Clinical Trials /

Platinum-Based Chemotherapy and Durvalumab for the Treatment of Stage IIIB or IV Non-small Cell Lung Cancer

NCT04262869

Description:

This phase II trial studies how well platinum-based chemotherapy works when given together with durvalumab in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and pemetrexed, 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. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to find out if the combination of chemotherapy in combination with the immune therapy drug durvalumab would be efficacious and have an acceptable toxicity profile in patients with advanced non-small cell lung cancer.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Squamous Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Platinum-Based Chemotherapy and Durvalumab for the Treatment of Stage IIIB or IV Non-small Cell Lung Cancer
  • Official Title: Phase 2 Study of Platinum-Based Chemotherapy in Combination With Durvalumab (MEDI 4736) for NSCLC in Patients With a Poor Performance Status and the Elderly

Clinical Trial IDs

  • ORG STUDY ID: IRB0011407
  • SECONDARY ID: NCI-2019-06508
  • SECONDARY ID: Winship4802-19
  • SECONDARY ID: P30CA138292
  • NCT ID: NCT04262869

Conditions

  • Lung Non-Small Cell Carcinoma
  • Stage IIIB Lung Cancer AJCC v8
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboArm I (squamous NSCLC)
DurvalumabImfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736Arm I (squamous NSCLC)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm I (squamous NSCLC)
PemetrexedMTA, Multitargeted AntifolateArm II (non-squamous NSCLC)

Purpose

This phase II trial studies how well platinum-based chemotherapy works when given together with durvalumab in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and pemetrexed, 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. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The purpose of this study is to find out if the combination of chemotherapy in combination with the immune therapy drug durvalumab would be efficacious and have an acceptable toxicity profile in patients with advanced non-small cell lung cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the 6-months progression-free survival (PFS) rate with the combination of
      dose attenuated doublet chemotherapy with durvalumab in advanced non-small cell lung cancer
      (NSCLC) patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2
      status or age >= 70.

      SECONDARY OBJECTIVES:

      I. To investigate overall response rate. II. To determine the safety profile of the regimen.
      III. To determine the median PFS and overall survival.

      EXPLORATORY OBJECTIVE:

      I. Exploratory investigation of biomarkers that could potentially serve as predictive
      indicators: characterize immunoprofile in peripheral blood by flow cytometry.

      OUTLINE: Patients are assigned to 1 of 2 arms.

      ARM I (SQUAMOUS NSCLC): Patients receive carboplatin intravenously (IV) over 15-60 minutes,
      paclitaxel IV over 3 hours and durvalumab IV over 1 hour on day 1. Treatment repeats every 3
      weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
      Patients who do not progress receive durvalumab IV every 4 weeks for up to 35 cycles in the
      absence of disease progression or unacceptable toxicity.

      ARM II (NON-SQUAMOUS NSCLC): Patients receive carboplatin IV over 15-60 minutes, pemetrexed
      IV over 10 minutes and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks
      for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients
      who do not progress receive durvalumab IV and pemetrexed IV every 3 weeks for up to 35 cycles
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (squamous NSCLC)ExperimentalPatients receive carboplatin IV over 15-60 minutes, paclitaxel IV over 3 hours and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not progress receive durvalumab IV every 4 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Durvalumab
  • Paclitaxel
Arm II (non-squamous NSCLC)ExperimentalPatients receive carboplatin IV over 15-60 minutes, pemetrexed IV over 10 minutes and durvalumab IV over 1 hour on day 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who do not progress receive durvalumab IV and pemetrexed IV every 3 weeks for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
  • Carboplatin
  • Durvalumab
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol

          -  Have a histologically confirmed or cytologically confirmed diagnosis of stage IIIB or
             stage IV NSCLC

          -  Have a performance status of 2 on the Eastern Cooperative Oncology Group (ECOG)
             performance status with any age, or age >= 70 with ECOG PS of 0, 1, or 2, on the day
             of signing informed consent

          -  Patients must have measurable disease based on Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1 as determined by local site investigator/radiology assessment.
             Target lesions situated in previously irradiated area are considered measurable if
             progression has been demonstrated in such lesions

          -  Have not received prior systemic treatment for their advanced/metastatic NSCLC.
             Subjects who received adjuvant or neoadjuvant therapy are eligible if the
             adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development
             of metastatic disease

          -  Body weight > 30 kg

          -  Hemoglobin >= 9.0 g/dL

          -  Absolute neutrophil count (ANC) >= 1.5 (>= 1500 per mm^3)

          -  Platelet count >= 100) x 10^9/L (>= 100,000 per mm^3)

          -  Serum bilirubin =< 1.5 x institutional upper limit of normal (ULN). (This will not
             apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
             hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
             hepatic pathology), who will be allowed if =< 3.0 x institutional upper limit of
             normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal unless liver metastases are present, in
             which case it must be =< 5 x ULN

          -  Measured creatinine clearance (CL) > 40 mL/min or calculated creatinine CL > 40 mL/min
             by the Cockcroft-Gault formula (Cockcroft and Gault 1976)

          -  The effects of the study drug on the developing human fetus are unknown. For this
             reason female of child-bearing potential (FCBP) must have a negative serum or urine
             pregnancy test prior to starting therapy

          -  FCBP and men must agree to use adequate contraception (at least one highly effective
             method and one additional method of birth control at the same time or complete
             abstinence) prior to study entry, for the duration of study participation and for at
             least 4 months following study drug discontinuation. Should a woman become pregnant or
             suspect she is pregnant while she or her partner is participating in this study, she
             should inform her treating physician immediately. A female of childbearing potential
             (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or
             bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12
             consecutive months (if age > 55 years); if the female subject is < 55 years and she
             has been naturally postmenopausal for > 1 year her reproductive status has to be
             verified by additional lab tests (< 20 estradiol OR estradiol < 40 with follicle
             stimulating hormone [FSH] > 40 in women not on estrogen replacement therapy)

