Current Clinical Trials

E4512: Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)
  1. Davood Vafai, MD
    Davood Vafai, MD
  2. for people 18 Years and up (full criteria)
  3. Rancho Mirage, CA
  4. study started June 2017
  5. Davood Vafai, MD
  6. Accepting new patients

Description

Summary

This randomized phase III trial studies how well crizotinib works and compares it to placebo in treating patients with stage IB-IIIA non-small cell lung cancer that has been removed by surgery and has a mutation in a protein called anaplastic lymphoma kinase (ALK). Mutations, or changes, in ALK can make it very active and important for tumor cell growth and progression. Crizotinib may stop the growth of tumor cells by blocking the ALK protein from working. Crizotinib may be an effective treatment for patients with non-small cell lung cancer and an ALK fusion mutation.

Official Title

E4512: A Randomized Phase III Trial for Surgically Resected Early Stage Non-small Cell Lung Cancer: Crizotinib Versus Observation for Patients With Tumors Harboring the Anaplastic Lymphoma Kinase (ALK) Fusion Protein (An ALCHEMIST Treatment Trial)

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) for patients with stage IB >= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection. SECONDARY OBJECTIVES: I. To evaluate and compare disease-free survival (DFS) associated with crizotinib. II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting. III. To collect tumor tissue and blood specimens f... more
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PRIMARY OBJECTIVES: I. To evaluate whether adjuvant therapy with crizotinib will result in improved overall survival (OS) for patients with stage IB >= 4 cm, II and IIIA, ALK-positive non-small cell lung cancer (NSCLC) following surgical resection. SECONDARY OBJECTIVES: I. To evaluate and compare disease-free survival (DFS) associated with crizotinib. II. To evaluate the safety profile of crizotinib when given in the adjuvant therapy setting. III. To collect tumor tissue and blood specimens for future research. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive crizotinib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients undergo observation. After completion of study treatment, patients are followed up every 6 months if < 4 or 5 years from study entry, and every 12 months if 5-10 or 6-10 years from study entry.

Keywords

NSCLC with ALK Gene Rearrangement

Eligibility

for people 18 Years and up
Inclusion Criteria: Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II, or non-squamous IIIA NSCLC per American Joint Committee on Cancer (AJCC) 7th edition and have had negative margins; N3 disease is not allowed Baseline chest computed tomography (CT) with or without contrast must be performed within 6 months (180 days) prior to randomization to ensure no evidence of disease; if clinically indicated additional imaging studies must be performed to rule o... more
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Inclusion Criteria: Patients must have undergone complete surgical resection of their stage IB (>= 4 cm), II, or non-squamous IIIA NSCLC per American Joint Committee on Cancer (AJCC) 7th edition and have had negative margins; N3 disease is not allowed Baseline chest computed tomography (CT) with or without contrast must be performed within 6 months (180 days) prior to randomization to ensure no evidence of disease; if clinically indicated additional imaging studies must be performed to rule out metastatic disease Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Patients must be registered to the ALCHEMIST-SCREEN (ALLIANCE A151216) trial prior to randomization Positive for translocation or inversion events involving the ALK gene locus (e.g. resulting in echinoderm microtubule associated protein like 4 [EML4]-ALK fusion) as determined by the Vysis Break Point fluorescence in situ hybridization (FISH) assay and defined by an increase in the distance between 5? and 3? ALK probes or the loss of the 5? probe; this must have been performed: By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory: report must indicate the results as well as the CLIA number of the laboratory which performed the assay; tissue must be available for submission for central, retrospective confirmation of the ALK fusion status via ALCHEMIST-SCREEN (ALLIANCE A151216) OR Patient registered to and the ALK fusion status performed centrally on the ALCHEMIST-SCREEN (ALLIANCE A151216) Women must not be pregnant or breast-feeding All females of childbearing potential must have a blood or urine pregnancy test within 72 hours prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Women of childbearing potential and sexually active males must be strongly advised to practice abstinence or use an accepted and effective method of contraception Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements No known interstitial fibrosis or interstitial lung disease No prior treatment with crizotinib or another ALK inhibitor No ongoing cardiac dysrhythmias of grade >= 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, uncontrolled atrial fibrillation (any grade), or corrected QT (QTc) interval > 470 msec No use of medications, herbals, or foods that are known potent cytochrome P450, subfamily 3A, polypeptide 4 (CYP3A4) inhibitors or inducers, included but not limited to those outlined Patients must be adequately recovered from surgery at the time of randomization The minimum time requirement between date of surgery and randomization must be at least 4 weeks (28 days) The maximum time requirement between surgery and randomization must be: 3 months (90 days) if no adjuvant chemotherapy was administered 8 months (240 days) if adjuvant chemotherapy was administered 10 months (300 days) if adjuvant chemotherapy and radiation therapy were administered Patients must have completed any prior adjuvant chemotherapy or radiation therapy 2 or more weeks (6 or more weeks for mitomycin and nitrosoureas) prior to randomization and be adequately recovered at the time of randomization NOTE: Patients taking low dose methotrexate for non-malignant conditions and other cytotoxic agents for non-malignant conditions are allowed to continue treatment while on study NOTE: Neo-adjuvant chemotherapy or radiation therapy for the resected lung cancer is not permitted Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) Total serum bilirubin =< 1.5 x ULN Absolute neutrophil count (ANC) >= 1500/mm^3 Platelets >= 30,000/mm^3 Hemoglobin >= 8.0 g/dL Serum creatinine =< 2 x ULN Prior to randomization patients with any non-hematologic toxicity from surgery, chemotherapy, or radiation must have recovered to grade =< 1 with the exception of alopecia and the criteria outlined Patients must not have any history of locally advanced or metastatic cancer requiring systemic therapy within 5 years from randomization, with the exception of in-situ carcinomas and non-melanoma skin cancer; patients must have no previous primary lung cancer diagnosed concurrently or within the past 2 years Patients may not be receiving any other investigational agents while on study

