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Trial of Local Consolidation Therapy (LCT) After Osimertinib for Patients With EGFR Mutant Metastatic Non-Small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT03410043
Recruitment Status : Recruiting
First Posted : January 25, 2018
Last Update Posted : September 7, 2018
Sponsor:
Collaborators:
National Comprehensive Cancer Network
AstraZeneca
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this research is to learn if receiving local consolidation therapy (LCT-- surgery, radiation, or a combination of radiation and surgery) after receiving osimertinib can help to control non-small cell lung cancer (NSCLC) compared to continued treatment with osimertinib alone. The safety of this treatment will also be studied.

This is an investigational study. Osimertinib is FDA approved and commercially available for the treatment of NSCLC. It is considered investigational to give surgery and/or radiation after osimertinib to patients with NSCLC.

Up to 143 participants will be enrolled in this multicenter study. Up to 143 may take part at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Respiratory and Intrathoracic Organs Non-small Cell Lung Cancer Drug: Osimertinib Procedure: Local Consolidation Therapy (LCT) Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 143 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Local Consolidation Therapy (LCT) After Osimertinib for Patients With EGFR Mutant Metastatic Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : January 17, 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Group 1: Osimertinib + Local Consolidation Therapy (LCT)
Participants receive LCT after treatment with Osimertinib during Induction Therapy. Study doctor decides if participant has radiation alone, surgery alone, or radiation combined with surgery.
Drug: Osimertinib

Induction Therapy - Groups 1 and 2: Osimertinib 80 mg by mouth every day for about 6-12 weeks.

Group 2: Participants continue to take Osimertinib 80 mg by mouth every day.

Cycle of treatment is 4 weeks.

Other Name: AZD9291

Procedure: Local Consolidation Therapy (LCT)
Group 1: LCT after treatment with Osimertinib. Study doctor will decide if participant has radiation alone, surgery alone, or radiation combined with surgery.

Experimental: Group 2: Osimertinib
Participants continue treatment with Osimertinib after Induction Therapy.
Drug: Osimertinib

Induction Therapy - Groups 1 and 2: Osimertinib 80 mg by mouth every day for about 6-12 weeks.

Group 2: Participants continue to take Osimertinib 80 mg by mouth every day.

Cycle of treatment is 4 weeks.

Other Name: AZD9291




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: Start of induction osimertinib up to 22 months ]
    Progression-free survival (PFS) defined as the duration of time from start of induction Osimertinib to time of progression or death, whichever occurs first. Progression measured using RECIST 1.1 criteria.


Secondary Outcome Measures :
  1. Time to Appearance of New Metastases (TANM) [ Time Frame: Start of induction osimertinib to the time of development of a new lesion up to 22 months ]
  2. Progression of Target Lesions [ Time Frame: Start of induction osimertinib to the time of development of a new lesion up to 22 months ]

    Progression of target lesions defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

    Target lesions defined as those lesions treated with radiation therapy or surgery if the patient is randomized to the LCT arm of the study.


  3. Progression of Non-Target Lesions [ Time Frame: Start of induction osimertinib to the time of development of a new lesion up to 22 months ]

    Progression of non-target target lesions defined by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).

    Non-target lesions are defined as those lesions treated with radiation therapy or surgery if the patient is randomized to the LCT arm of the study.


  4. Adverse Events of Osimertinib with and without LCT [ Time Frame: Start of induction osimertinib to the time of development of a new lesion up to 22 months ]
    Safety evaluated using CTCAE v4.0 criteria, with a specific focus on ≥ Grade 3 toxicity.

