Non-Small Cell Lung CancerPhase 2OCELOTNCT04335292
Osimertinib Then Chemotherapy in EGFR-mutated Lung Cancer with Osimertinib Third-line Rechallenge
A Phase 2 study testing Osimertinib First-Line, Platinum + Pemetrexed Chemotherapy Second-Line and Osimertinib Third-Line in people with Non-Small Cell Lung Cancer, run by Mark Vincent at 10 sites in Canada.
Trial summary
This phase II single-armed study will examine the clinical utility of retreating patients with osimertinib, in the third-line, following first-line treatment with osimertinib and second-line treatment with platinum and pemetrexed chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Osimertinib First-Line, Platinum + Pemetrexed Chemotherapy Second-Line and Osimertinib Third-Line
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 10 sitesCanada
- Study dates
- 6 Jan 2021to 1 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Provision of informed consent prior to any study specific procedures
- Male or female patients of at least 18 years of age
- Pathologically proven advanced non-small cell lung cancer (i.e. stage M1 (metastasis), or earlier stages if unfit or unsuitable for radical treatment). Patients must have a tissue diagnosis of lung cancer, either by histology or cytology, however, in the event that there is insufficient tissue for molecular analysis, mutations identified in circulating tumor deoxyribonucleic acid (ctDNA) analysis will be permitted.
- Patients must have a known activating Epidermal Growth Factor Receptor (EGFR) mutation. Atypical Epidermal Growth Factor Receptor (EGRF) mutations are allowed. Atypical mutations may require sponsor approval. Exon 20 insertions will not be allowed.
- Patients must have an Eastern Cooperative Oncology Group/World Health Organisation Performance Status (ECOG/WHO-PS) of 0-3 and an expectation that they could potentially receive second-line chemotherapy
- Patients must have an expected life expectancy of at least 12 weeks
Show all 19Show fewer
- Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- Women under 50 years old are consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) levels in the post-menopausal range for the institution
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- Male subjects should be willing to use barrier contraception
- Additional Criteria for patients enrolling after first-line progression and prior to second-line chemotherapy::
- Subjects must have complete baseline demographic data available (age at diagnosis of metastatic non-small cell lung cancer, ethnicity, smoking status, sex, history of brain metastasis) and the following must be available (if applicable):
- o Date of first dose of osimertinib, date that first-line osimertinib was permanently discontinued, date of first-line progression.
- Additional Criteria for patients enrolling at the time of third-line osimertinib rechallenge:
- Subjects must have complete baseline demographic data available (age at diagnosis of metastatic non-small cell lung cancer (NSCLC), ethnicity, smoking status, sex, history of brain metastasis) and the following must be available (if applicable):
- o Date of first dose of osimertinib, date that first-line osimertinib was permanently discontinued, date of first-line progression, date second-line chemotherapy was started, which platinum chemotherapy was given, if pemetrexed maintenance was given, date that second-line chemotherapy was permanently stopped, and date of progression on second-line treatment.
- Patients must have received platinum/ pemetrexed chemotherapy in the second-line chemotherapy
- Subjects must have measurable disease defined as at least one measurable lesion that can be accurately assessed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) at baseline and follow up visits.Subjects must have measurable disease defined as at least one measurable lesion that can be accurately assessed by Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) at baseline and follow up visits.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or involved staff at the study site).
- A second invasive malignancy in the previous three years, other than localized non-melanoma skin cancer, which might be confused with the Epidermal Growth Factor Receptor (EGFR) mutated lung cancer.
- Any other serious and uncontrolled medical or psychiatric condition which would likely interfere in the conduct of the study.
- Pregnancy or lactation
- Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
- Currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of Cytochrome P450 3A4 (CYP3A4) (at least 3 weeks prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on Cytochrome P450 3A4 (CYP3A4).
Show all 29Show fewer
- Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia and grade 2, prior platinum-therapy-related neuropathy.
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
- Patients with spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic.
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
- Past medical history of Interstitial Lung Disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.
- Inadequate bone marrow reserve or organ function (as demonstrated by any of the following laboratory values: absolute neutrophil count less than1.5 x 10 to the power of 9/L, platelet count less than 100 x 10 to the power of 9/L, haemoglobin less than 90 g/L), alanine aminotransferase greater than 2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases; aspartate aminotransferase greater than 2.5 times ULN if no demonstrable liver metastases or greater than 5 times ULN in the presence of liver metastases; total bilirubin greater than 1.5 times ULN if no liver metastases or greater than 3 times ULN in the presence of documented Gilbert's Syndrome [unconjugated hyperbilirubinaemia] or liver metastases; serum creatinine greater than 1.5 times ULN concurrent with creatinine clearance less than 50 mL/min [measured or calculated by Cockcroft and Gault equation]-confirmation of creatinine clearance is only required when creatinine is greater than 1.5 times ULN.