Lead Scientists at Eisenhower Health

Davood Vafai, MD
Board Certified in Internal Medicine and Medical Oncology, Dr. Vafai is a graduate of the Tehran Medical School in Iran. After medical school, Dr. Vafai completed his internship at Englewood Hospital in New Jersey, and a residency and oncology fellowship at the University of Southern California. He completed another fellowship in hematology and bone marrow transplantation at the University of California, San Diego.“My father had cancer, as did other family mem... more
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Board Certified in Internal Medicine and Medical Oncology, Dr. Vafai is a graduate of the Tehran Medical School in Iran. After medical school, Dr. Vafai completed his internship at Englewood Hospital in New Jersey, and a residency and oncology fellowship at the University of Southern California. He completed another fellowship in hematology and bone marrow transplantation at the University of California, San Diego.

“My father had cancer, as did other family members,” says Davood Vafai, MD, a Board Certified Medical Oncologist with Eisenhower Hematology/Oncologist Specialists. “I saw what this disease does and how it progresses, so I decided to pursue oncology as a career. It became a personal and professional challenge.”

In his current practice, Dr. Vafai sees a broad range of hematology and oncology patients; his professional interests focus on lung cancer and blood cancers such as lymphoma, leukemia and multiple myeloma. “One of the reasons for my fellowship in bone marrow transplantation is that these types of patients need a great deal of care, and I wanted to be involved,” explains Dr. Vafai.

He is the author of several publications and book chapters in addition to being Sub-investigator or pincipal Investigator for 120 oncologic treatment protocols and new drug investigations. He is an active participant on the Eisenhower Medical Center Tumor Board, and runs the Hematology/Oncology Journal Club on campus. He loves teaching and is passionate about the advances in oncology that have extended quality months of life in patients living with malignancies.

As the engineer of the lung cancer chemotherapy regimen Carboplatin and Taxol, Dr. Vafai presented this treatment at the American Society of Clinical Oncology in 1995. Since then, the Carboplatin and Taxol treatment has been a standard in lung cancer treatment in United States and across the globe. It is now being used in the treatment of many other cancers.

Additionally, Dr. Vafai is the principal investigator of the International Early Lung Cancer Action Project (I-ELCAP) at Eisenhower Medical Center which he has led for more than a decade. This modality of detection and treatment was just recently approved by United States Task Force, and is now considered a standard of treatment in the United States.

Dr. Vafai marvels at the tremendous advances in cancer treatment that have developed in years since he’s been in practice. “Oncology is probably the most complex and fastest-growing field in medicine,” he comments. “It gives patients and doctors a lot of hope.”

Clinical Study Details

  1. Accepting new patients
  2. study started June 2017
  3. Interventional
  4. April 04, 2024