  5. Overall survival (OS) [ Time Frame: Overall survival (OS) determined from start of induction Osimertinib to death up to 22 months ]
  6. Determination Whether Osimertinib plus LCT Improves Progression-Free Survival Compared with Osimertinib Alone in the Subgroup of Patients with Oligometastatic NSCLC (up to3 metastases) [ Time Frame: Induction of Osimertinib up to 22 months ]
  7. Determination Whether Osimertinib plus LCT Improves Overall Survival (OS) Compared with Osimertinib Alone [ Time Frame: Induction up to 22 months ]
  8. Determination if There is a Difference in Survival Outcomes or Toxicity by Radiation Treatment Modality (protons vs. photons) [ Time Frame: Start of radiation therapy up to 22 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >/= 18
  2. Histologically or cytologically confirmed non-small cell lung cancer
  3. Stage IIIB/IV or recurrent non-small cell lung cancer which is not amenable to curative intent therapy.
  4. Patients must have one of the following: (A) NSCLC which harbours EGFR Exon 19 deletion or L858R mutation. This subset of patients must be TKI naive; OR (B) NSCLC which harbours an EGFR T790M mutation that was acquired following progression on erlotinib, gefitinib or afatinib. This subset of patients must have not received prior third generation TKI. NOTE: EGFR mutation must be documented by a Clinical Laboratory Improvement Amendments (CLIA) certified test.
  5. Eastern Cooperative Oncology Group (ECOG) performance status </=1
  6. Measurable disease by RECIST 1.1
  7. Candidate for local consolidation therapy to at least one site of disease.
  8. Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation.
  9. Ability to take pills by mouth.
  10. Females of childbearing potential: (1) must not be breast feeding; (2) must have a negative serum or urine pregnancy test; and (3) must agree to use adequate contraception for a minimum of two weeks prior to receiving study medication until 3 months after discontinuation of the study medication. NOTE: Acceptable methods of contraception include total and true sexual abstinence, hormonal contraceptives that are not prone to drug-drug interactions (IUS Levonorgestrel Intra Uterine System (Mirena), Medroxyprogesterone injections (Depo-Provera)), copper-banded intra-uterine devices, and vasectomized partner. All hormonal methods of contraception should be used in combination with the use of a condom by their sexual male partner. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
  11. Continued from #10: Women will be considered post-menopausal if they have been amenorrheic for the past 12 months without an alternative medical cause. The following age-specific requirements must also apply: Women < 50 years old: they would be considered post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of exogenous hormonal treatments. The levels of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) must also be in the post-menopausal range (as per the institution). Women >/= 50 years old: they would be consider post-menopausal if they have been amenorrheic for the past 12 months or more following cessation of all exogenous hormonal treatments, or have had radiation-induced oophorectomy with the last menses > 1 year ago, or have had chemotherapy-induced menopause with >1 year interval since last menses, or have had surgical sterilization by either bilateral oophorectomy or hysterectomy.
  12. 10. Non-sterilized males who are sexually active with a female partner of childbearing potential must use adequate contraception for the duration of the study and 3 month after the last dose of study medication. Adequate contraception methods include: birth control pills (eg combined oral contraceptive pill), barrier protection (eg condom plus spermicide, cervical/vault cap or intrauterine device), and abstinence. Patients should not father a child for 6 months after completion of the study medication. Patients should refrain from donating sperm from the start of dosing until 6 months after discontinuing the study medication. If male patients wish to father children they should be advised to arrange for freezing of sperm samples prior to the start of the study medication.
  13. Life expectancy >=12 weeks
  14. To be eligible for randomization, patients must: (a) Meet all the inclusion criteria; (b) Have no progression of disease after 6-12 weeks of osimertinib per RECIST 1.1. (To assess for progressive disease patients must have the following imaging: 1) either a PET/CT scan or a CT scan of the chest/abdomen/pelvis (or CT chest) and 2) a CT scan or an MRI of the brain); and (c) Have target lesions (lesions that will be treated with LCT if the patient is randomized to that arm). Patients that have a CR to front-line osimertinib (e.g. no visible disease to target) will continue to be followed for progression on study but will not be randomized.

Exclusion Criteria:

  1. Previous treatment with osimertinib, or a 3rd generation EGFR TKI. NOTE: Patients who are receiving initial osimertinib (6-12 weeks) outside this study are not excluded.
  2. Patients 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 CYP3A4 (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
  3. Patients with symptomatic CNS metastases who are neurologically unstable.
  4. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.
  5. 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 subject 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.
  6. 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.
  7. 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.
  8. Patients with uncharacterized eye disorders.
  9. Males and females of reproductive potential who are not using and effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry.
  10. History of hypersensitivity of osimertinib (or active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib)
  11. 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 requirement.
  12. Inadequate bone marrow or organ function as demonstrated by any of the following laboratory values: absolute neutrophil count<1,500/mcL, platelet<100,000/mcL, hemoglobin<9.0 g/dL, total bilirubin >1.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >3 times ULN in the presence of documented Gilbert's Syndrome or liver metastases, AST(SGOT)/ALT(SGPT) >2.5 times ULN or >5 times ULN if liver metastases are present, creatinine clearance <50 mL/min/1.73 m2 by Cockcroft-Gault equation
  13. Any of the following cardiac criteria: (a) Mean resting corrected QT interval (QTc using Fridericia's formula) > 470 msec; (b) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250msec; (c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia 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.
  14. Patients will be excluded from randomization if they meet any of the following criteria: (a) Any of the exclusion criteria; (b) Complete response to osimertinib or prior treatment to all visible lesions, such that no lesion is amenable to LCT. Note that patients can receive palliative radiation therapy prior to randomization to CNS lesions or those requiring urgent treatment (e.g. for pain or bleeding), but are only eligible for the study if they have one site amenable to further radiation therapy. In addition, these lesions will be counted towards the total number of metastases, and will also be counted as target lesions.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410043


Contacts
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Contact: Daniel Gomez, MD 713-563-2300 dgomez@mdanderson.org

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Trever Bivona, MD, PhD         
United States, Colorado
University of Colorado Recruiting
Boulder, Colorado, United States, 80309
Contact: Robert Doebele, MD, PhD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63130
Contact: Ramaswamy Govindan, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       dgomez@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Comprehensive Cancer Network
AstraZeneca
Investigators
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Principal Investigator: Daniel Gomez, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03410043     History of Changes
Other Study ID Numbers: 2017-0228
NCI-2018-00937 ( Registry Identifier: NCI CTRP )
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: September 7, 2018
Last Verified: September 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant neoplasms of respiratory and intrathoracic organs
Non-small cell lung cancer
NSCLC
Osimertinib
AZD9291
Local consolidative therapy
LCT
Radiotherapy
Surgical resection

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action