Chemotherapy Combined With Immunotherapy vs Immunotherapy Alone for Older Adults With Stage IIIB-IV Lung Cancer, The ACHIEVE Trial
Purpose
This phase III trial compares the effect of adding chemotherapy to immunotherapy (pembrolizumab) versus immunotherapy alone in treating patients with stage IIIB-IV lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab and chemotherapy may help stabilize lung cancer.
Conditions
- Advanced Lung Non-Small Cell Carcinoma
- Stage IIIB Lung Cancer AJCC v8
- Stage IIIC Lung Cancer AJCC v8
- Stage IV Lung Cancer AJCC v8
Eligibility
- Eligible Ages
- Over 70 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- STEP 1 REGISTRATION
- Patient must be ≥ 70 years of age
- Patient must have histologically or cytologically confirmed non-small cell lung cancer
(NSCLC) with PD-L1 Tumor Proportion Score (TPS) range of 1-49%
- Patient must have Stage IIIB, IIIC or IV disease and not be candidates for combined
chemo-radiation. NOTE: Prior chemo-radiation therapy (RT) for stage III with
recurrence is allowed
- Patient must have a tumor that is negative for EGFR mutation/ALK translocations or
other actionable first line mutations in which patients would receive first-line oral
tyrosine kinase inhibitors
- Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2
- Patient must agree not to father children while on study and for 6 months after the
last dose of protocol treatment
- Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC) who
have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
- Absolute neutrophil count (ANC) ≥ 1,500/mcL (obtained within 14 days prior to Step 1
registration)
- Platelets ≥ 75,000/mcL (obtained within 14 days prior to Step 1 registration)
- Hemoglobin (Hgb) ≥ 8.0 g/dL (obtained within 14 days prior to Step 1 registration)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained within 14
days prior to Step 1 registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
≤ 3.0 × institutional ULN (obtained within 14 days prior to Step 1 registration)
- Creatinine clearance (CrCL) ≥ 45 mL/min (estimated using Cockcroft-Gault method with
actual body weight or measured) (obtained within 14 days prior to Step 1 registration)
- Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral
therapy with undetectable viral load within 6 months of Step 1 registration are
eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have undetectable HCV viral
- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial
- Patient must be English or Spanish speaking to be eligible for the QOL component of
the study
- NOTE: Sites cannot translate the associated QOL forms
- Patient must not have symptomatic central nervous system disease (CNS) metastases.
Patients with a clinical history of CNS metastases or cord compression are eligible if
they have been definitively treated and are clinically stable for at least 14 days
prior to Step 1 registration and off all steroids for at least 24 hours prior to Step
1 registration. Patients with asymptomatic CNS metastases are eligible
- Patient must not have had any prior cytotoxic chemotherapy regimen for metastatic
disease. Chemotherapy given in the setting of adjuvant therapy or locally advanced
disease is allowed as long as treatment was completed, and they have fully recovered
from treatment related adverse events prior to Step 1 registration
- Patient must not have had any prior immunotherapy for metastatic disease.
Immunotherapy given in the setting of adjuvant therapy or locally advanced disease is
allowed as long as treatment was completed greater than 6 months prior to Step 1
registration
- Patient must not have a history of uncontrolled autoimmune conditions with the
following exceptions, which are allowed: alopecia, vitiligo, rheumatoid arthritis,
psoriasis/psoriatic arthritis, Hashimoto's thyroiditis, lupus, inflammatory bowel
disease
- Patient must not be on immunosuppressive medication, including steroids (if doses
exceed the equivalent of prednisone 10 mg daily). Short courses of steroids which are
discontinued prior to randomization are acceptable. Patients on inhaled, intranasal
and/or topical steroids are eligible
- Investigator must declare their intended chemotherapy regimen should their patient be
randomized to Arm B (doublet vs singlet)
- STEP 2 RANDOMIZATION
- Patient must have completed the baseline Geriatric Assessment (GA) after Step 1
registration and prior to Step 2 randomization
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Arm A (pembrolizumab) |
INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI at baseline and CT and/or PET on the trial at baseline and throughout the trial. Patients may also undergo stool sample collection at baseline and on the trial. |
|
|
Experimental Arm B (pembrolizumab, chemotherapy) |
See Detailed Description |
|
Recruiting Locations
Cleveland, Ohio 44109
More Details
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Study Contact
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate whether there is an improvement in overall survival (OS) with chemotherapy combined with pembrolizumab compared to single agent pembrolizumab in this vulnerable older adult patient population. SECONDARY OBJECTIVES: I. To evaluate any difference in progression free survival (PFS) with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab. II. To evaluate the difference in PFS rate at 3 months and at 6 months with chemotherapy combined with pembrolizumab as compared to single agent pembrolizumab. III. To evaluate the difference in best objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria to assess whether chemotherapy combined with pembrolizumab results in improved response rates compared to treatment with single agent pembrolizumab. IV. To evaluate toxicity in those treated with chemotherapy combined with pembrolizumab compared to those treated with single agent pembrolizumab. V. To evaluate patient reported quality of life (QOL) evaluations between treatment arms. EXPLORATORY OBJECTIVES: I. To compare safety and tolerability between treatment arms including but not limited to number of additional lab draws, scan appointments, infusion visits, falls, emergency department visits, and hospitalization related to treatment toxicity. II. To explore factors within the pre-treatment geriatric assessment (GA) as predictors of toxicity and outcomes. To describe changes between the intended chemotherapy treatment planned versus treatment given and referrals placed by treating provider based on GA results. III. To evaluate the assessment of a novel, composite fPFS score using disease progression/functional impairment assessment as a potential correlate to OS in this vulnerable population. IV. To evaluate the correlation of 3-months PFS with OS as a potential surrogate of OS benefit. V. To evaluate the correlation of 6-months PFS with OS as a potential surrogate of OS benefit. VI. To assess elective dose intensity of chemotherapy of patients who receive doublet chemotherapy versus single agent chemotherapy. EXPLORATORY CORRELATIVE OBJECTIVE: I. To relate gut microbe abundances to treatment outcomes, toxicity, and geriatric assessments. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: INDUCTION: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM B: INDUCTION: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive investigator's choice of a chemotherapy regimen: 1) Pemetrexed IV over 10 minutes + carboplatin IV over 30-60 minutes on day 1 of each cycle; 2) Nab-paclitaxel IV over 30 on days 1, 8, and 15 of each cycle + carboplatin IV over 30-60 minutes on day 1 of each cycle; 3) Paclitaxel IV over 1 hour on day 1, 8, and 15 of each cycle or over 3 hours on day 1 of each cycle + carboplatin IV over 30-60 minutes on day 1 of each cycle; 4) Nab-paclitaxel IV over 30 minutes on days 1, 8 and 15 of each cycle; 5) Paclitaxel IV over 3 hours on day 1 of each cycle or over 1 hour on days 1, 8, and 15 of each cycle; or 6) Pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 or 42 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients undergo magnetic resonance imaging (MRI) at baseline and computed tomography (CT) and/or positron emission tomography (PET) on the trial at baseline and throughout the trial. Patients may also undergo stool sample collection at baseline and on the trial. After completion of study treatment, patients are followed up every 3 months if < 2 years from randomization and every 6 months if 2-5 years from Step 1 registration.