- History of hypersensitivity to any of the active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
- 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.
- Previous adjuvant cytotoxic chemotherapy within the 6 months prior to enrollment.
- Previous adjuvant anti programmed cell death protein 1(anti-PD-1) or anti programmed death-ligand 1 (anti-PD-L1) therapy within 90 days prior to enrollment.
- For patients enrolling prior to first-line treatment with osimertinib:
- Any previous systemic therapy for Epidermal Growth Factor Receptor mutated (EGFR+) advanced Non-Small Cell Lung Cancer (aNSCLC).
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) greater than 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities [including serum/plasma potassium less than the Lower Limit of Normal (LLN), serum/plasma magnesium greater than the Lower Limit of Normal (LLN), serum/plasma calcium less than the Lower Limit of Normal (LLN)], congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes.
- For patients enrolling after progression on first-line osimertinib and prior to second-line chemotherapy all patients must have:
- Received osimertinib in the first-line and no other systemic therapy for their Epidermal Growth Factor Receptor mutated (EGFR+) Advanced Non-Small Cell Lung Cancer (aNSCLC).
- For patients enrolling at the time of third-line osimertinib rechallenge all patients must have:
- Received osimertinib in the first-line followed by second-line platinum (carboplatin/cisplatin) with pemetrexed (pemetrexed maintenance is permitted), and no other systemic therapy for their Epidermal Growth Factor Receptor mutated (EGFR+) advanced Non-Small Cell Lung Cancer.
- Received a minimum of 1 dose of platinum (carboplatin/cisplatin) with pemetrexed.
- AND
- At least 90 days have lapsed since the last dose of first-line osimertinib.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Daniel Breadner, MD contact
10 sites in 1 country
Canada10 sites, 10 recruiting
- Recruiting
William Osler Health System
Brampton, Ontario, L6R 3J7
Parneet Cheema, MD, 905-494-6542
- Recruiting
Hamilton Health Sciences Centre, Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2
Rosalyn Juergens, MD, 905-387-9495
- Recruiting
Grand River Regional Cancer Centre
Kitchener, Ontario, N2G 1G3
Mario Valdes, MD, 519-749-4300
- Recruiting
London Regional Cancer Program of the Lawson Health Research Institute
London, Ontario, N6A 5W9
Mark Vincent, MD, 519-685-8640, Mark.Vincent@lhsc.on.ca
Daniel Breadner, MD, 519-685-8640, Daniel.Breadner@lhsc.on.ca
- Recruiting
Durham Regional Cancer Centre, Lakeridge Health
Oshawa, Ontario, L1G 2B9
Jeffrey Rothenstein, MD, 905-576-8711
- Recruiting
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Paul Wheatley-Price, MD, 613-737-7700
- Recruiting
Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5
Ines Menjak, MD, 416-480-5248
- Recruiting
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
Geoffrey Liu, MD, 416-946-2000
- Recruiting
BC Cancer Agency
Vancouver, British Columbia, V5Z 4E6
Sophie Sun, MD, 604-877-6000
- Recruiting
Lions Gate Hospital
Vancouver, British Columbia, V7L 2L7
Puneet Bains, MD, 604-988-3131
About this study
This phase II single-armed study will examine the clinical utility of retreating patients with osimertinib, in the third-line, following first-line treatment with osimertinib and second-line treatment with platinum and pemetrexed chemotherapy. The current standard of care for first-line Epidermal Growth Factor Receptor (EGFR) mutated Advanced Non-Small Cell Lung Cancer (aNSCLC) is osimertinib, followed by cytotoxic chemotherapy.
The repeat of osimertinib following previous treatment failure is investigational, although supported by scientific rationale. The dosing and scheduling of osimertinib follows its use in approved settings. The investigators examine its tolerability and efficacy in this setting to ensure osimertinib is a safe third-line option for patients with Epidermal Growth Factor Receptor mutated (EGFR+) Advanced Non-Small Cell Lung Cancer(aNSCLC).
