Current Clinical Trials

Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-Small Cell Lung Cancer (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 August 2021
  5. Davood Vafai, MD
  6. Accepting new patients

Description

Summary

This phase III ALCHEMIST trial compares the addition of pembrolizumab to usual chemotherapy versus usual chemotherapy for the treatment of stage IB, II, or IIIA non-small cell lung cancer that has been removed by surgery.

Official Title

A081801:Integration of Immunotherapy into Adjuvant Therapy for Resected Non-Small Cell Lung Cancer (NSCLC). An ALCHEMIST Treatment Trial/ALCHEMIST CHEMO-IO.

Detailed Description

PRIMARY OBJECTIVE: I. To compare the disease free survival (DFS) between Arm B versus (vs) Arm C in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. SECONDARY OBJECTIVES: I. To compare the overall survival (OS) between the two treatment arms in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. II. To compare the adverse event rates and drug discontinuation rates due to adverse events in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. III. To com... more
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PRIMARY OBJECTIVE: I. To compare the disease free survival (DFS) between Arm B versus (vs) Arm C in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. SECONDARY OBJECTIVES: I. To compare the overall survival (OS) between the two treatment arms in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. II. To compare the adverse event rates and drug discontinuation rates due to adverse events in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. III. To compare the adverse event (AE) rates for Arms B and C with A (prior to Update #7) and estimate the DFS and OS in Arm A. IV. To compare the DFS and OS in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer that receive at least 2 cycles of initial adjuvant chemotherapy. QUALITY OF LIFE OBJECTIVES: I. To compare patient-reported quality of life (QOL) one year after randomization as assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core (C)30 between patients randomized to receive adjuvant chemotherapy followed by pembrolizumab (Arm B), and those randomized to receive adjuvant chemotherapy + pembrolizumab concomitantly (Arm C). II. To compare patient-reported QOL at completion of chemotherapy as assessed by the EORTC QLQ-C30 between patients randomized to receive adjuvant chemotherapy followed by pembrolizumab (Arm B) and those randomized to receive adjuvant chemotherapy + pembrolizumab concomitantly (Arm C). III. To present longitudinal trajectories by arm of patient-reported dyspnea and coughing as assessed by the EORTC QLQ-Lung Cancer (LC13). CORRELATIVE SCIENCE OBJECTIVES: I. To compare the DFS and OS in the PD-L1 subgroup of patients with PD-L1 expression status (>= 1% vs < 1%). II. To compare the DFS and OS by tumor mutational burden status (high vs. low) in patients with stage IIA-IIIB (T3-4N2) non-small cell lung cancer. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A (CLOSED AS OF UPDATE #7): 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. 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 or every 6 weeks for 16 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity. 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 or every 6 weeks for 12 cycles (patients enrolled after 10/14/2020) in the absence of disease progression or unacceptable toxicity. *ACCEPTABLE REGIMENS: DOUBLET I: Patients receive cisplatin IV over 1-2 hours and pemetrexed IV over 10 minutes on day 1 of each cycle. DOUBLET II: Patients receive carboplatin IV over 30 minutes and pemetrexed IV over 10 minutes on day 1 of each cycle. 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. 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 treatment, patients are followed up at 6 weeks, then every 3 months for 2 years from randomization, every 6 months for years 2-4, and then annually for up to 10 years from randomization.

Keywords

Lung Non-Small Cell Carcinoma

Eligibility

for people 18 Years and up
Inclusion Criteria: Previously registered to A151216 (NCT02194738) Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only) Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only) Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263 Note: Local testi... more
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Inclusion Criteria: Previously registered to A151216 (NCT02194738) Central and/or local testing of EGFR with no EGFR exon 19 deletion or EGFR L858 R mutation (applicable to non-squamous patients only) Central and/or local testing of ALK with no ALK rearrangement (failed testing is considered negative) (applicable to non-squamous patients only) Central and/or local testing of PD-L1 immunohistochemistry (IHC) using one of the following assays: DAKO 22C3, DAKO 28-8, EIL3N or SP263 Note: Local testing results of EGFR and ALK by a local Clinical Laboratory Improvement Act (CLIA) certified laboratory is acceptable. The report must indicate the result as well as the CLIA number of the laboratory that performed the assay. Local result of PD-L1 by DAKO 22C3, Dako 28-8, EIL3N or SP263 are acceptable for enrollment on A081801. Patients with local results for EGFR, ALK and PD-L1 still need to be registered to A151216 and follow all the submissions requirements but do NOT need to wait for the results to proceed to A081801 registration Completely resected stage IIA, IIB IIIA or IIIB (T3-4N2) non-small cell lung cancer (NSCLC) (squamous or non-squamous) with negative margins (complete R0 resection). Patients will be staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual, 2017 Note: Patients with pathologic N2 disease, completely resected, are eligible. However, patients known to have N2 disease prior to surgery are not eligible; guidelines do not recommend up-front surgery for this population Complete recovery from surgery. Registration to A081801 must be 30-77 days following surgery No prior neoadjuvant or adjuvant therapy for current lung cancer diagnosis No prior allogeneic tissue/solid organ transplant No current pneumonitis or history of (non-infectious) pneumonitis that required steroids Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial Age >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-1 No active auto-immune disease that has required systemic treatment within the last 2 years (e.g., disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 3 years. Participants with non-melanoma skin cancers or carcinoma in situ (e.g., breast carcinoma or cervical cancer in situ) that have undergone potentially curative therapy are eligible No hypersensitivity (>= grade 3) to pembrolizumab and/or any of its excipients No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection Absolute neutrophil count (ANC) >= 1,500/mm^3 Platelet count >= 100,000/mm^3 Hemoglobin >= 8 gm/dl Calculated (Calc.) creatinine clearance >= 45 mL/min Total bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) Exclusion Criteria: Patients must NOT have uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements

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 2021
  3. Interventional
  4. April 04, 2024