389/fonc.2021.728155. eCollection 2021.
PubMed 34568058
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Dasatinib and Osimertinib (AZD9291) in Patients With Advanced Non-small Cell Lung Cancer With EGFR Mutations
- ClinicalTrials.gov ID
- NCT02954523
- Acronym / sponsor ID
- 2016-0493
- Conditions
- EGFR Gene Mutation, Nonsmall Cell Lung Cancer
- Keywords
- NSCLC, Non-small cell, Lung Cancer, Dasatinib, Osimertinib, AZD9291, EGFR Mutations, Epidermal growth factor receptor (EGFR)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Chul KimUniversity, hospital or other
- Collaborators
- AstraZeneca, Bristol-Myers Squibb, Walter Reed National Military Medical Center, Hackensack Meridian Health
- Study start
- Oct 2016 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- 3 Mar 2023 (actual)
- First posted
- 3 Nov 2016 (estimated)
- Results
- Posted 5 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study for patients with advanced non-small cell lung cancer with changes to their cancer cells called EGFR mutations. Mutated EGFR is important in the growth of cancer cells. Medical studies have shown that patients with EGFR mutation-positive lung cancer gain more benefit from targeted therapy drugs such as EGFR inhibitors than with standard chemotherapy. However, a significant proportion of patients carrying these sensitizing mutations do not respond well to the first-generation EGFR-TKIs (erlotinib and gefitinib), indicating the existence of intrinsic resistance mechanisms. Moreover, despite initial response to EGFR-TKIs, acquired resistance is inevitable in all patients.
The investigators have recently shown that Cripto-1 overexpression in EGFR mutant NSCLC contributes to the intrinsic resistance to EGFR-TKIs through activation of the SRC oncogene. They have also shown that a combination of an EGFR-TKI (both erlotinib and osimertinib) and a Src inhibitor are synergistic in Cripto-1 overexpressing tumors in the laboratory.
This study will be testing a combination of two drugs, dasatinib and osimertinib, to overcome resistance to EGFR-TKIs. Osimertinib (AZD9291) is a third-generation EGFR-TKI, which selectively blocks the activity of EGFR mutants, but spares that of wild type. The advantage of using osimertinib is that it inhibits not only the sensitizing EGFR mutations, but also the T790M mutant, which is the most common mechanism of acquired resistance. Dasatinib is a potent, orally available ABL1/SRC TKI, approved for the treatment of chronic myeloid leukemia (CML) in first-line and in patients with imatinib-resistant disease or intolerant, and is being actively studied in patients with advanced solid tumors.
The first part of the study will involve finding the highest dose of dasatinib that can be given with osimertinib without causing severe side effects, finding out the side effects seen by giving dasatinib at different dose levels with osimertinib, and measuring the levels of dasatinib and osimertinib in blood at different dose levels. The second part will determine the effects of the combination of dasatinib and osimertinib and determine if the amount of Cripto-1 protein in your tumor or blood makes you more likely to have a good response to the combination of dasatinib and osimertinib.
Detailed description
The treatment of patients with advanced non-small cell lung cancer is unsatisfactory. The median survival is approximately 12 months with standard chemotherapy. Epidermal growth factor receptor (EGFR) mutations are one of the most frequent genetic abnormalities observed in non-small cell lung cancer (NSCLC), especially in adenocarcinoma subtype. The most predominant EGFR mutations are in-frame deletions in exon-19 and L858R missense mutation, and patients carrying these mutations are mostly sensitive to the EGFR-targeted tyrosine kinase inhibitors (TKIs). However, a significant proportion of patients carrying these sensitizing mutations do not respond well to the first generation EGFR-TKIs (erlotinib and gefitinib), indicating the existence of intrinsic resistance mechanisms. Moreover, despite initial response to EGFR-TKIs, acquired resistance is inevitable in all patients. Novel treatment strategies need to be developed to overcome resistance to EGFR-TKIs. The investigators have recently shown that Cripto-1 overexpression in EGFR mutant NSCLC contributes to the intrinsic resistance to EGFR-TKIs through SRC activation. They have also shown that a combination of an EGFR-TKI (both erlotinib and AZD9291) and a Src inhibitor are synergistic in vitro and in vivo in Cripto-1 overexpressing tumors. AZD9291 is a third-generation EGFR-TKI, which selectively blocks the activity of EGFR mutants but spares that of wild type. The advantage of using AZD9291 is that it inhibits not only the mutants of exon-19 deletion and L858R, but also the T790M mutant, which is the most common mechanism of acquired resistance. Dasatinib is a potent, orally available ABL1/SRC TKI, approved for the treatment of chronic myeloid leukemia (CML) in first-line and in patients with imatinib-resistant disease or intolerant, and is being actively studied in patients with advanced solid tumors.