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- Osimertinib First-Line, Platinum + Pemetrexed Chemotherapy Second-Line, Osimertinib Third-Line
- Keywords
- Epidermal Growth Factor Receptor Mutation, Advanced Non-Small Cell Lung Cancer
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Osimertinib First-LineDrug
Osimertinib, 80 mg, oral, daily
Platinum + Pemetrexed Chemotherapy Second-LineDrug
Platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed are prescribed as per institutional standards.
Osimertinib Third-LineDrug
Rechallenge with osimertinib, 80 mg, oral, daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | First-line treatment = osimertinib, 80 mg, oral, daily; Second-line treatment = platinum (carboplatin or cisplatin) + pemetrexed chemotherapy, prescribed as per institutional standards; Third-line treatment = osimertinib rechallenge, 80 mg, oral, daily.
Patients may enter the study at first-line treatment, second-line treatment, or third-line treatment. This is dependent on meeting the eligibility criteria. Receives: Drug: Osimertinib First-Line; Drug: Platinum + Pemetrexed Chemotherapy Second-Line; Drug: Osimertinib Third-Line |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate according to Response Evaluation Criteria in Solid Tumors version 1.1
Objective Response Rate will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Objective Response Rate is the percent of subjects with measurable disease with at least one visit response of complete response or partial response.
Measured: End of study (approximately 4 years)
Secondary outcomes (17)
Progression Free Survival according to Response Evaluation Criteria in Solid Tumors version 1.1
Progression Free Survival will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression Free Survival is the time from the first dose of osimertinib until the date of objective disease progression or death (by any cause in the absence of progression).
Measured: End of study (approximately 4 years)
Duration of Response according to Response Evaluation Criteria in Solid Tumors version 1.1
Duration of Response will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Duration of Response is the time from the date of first documented response until date of documented progression or death (in the absence of disease progression), in the third-line setting (osimertinib re-challenge).
Measured: End of study (approximately 4 years)
Disease Control Rate according to Response Evaluation Criteria in Solid Tumors version 1.1
Disease Control Rate will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Disease Control Rate is the percentage of subjects who have a best overall response of complete response or partial response or stable disease.
Measured: End of study (approximately 4 years)
Tumor Shrinkage according to Response Evaluation Criteria in Solid Tumors version 1.1
Tumor Shrinkage will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Measured: End of study (approximately 4 years)
Overall Survival
Overall Survival is the time from the date of the first osimertinib dose rechallenge (third line setting), until death due to any cause.
Measured: End of study (approximately 4 years)
Time to Treatment Failure
Time to Treatment Failure is the time from first dose of osimertinib rechallenge (third-line setting), until the date of objective disease progression leading to the decision to proceed with the next line of systemic therapy, or permanently forego antineoplastic system therapy, or death (by any cause in the absence of progression).
Measured: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Health Related Quality of Life Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30
The effects of osimertinib on health related quality of life will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30).
The EORTC QLQ-C30 is a questionnaire consisting of 30 items measuring subjects general cancer symptoms and functioning. Responses regarding function and symptoms are on a scale of 1 (not at all) to 4 (very much). Also included are questions about overall health and quality of life. Responses are on a scale of 1 (very poor) to 7 (excellent).
Measured: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Health Related Quality of Life Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-LC 13
The effects of osimertinib on health related quality of life will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items (EORTC QLQ-LC13).
The EORTC QLQ-LC13 is a complementary questionnaire to the EORTC QLQ-C30, measuring lung cancer symptoms. Responses regarding symptoms are on a scale of 1 (not at all) to 4 (very much).
Measured: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Disease-Related Symptoms Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires EORTC QLQ-C30
The effects of osimertinib on disease-related symptoms will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30).
The EORTC QLQ-C30 is a questionnaire consisting of 30 items measuring subjects general cancer symptoms and functioning. Responses regarding function and symptoms are on a scale of 1 (not at all) to 4 (very much). Also included are questions about overall health and quality of life. Responses are on a scale of 1 (very poor) to 7 (excellent).
Measured: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Disease-Related Symptoms Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-LC 13
The effects of osimertinib on disease-related symptoms will be measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 items (EORTC QLQ-LC13).
The EORTC QLQ-LC13 is a complementary questionnaire to the EORTC QLQ-C30, measuring lung cancer symptoms. Responses regarding symptoms are on a scale of 1 (not at all) to 4 (very much).
Measured: End of study (approximately 4 years)
Objective Response Rate in the Atypical Epidermal Growth Factor Receptor Mutation Population
Objective Response Rate in the atypical Epidermal Growth Factor Receptor (EGFR) mutation population will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), in both the first line and third line settings. Objective Response Rate is the percent of subjects with measurable disease with at least one visit response of complete response or partial response.