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up

        Exclusion Criteria:

          -  Participation in another clinical study with an investigational product during the
             last 4 weeks

          -  ECOG PS 3 or higher

          -  Prior systemic therapy for the treatment of advanced or metastatic NSCLC

          -  Concurrent enrollment in another clinical study, unless it is an observational
             (non-interventional) clinical study or during the follow-up period of an
             interventional study

          -  Completed palliative radiotherapy within 7 days of the first dose of trial treatment

          -  Has a known sensitivity to any component of carboplatin, pemetrexed, paclitaxel, or
             durvalumab

          -  Is unable to unwilling to take folic acid of vitamin b12 supplementation (if
             non-squamous histology)

          -  Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria
             for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the
             exception of vitiligo, and the laboratory values defined in the inclusion criteria

          -  Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after
             consultation with the study physician

          -  Patients with irreversible toxicity not reasonably expected to be exacerbated by
             treatment with durvalumab may be included only after consultation with the study
             physician

          -  Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal
             therapy for cancer treatment. Concurrent use of hormonal therapy for
             non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable

          -  Major surgical procedure (as defined by the Investigator) within 28 days prior to the
             first dose of IP. Note: Local surgery of isolated lesions for palliative intent is
             acceptable

          -  History of allogenic organ transplantation

          -  Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with
             the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this
             criterion:

               -  Patients with vitiligo

               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               -  Any chronic skin condition that does not require systemic therapy

               -  Patients without active disease in the last 5 years may be included but only
                  after consultation with the study physician

               -  Patients with celiac disease controlled by diet alone

          -  Uncontrolled intercurrent illness, including but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
             gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
             situations that would limit compliance with study requirement, substantially increase
             risk of incurring adverse events (AEs) or compromise the ability of the patient to
             give written informed consent

          -  Prior invasive malignancy (except non-melanomatous skin cancer, low or intermediate
             risk prostate cancer, or in situ carcinoma fully resected) unless disease free for a
             minimum of one year

          -  History of leptomeningeal carcinomatosis

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are clinically stable for at least 2 weeks. Subjects with asymptomatic brain
             metastases may participate, but will require regular imaging of the brain as a site of
             disease

          -  History of active primary immunodeficiency

          -  Active infection including tuberculosis (clinical evaluation that includes clinical
             history, physical examination and radiographic findings, and tuberculosis [TB] testing
             in line with local practice), hepatitis B (known positive hepatitis B virus [HBV]
             surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus
             (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
             as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
             eligible. Patients positive for 20. Active infection including tuberculosis (clinical
             evaluation that includes clinical history, physical examination and radiographic
             findings, and TB testing in line with local practice), hepatitis B (known positive HBV
             surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus
             (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined
             as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are
             eligible. Patients positive for hepatitis C (hepatitis C virus [HCV]) antibody are
             eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of durvalumab. The following are exceptions to this criterion:

               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
                  articular injection)

               -  Systemic corticosteroids at physiologic doses not to exceed << 10 mg/day >> of
                  prednisone or its equivalent

               -  Steroids as premedication for hypersensitivity reactions (e.g., computed
                  tomography [CT] scan premedication)

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
             Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to
             30 days after the last dose of IP

          -  Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control from
             screening to 90 days after the last dose of durvalumab monotherapy

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug
             excipients

          -  Patients may not have received prior anti-PD-1, anti PD-L1 including durvalumab or
             anti CTLA-4 drugs

          -  Judgment by the investigator that the patient is unsuitable to participate in the
             study and the patient is unlikely to comply with study procedures, restrictions and
             requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:6-months progression-free survival (PFS) rate
Time Frame:6 months
Safety Issue:
Description:Will be calculated as proportion along with 95% confidence intervals (CI) using the Clopper-Pearson method. Chi-square test or Fisher's exact test will be used to compare the 6-months PFS rate between the different groups stratified by different factors, respectively. Logistics regression model will be further employed to test the adjusted effect of each factor on 6-month PFS rate after adjusting for other clinical factors and demographic factors.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 5 years
Safety Issue:
Description:Will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test, respectively. The OS of each patient group at specific time points, such as 6 months, 1 year, 3 year, and 5 year, etc. will be also estimated alone with 95% CI. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' OS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
Measure:PFS
Time Frame:Up to 5 years
Safety Issue:
Description:Will be estimated with the Kaplan-Meier method and compared between different groups using the log-rank test, respectively. The PFS of each patient group at specific time points, such as 6 months, 1 year, 3 year, and 5 year, etc. will be also estimated alone with 95% CI. Cox proportional hazards models will be further used in the multivariable analyses to assess adjusted effect of dose levels on the patients' PFS after adjusting for other factors. Interaction terms between these factors will also be tested for statistical significance. The proportional hazards assumption will be evaluated graphically and analytically with regression diagnostics. Violations of the proportional hazards assumptions will be addressed by use of time-dependent covariates or extended Cox regression models.
Measure:Incidence of adverse events (AEs)
Time Frame:Up to 90 days post treatment
Safety Issue:
Description:Safety profile of the regimen will be listed and summarized overall and by prognostic factor. Adverse events will also be listed by severity, seriousness, and by system organ class. The number and percentage of subjects who experience AEs will be presented in tabular and/or graphical format and summarized descriptively, where appropriate. No formal statistical comparison between the different factors will be performed. AEs will be presented with and without regard to causality based on the investigator's judgment. The frequency of overall toxicity, categorized by toxicity grades 1 through 5, will be described. Additional summaries will be provided for AEs that are observed with higher frequency.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Emory University

Last Updated

February 7, 2020