This is an open-label, non-randomized, prospective phase I/II trial. The phase I portion will follow a standard 3+3 design for the phase I portion and one-sample group sequential multiple testing procedure for the phase II portion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Phase I- Dasatanib Dose Level 1 | Experimental | Drug: Dasatinib, Drug: OsimertinibOsimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at up to 4 dose levels. Level 1 (the starting dose - 50 mg twice daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive. |
| Phase I- Dasatanib Dose Level 2 | Experimental | Drug: Dasatinib, Drug: OsimertinibOsimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at up to 4 dose levels. Level 2 (70 mg twice daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive. |
| Phase I- Dasatanib Dose Level -1 | Experimental | Drug: Dasatinib, Drug: OsimertinibOsimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at up to 4 dose levels. Level -1 (70 mg once daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive. |
| Phase I- Dasatanib Dose Level -2 | Experimental | Drug: Dasatinib, Drug: OsimertinibOsimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule.d Dasatinib is taken orally and will be given at up to 4 dose levels. Level -2 (50 mg once daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive. |
| Phase II- Maximum tolerated dose | Experimental | Drug: Dasatinib, Drug: OsimertinibThe phase II portion of the study will use the maximum tolerated dose of dasatinib determined in the phase I portion. Osimertinib (AZD9291) will be given at the same 80mg dose as the phase I portion. There is no limit to the number of cycles a patient can receive. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have cytologically or histologically confirmed advanced NSCLC. Patients with mixed histology containing a small cell lung cancer component are not eligible.
- Patients must have adequate archival material from a previous biopsy to determine EGFR mutation status and Cripto-1 expression, or undergo a biopsy of fresh tissue of the primary cancer or a metastatic site in order to make these determinations, if archival material is not available.
- Presence of sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q). Patients with the T790M mutation will also be eligible.
- No prior treatment with an EGFR TKI for the advanced NSCLC.
- ECOG performance status of 0-2.
Key exclusion criteria (23 listed)
- Patients who have had radiotherapy (except for palliative reasons), immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas or mitomycin) before treatment, or those who have ongoing toxic manifestations of previous treatments, with the exception of alopecia, of grade higher than 1.
- Major thoracic or abdominal surgery from which the patient has not sufficiently recovered yet.
- Untreated and uncontrolled second tumor in the past 2 years.
- Logistical or psychological hindrance to participation in clinical research.
- Patients with untreated symptomatic brain metastases may be eligible if symptoms do not require urgent surgery or radiation, and no steroids are necessary.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DasatinibAlso: BMS-354825oral every day | Drug | Phase I- Dasatanib Dose Level -1, Phase I- Dasatanib Dose Level -2, Phase I- Dasatanib Dose Level 1, Phase I- Dasatanib Dose Level 2, Phase II- Maximum tolerated dose |
| OsimertinibAlso: AZD9291oral every day | Drug | Phase I- Dasatanib Dose Level -1, Phase I- Dasatanib Dose Level -2, Phase I- Dasatanib Dose Level 1, Phase I- Dasatanib Dose Level 2, Phase II- Maximum tolerated dose |
Primary outcome
Phase I : Number of Patients With Drug-related Adverse Events as Assessed by CTCAEv4.0
Time frame: Cycle 1 (28 day cycle)
Number of patients with drug related adverse events (Dose Limiting Toxicities) on dasatinib when given in combination with osimertinib
Phase II : Number of Patients That do Not Progress According to RECIST v1.1
Time frame: 9 months
The rate of patients non-responding (progressive disease or stable disease lasting 4 months or less) to the combination of osimertinib and dasatinib
5 secondary outcomes
Number of Patients With Treatment-related Adverse Events in the Phase II Study
Time frame: 18 months
Concentration of Osimertinib in Blood (Cmax)
Time frame: 0 hour, 4 hours post dose
Progression-free Survival
Time frame: 3 years
Overall Survival
Time frame: 47 months
Duration of Response
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34568058Kim C, Liu SV, Crawford J, Torres T, Chen V, Thompson J, Tan M, Esposito G, Subramaniam DS, Giaccone G. A Phase I Trial of Dasatinib and Osimertinib in TKI Naive Patients With Advanced EGFR-Mutant Non-Small-Cell Lung Cancer. Front Oncol. 2021 Sep 8;11:728155. doi: 10.3389/fonc.2021.728155. eCollection 2021.
- Individual participant dataSharing planned: No
Related trials for EGFR Gene Mutation
RecruitingPhase 1/2
A Study of VRN110755 in Patients With EGFR-Mutant Non-Small Cell Lung Cancer
EGFR-Mutant Non-Small Cell Lung Cancer
RecruitingPhase 3
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
PIK3CA Mutation, HER2- Negative Breast Cancer
RecruitingPhase 1/2
Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration
Solid Tumors
Active, not recruitingPhase 1
Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC
EGFR-mutant Non-small Cell Lung Cancer
RecruitingPhase 3
A Study to Learn More About How Well Sevabertinib Works and How Safe it is Compared With Standard Treatment, in Participants Who Have Advanced Non-small Cell Lung Cancer (NSCLC) With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Non-small Cell Lung Cancer, HER2 Mutation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Giaccone, MD PhD study chair
Associate Director for Clinical Research, Lombardi Comprehensive Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dasatinib and Osimertinib in people with EGFR Gene Mutation and Nonsmall Cell Lung Cancer, run by Chul Kim at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I : Number of Patients With Drug-related Adverse Events as Assessed by CTCAEv4.0 (time frame: Cycle 1 (28 day cycle)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02954523, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2024.