Measured: End of study (approximately 4 years)
Progression Free Survival according to Response Evaluation Criteria in Solid Tumors in the Atypical Epidermal Growth Factor Receptor Population
Progression Free Survival in the atypical Epidermal Growth Factor Receptor (EGFR) population will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), in both the first line and third line settings. Progression Free Survival is the time from the first dose of osimertinib until the date of objective disease progression or death (by any cause in the absence of progression).
Measured: End of study (approximately 4 years)
Duration of Response according to Response Evaluation Criteria in Solid Tumors version 1.1 in the Atypical Epidermal Growth Factor Receptor Mutation Population
Duration of Response in the atypical Epidermal Growth Factor Receptor (EGFR) population will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), in both the first line and third line settings. Duration of Response is the time from the date of first documented response until date of documented progression or death (in the absence of disease progression), in the third-line setting (osimertinib re-challenge).
Measured: End of study (approximately 4 years)
Disease Control Rate according to Response Evaluation Criteria in Solid Tumors version 1.1 in the Atypical Epidermal Growth Factor Receptor Mutation Population
Disease Control Rate in the atypical Epidermal Growth Factor Receptor (EGFR) population will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), in both the first line and third line settings. Disease Control Rate is the percentage of subjects who have a best overall response of complete response or partial response or stable disease.
Measured: End of study (approximately 4 years)
Tumor Shrinkage according to Response Evaluation Criteria in Solid Tumors version 1.1 in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time to Treatment Failure is the time from first dose of osimertinib, until the date of objective disease progression leading to the decision to proceed with the next line of systemic therapy, or permanently forego antineoplastic system therapy, or death (by any cause in the absence of progression). Time to treatment failure will be analyzed in the atypical Epidermal Growth Factor Receptor (EGFR) mutation population, in both the first line and third line settings.
Measured: End of study (approximately 4 years)
Overall Survival in the Atypical Epidermal Growth Factor Receptor Mutation Population
Overall Survival is the time from the date of the first osimertinib dose, until death due to any cause. Overall Survival will be analyzed in the atypical Epidermal Growth Factor Receptor (EGFR) mutation population, in both the first line and third line settings.
Measured: End of study (approximately 4 years)
Time to Treatment Failure in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time to Treatment Failure is the time from first dose of osimertinib, until the date of objective disease progression leading to the decision to proceed with the next line of systemic therapy, or permanently forego antineoplastic system therapy, or death (by any cause in the absence of progression). Time to Treatment Failure will be analyzed in the atypical Epidermal Growth Factor Receptor (EGFR) mutation population, in both the first line and third line settings.
Measured: End of study (approximately 4 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start6 Jan 2021
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mark Vincent
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor-investigator, Mark Vincent, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Investigators
- Mark Vincent, MD, Principal investigator, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04335292
- Sponsor's protocol ID
- OCELOT
- Acronym
- OCELOT
- Status last verified
- Oct 2024
- First submitted
- 6 Mar 2020
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Osimertinib Then Chemotherapy in EGFR-mutated Lung Cancer with Osimertinib Third-line Rechallenge
- ClinicalTrials.gov ID
- NCT04335292
- Acronym / sponsor ID
- OCELOT / OCELOT
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Epidermal Growth Factor Receptor Mutation, Advanced Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Mark VincentUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 6 Jan 2021 (actual)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 6 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II single-armed study will examine the clinical utility of retreating patients with osimertinib, in the third-line, following first-line treatment with osimertinib and second-line treatment with platinum and pemetrexed chemotherapy. The current standard of care for first-line Epidermal Growth Factor Receptor (EGFR) mutated Advanced Non-Small Cell Lung Cancer (aNSCLC) is osimertinib, followed by cytotoxic chemotherapy.
The repeat of osimertinib following previous treatment failure is investigational, although supported by scientific rationale. The dosing and scheduling of osimertinib follows its use in approved settings. The investigators examine its tolerability and efficacy in this setting to ensure osimertinib is a safe third-line option for patients with Epidermal Growth Factor Receptor mutated (EGFR+) Advanced Non-Small Cell Lung Cancer(aNSCLC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Osimertinib First-Line, Drug: Platinum + Pemetrexed Chemotherapy Second-Line, Drug: Osimertinib Third-LineFirst-line treatment = osimertinib, 80 mg, oral, daily; Second-line treatment = platinum (carboplatin or cisplatin) + pemetrexed chemotherapy, prescribed as per institutional standards; Third-line treatment = osimertinib rechallenge, 80 mg, oral, daily. Patients may enter the study at first-line treatment, second-line treatment, or third-line treatment. This is dependent on meeting the eligibility criteria. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Provision of informed consent prior to any study specific procedures
- Male or female patients of at least 18 years of age
- Pathologically proven advanced non-small cell lung cancer (i.e. stage M1 (metastasis), or earlier stages if unfit or unsuitable for radical treatment). Patients must have a tissue diagnosis of lung cancer, either by histology or cytology, however, in the event that there is insufficient tissue for molecular analysis, mutations identified in circulating tumor deoxyribonucleic acid (ctDNA) analysis will be permitted.
