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Trial record 26 of 41 for:    ALECTINIB

A Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Participants With Stages I-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, or BRAF v600E Molecular Alterations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04302025
Recruitment Status : Not yet recruiting
First Posted : March 10, 2020
Last Update Posted : March 10, 2020
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief Summary:
This trial will evaluate the efficacy and safety of targeted therapies in participants with resectable Stage IA2, IB, IIIA, or selected IIIB resectable and untreated non-small cell lung cancer (NSCLC) tumors with selected molecular alterations.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: Alectinib Drug: Entrectinib Drug: Vemurafenib Drug: Cobimetinib Procedure: Resection Radiation: Radiotherapy Drug: Chemotherapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Phase II, Neoadjuvant and Adjuvant Study of Alectinib, Entrectinib, or Vemurafenib Plus Cobimetinib in Patients With Stages I-III Non-Small Cell Lung Cancer With ALK, ROS1, NTRK, or BRAF v600E Molecular Alterations
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : February 2, 2028
Estimated Study Completion Date : February 2, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: ALK Cohort
Patients will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with alectinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
Drug: Alectinib
Participants will receive oral alectinib twice per day (BID)

Procedure: Resection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes

Radiation: Radiotherapy
Participants will receive radiotherapy as deemed appropriate by the treating physician

Drug: Chemotherapy
Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician

Experimental: ROS 1 Cohort
Patients will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with entrectinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
Drug: Entrectinib
Participants will receive oral entrectinib daily

Procedure: Resection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes

Radiation: Radiotherapy
Participants will receive radiotherapy as deemed appropriate by the treating physician

Drug: Chemotherapy
Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician

Experimental: NTRK Cohort
Patients will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with entrectinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
Drug: Entrectinib
Participants will receive oral entrectinib daily

Procedure: Resection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes

Radiation: Radiotherapy
Participants will receive radiotherapy as deemed appropriate by the treating physician

Drug: Chemotherapy
Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician

Experimental: BRAF Cohort
Patients will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per standard of care. All patients that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the Adjuvant Treatment Phase with vemurafenib plus cobimetinib. Choice of adjuvant treatment will be at the discretion of the treating physician, depending on the disease stage, as deemed clinically appropriate.
Drug: Vemurafenib
Participants will receive oral vemurafenib BID

Drug: Cobimetinib
Participants will receive oral cobimetinib daily

Procedure: Resection
Participants will receive surgical resection of the primary tumor along with selected lymph nodes

Radiation: Radiotherapy
Participants will receive radiotherapy as deemed appropriate by the treating physician

Drug: Chemotherapy
Participants will receive standard of care (SOC) chemotherapy as determined by the treating physician




Primary Outcome Measures :
  1. Proportion of Participants with Major Pathologic Response (MPR) [ Time Frame: After surgical resection (approximately study Week 8) ]
    MPR is defined as </=10% residual viable tumor cells


Secondary Outcome Measures :
  1. Pathological Regression Based on % Viable Tumor Cell Assessment [ Time Frame: After surgical resection (approximately study Week 8) ]
  2. Investigator-Assessed Response Objective Response Rate (ORR) per RECIST v1.1 [ Time Frame: After neoadjuvant treatment (after approximately study Week 8) ]
  3. Pathological Complete Response (pCR) as Assessed by Investigator Site Pathology Laboratory [ Time Frame: At the time of surgical resection (approximately study Week 8) ]
    pCR is defined as the absence of residual invasive in situ cancer and all sampled regional lymph nodes

  4. Disease-Free Survival (DFS) [ Time Frame: From the first date of no disease to local or distant recurrence or death from any cause, whichever occurs first, through the end of the study (up to 8 years) ]
  5. Event-Free Survival (EFS) [ Time Frame: From first dose of study treatment to first documented disease progression per RECIST v1.1, or local or distant disease recurrence as determined by investigator, or death from any cause, whichever occurs first, through the end of study (up to 8 years) ]
  6. Overall Survival (OS) [ Time Frame: From the first dose of study medication to death from any cause, through the end of the study (up to 8 years) ]
  7. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 8 years ]


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

Neoadjuvant Therapy:

  • Pathologically documented NSCLC
  • Molecular testing results from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories and showing at least one of the following abnormalities: ALK gene rearrangement; ROS1 gene rearrangement; NTRK1/2/3 gene rearrangement; BRAF V600 mutation
  • Molecular testing results used for patient eligibility should be obtained from the most recent tumor biopsy. Alternatively, and for patients with ALK, ROS1, and NTRK1/2/3 molecular alterations, molecular testing results used to determine patient eligibility could have been obtained from a recent blood sample (up to 2 months prior to enrollment) described in the study design
  • Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • NSCLC must have a solid or subsolid appearance on computed tomography (CT) scan and cannot have a purely ground glass opacity appearance. For sub-solid lesions, the tumor size (i.e., clinical T stage) should be measured based on the solid component only, exclusive of the ground glass opacity component
  • Evaluated by the attending surgeon prior to study enrollment to verify that the primary tumor and any involved lymph nodes are technically completely resectable and verify that the patient is medically operable
  • Adequate pulmonary function to be eligible for surgical resection with curative intent
  • Adequate cardiac function to be eligible for surgical resection with curative intent
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate hematologic and end-organ function
  • Male patients must be willing to use acceptable methods of contraception. Treatment-specific contraceptive requirements will be in the specific protocol appendix for each study drug
  • Female patients of childbearing potential must agree to use acceptable methods of contraception. For treatment-specific contraceptive requirements, please see the specific appendix for each study drug

Adjuvant Therapy:

  • Patients whose tumors have pathologic response or lack of radiographic progression
  • ECOG Performance Status of 0 or 1
  • Adequate hematologic and end-organ function

Exclusion Criteria

  • NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
  • Any prior therapy for lung cancer, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within 2 years
  • Patients with prior lung cancer that have been in remission for < 2 years with the exception of minimally invasive adenocarcinoma or incidental typical carcinoid tumors
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1
  • Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of patients with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, non-muscle invasive bladder cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per SOC management (e.g., Rai Stage 0 chronic lymphocytic leukemia, prostate cancer with Gleason score </= 6, and prostate-specific antigen (</= 10 ng/mL, etc.)
  • Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1 (or within 5 half-lives of the investigational product, whichever is longer)
  • Known HIV positivity or AIDS-related illness
  • Pregnant or lactating, or intending to become pregnant during the study

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): NCT04302025


Contacts
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Contact: Reference Study ID Number: ML41591 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 global-roche-genentech-trials@gene.com

Sponsors and Collaborators
Genentech, Inc.
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT04302025    
Other Study ID Numbers: ML41591
First Posted: March 10, 2020    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com).

Further details on Roche's criteria for eligible studies are available here: https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here: (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Vemurafenib
Entrectinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action