Osimertinib Then Chemotherapy in EGFR-mutated Lung Cancer with Osimertinib Third-line Rechallenge

NCT04335292 | Recruiting Phase 2 DMC

• 1 other identifier: OCELOT
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 10

Brief 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. 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

Keywords

Epidermal Growth Factor Receptor Mutation; Advanced Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  End of study (approximately 4 years)

Secondary Outcomes (17)

• Progression Free Survival according to Response Evaluation Criteria in Solid Tumors version 1.1

  End of study (approximately 4 years)

• Duration of Response according to Response Evaluation Criteria in Solid Tumors version 1.1

  End of study (approximately 4 years)

• Disease Control Rate according to Response Evaluation Criteria in Solid Tumors version 1.1

  End of study (approximately 4 years)

• Tumor Shrinkage according to Response Evaluation Criteria in Solid Tumors version 1.1

  End of study (approximately 4 years)

• Overall Survival

  End of study (approximately 4 years)

Other Outcomes (11)

• Analysis of Mutations in Circulating Tumor Deoxyribonucleic Acid Blood Samples

  End of study (approximately 4 years)

• Effects of Duration on Osimertinib on Post Progression Outcomes During First-Line Treatment

  End of study (approximately 4 years)

• Effects of Duration on Osimertinib on Post Progression Outcomes During Third-Line Treatment

  End of study (approximately 4 years)

Study Arms (1)

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.

Drug: Osimertinib First-Line; Drug: Platinum + Pemetrexed Chemotherapy Second-Line; Drug: Osimertinib Third-Line

Interventions

Osimertinib First-Line DRUG

Osimertinib, 80 mg, oral, daily

Treatment Arm

Platinum + Pemetrexed Chemotherapy Second-Line DRUG

Platinum-based chemotherapy (carboplatin or cisplatin) and pemetrexed are prescribed as per institutional standards.

Treatment Arm

Osimertinib Third-Line DRUG

Rechallenge with osimertinib, 80 mg, oral, daily

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Mark Vincent: lead
• AstraZeneca: collaborator

Study Sites (10)

BC Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Lions Gate Hospital

Vancouver, British Columbia, V7L 2L7, Canada

RECRUITING

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

RECRUITING

Hamilton Health Sciences Centre, Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

RECRUITING

London Regional Cancer Program of the Lawson Health Research Institute

London, Ontario, N6A 5W9, Canada

RECRUITING

Durham Regional Cancer Centre, Lakeridge Health

Oshawa, Ontario, L1G 2B9, Canada

RECRUITING

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Platinum

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Mark Vincent, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Vincent, MD

CONTACT

519-685-8640; Mark.Vincent@lhsc.on.ca

Daniel Breadner, MD

CONTACT

Daniel.Breadner@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: April 6, 2020
• Study Start: January 6, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10)