- Patients must have a known activating Epidermal Growth Factor Receptor (EGFR) mutation. Atypical Epidermal Growth Factor Receptor (EGRF) mutations are allowed. Atypical mutations may require sponsor approval. Exon 20 insertions will not be allowed.
- Patients must have an Eastern Cooperative Oncology Group/World Health Organisation Performance Status (ECOG/WHO-PS) of 0-3 and an expectation that they could potentially receive second-line chemotherapy
Key exclusion criteria (29 listed)
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or involved staff at the study site).
- A second invasive malignancy in the previous three years, other than localized non-melanoma skin cancer, which might be confused with the Epidermal Growth Factor Receptor (EGFR) mutated lung cancer.
- Any other serious and uncontrolled medical or psychiatric condition which would likely interfere in the conduct of the study.
- Pregnancy or lactation
- Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
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 |
|---|---|---|
| Osimertinib First-LineOsimertinib, 80 mg, oral, daily | Drug | Treatment Arm |
| Platinum + Pemetrexed Chemotherapy Second-LinePlatinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed are prescribed as per institutional standards. | Drug | Treatment Arm |
| Osimertinib Third-LineRechallenge with osimertinib, 80 mg, oral, daily | Drug | Treatment Arm |
Primary outcome
Objective Response Rate according to Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: End of study (approximately 4 years)
Objective Response Rate will be determined using investigator assessments according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Objective Response Rate is the percent of subjects with measurable disease with at least one visit response of complete response or partial response.
17 secondary outcomes
Progression Free Survival according to Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: End of study (approximately 4 years)
Duration of Response according to Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: End of study (approximately 4 years)
Disease Control Rate according to Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: End of study (approximately 4 years)
Tumor Shrinkage according to Response Evaluation Criteria in Solid Tumors version 1.1
Time frame: End of study (approximately 4 years)
Overall Survival
Time frame: End of study (approximately 4 years)
Time to Treatment Failure
Time frame: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Health Related Quality of Life Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30
Time frame: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Health Related Quality of Life Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-LC 13
Time frame: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Disease-Related Symptoms Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires EORTC QLQ-C30
Time frame: End of study (approximately 4 years)
Effect of Osimertinib Rechallenge on Disease-Related Symptoms Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-LC 13
Time frame: End of study (approximately 4 years)
Objective Response Rate in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time frame: End of study (approximately 4 years)
Progression Free Survival according to Response Evaluation Criteria in Solid Tumors in the Atypical Epidermal Growth Factor Receptor Population
Time frame: End of study (approximately 4 years)
Duration of Response according to Response Evaluation Criteria in Solid Tumors version 1.1 in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time frame: End of study (approximately 4 years)
Disease Control Rate according to Response Evaluation Criteria in Solid Tumors version 1.1 in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time frame: End of study (approximately 4 years)
Tumor Shrinkage according to Response Evaluation Criteria in Solid Tumors version 1.1 in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time frame: End of study (approximately 4 years)
Overall Survival in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time frame: End of study (approximately 4 years)
Time to Treatment Failure in the Atypical Epidermal Growth Factor Receptor Mutation Population
Time frame: End of study (approximately 4 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- Individual participant dataSharing planned: No
Related trials for Non-Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
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.
Daniel Breadner, MD contact
Mark Vincent, MD principal investigator
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Osimertinib First-Line, Platinum + Pemetrexed Chemotherapy Second-Line and Osimertinib Third-Line in people with Non-Small Cell Lung Cancer, run by Mark Vincent at 10 sites in Canada.
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 19 inclusion and 29 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: looking for participants now, as of the sponsor's last update on 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Canada. 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 phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mark Vincent, MD (519-685-8640, Mark.Vincent@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate according to Response Evaluation Criteria in Solid Tumors version 1.1 (time frame: End of study (approximately 4 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2024.