Current Clinical Trials

Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)
  1. Davood Vafai, MD
    Davood Vafai, MD
  2. for people 18 Years and up (full criteria)
  3. Rancho Mirage, CA
  4. study started August 2014
  5. Davood Vafai, MD
  6. Accepting new patients

Description

Summary

This ALCHEMIST trial studies genetic testing in screening patients with stage IB-IIIA non-small cell lung cancer that has been or will be removed by surgery. Studying the genes in a patient's tumor cells may help doctors select the best treatment for patients that have certain genetic changes.

Official Title

ALCHEMIST: Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer (NSCLC) That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial). Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial

Detailed Description

PRIMARY OBJECTIVES: I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to facilitate accrual to randomized adjuvant studies. II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics ... more
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PRIMARY OBJECTIVES:

  1. I. To centrally test resected non-small cell lung cancer (NSCLC) for genetic mutations to facilitate accrual to randomized adjuvant studies.
  2. II. To obtain clinically annotated tumor tissue and patient-matched non-malignant deoxyribonucleic acid (DNA) from peripheral blood, as well as detailed epidemiologic and clinical follow-up data, to allow clinically annotated advanced genomic analyses in concert with the National Cancer Institute (NCI) Center for Cancer Genomics (CCG).

SECONDARY OBJECTIVES:

  1. I. To characterize the natural history of molecularly characterized NSCLC to allow subsequent development of targeted therapies against genotype-defined subpopulations in the adjuvant and recurrent settings.
  2. II. To cross-validate local genotyping assays for epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) with a central reference standard.

EXPLORATORY/OTHER OBJECTIVES:

  1. I. To study the genomic evolution of lung cancers by comparing genomic characteristics at resection and at recurrence.
  2. II. To understand reasons behind lack of enrollment to adjuvant targeted therapy studies for potentially eligible patients.
  3. III. To study the clinical significance of circulating tumor DNA within the plasma cell-free DNA (cfDNA) from early stage lung cancer patients.

OUTLINE:

  1. STEP 1 (SCREENING): Patients undergo collection of blood and tissue samples for EGFR, ALK, and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)/cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) testing via direct sequencing, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). Patients that have had surgery prior to pre-registration will submit samples from the previous surgery for testing.
  2. STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational drugs used in this study or those without mutations are assigned to 1 of 4 treatment subprotocols.

A081105: Patients are randomized to 1 of 4 treatment arms.

  1. ARM A (BLINDED ERLOTINIB- CLOSED 06/14/17): Blinded patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  2. ARM B (PLACEBO- CLOSED 06/14/17): Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  3. ARM C (UNBLINDED ERLOTINIB): Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  4. ARM D (OBSERVATION): Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.

E4512: Patients are randomized to 1 of 2 treatment arms.

  1. ARM A: Patients receive crizotinib 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.
  2. ARM B: Patients undergo observation. EA5142: Patients are randomized to 1 of 2 arms
    1. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or positron emission tomography (PET)/CT throughout the trial and blood samples collection during screening and follow-up.
    2. ARM II: Patients are followed serially with CT and/or PET/CT imaging for up to 1 year. Patients also undergo blood sample collection during screening and follow-up.

A081801: Patients are randomized to 1 of 3 arms.

  1. ARM A: INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then undergo observation.
  2. ARM B: INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. CONTINUANCE THERAPY: Patients then receive pembrolizumab intravenously (IV) over 25-40 minutes on day 1. Treatment repeats every 21 days for 17 cycles in the absence of disease progression or unacceptable toxicity.
  3. ARM C: INITIAL THERAPY: Patients receive 1 of 4 platinum doublet regimens* based on the treating physician's choice and pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

CONTINUANCE THERAPY:

Patients then receive pembrolizumab IV over 25-40 minutes on day 1. Treatment repeats every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity.

*ACCEPTABLE REGIMENS:

  1. DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed IV over 10 minutes on day 1 of each cycle.
  2. DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1 of each cycle.
  3. DOUBLET III: Patients receive cisplatin IV over 1-2 hours on day 1 of each cycle and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 of each cycle.
  4. DOUBLET IV: Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 1 of each cycle. After completion of study, patients that are not enrolled on either A081105, E4512, EA5142, or A081801 are followed up every 6 months for 5 years.

Keywords

Lung Adenocarcinoma

Eligibility

for people 18 Years and up
Inclusion Criteria: PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA: For pre-surgical patients Suspected diagnosis of resectable non-small cell lung cancer; cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology; patients with squamous cell carcinoma are eligible Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; ... more
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Inclusion Criteria:

PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:

  • For pre-surgical patients
    • Suspected diagnosis of resectable non-small cell lung cancer; cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology; patients with squamous cell carcinoma are eligible
    • Suspected clinical stage of IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized
  • For post-surgical patients
    • Completely resected non-small cell lung cancer with negative margins (R0); patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
    • Pathologic stage IIIA, II (IIA or IIB) or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
  • No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 year prior to registration
  • No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and PD-1/PD-L1/CTLA-4
  • No patients known to be pregnant or lactating
  • Patients who have had local genotyping are eligible, regardless of the local result
  • No patients with recurrence of lung cancer after prior resection Note: Post-surgical patients should proceed to registration immediately following preregistration

PATIENT REGISTRATION ELIGIBILITY CRITERIA:

  • Tissue available for the required analyses (either clinical tissue block or slides and scrolls)
  • Completely resected NSCLC with negative margins (R0); cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus a "nonsquamous" histology
  • Pathologic stage IIIA, IIA or IIB, or large IB (defined as size >= 4 cm); Note: IB tumors < 4 cm are NOT eligible; stage IB cancer based on pleural invasion is not eligible unless the tumor size is >= 4 cm; the 7th edition of AJCC staging will be utilized
  • Patients with squamous cell carcinoma are eligible only if they have not received adjuvant therapy
  • In order to allow for time for central genotyping and eligibility for the ALCHEMIST treatment trial, patients must register within the following eligibility windows:
    • Squamous patients:
      No adjuvant therapy permitted, register patient within 77 days following surgery
    • Non-squamous patients:
      If no adjuvant therapy, register patient within 75 days following surgery If adjuvant chemotherapy or radiotherapy only, register patient within 225 days following surgery If adjuvant chemotherapy and radiation, register patient within 285 days following surgery

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 August 2014
  3. Interventional
  4. Expecting 8300 study participants
  5. April 04, 2024