Clinical Trials /

Durvalumab in Combination With Chemotherapy in Virus-infected Patients With Non-small Cell Lung Cancer

NCT04499053

Description:

This is a phase II trial of durvalumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection (cohort 1) or hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (cohort 2) will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. We hypothesized that Durvalumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV, HBV, or HCV infection.

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

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Durvalumab in Combination With Chemotherapy in Virus-infected Patients With Non-small Cell Lung Cancer
  • Official Title: A Phase II Trial of Durvalumab (MEDI4736) in Combination With Chemotherapy in Virus-infected Patients With Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: STUDY00002036
  • NCT ID: NCT04499053

Conditions

  • Carcinoma, Non-Small Cell Lung

Interventions

DrugSynonymsArms
Durvalumabdurvalumab (MEDI4736)

Purpose

This is a phase II trial of durvalumab in combination of platinum-based chemotherapy. Patients with stage IV Non-Small-Cell-Lung Cancer (NSCLC) with human immunodeficiency virus (HIV) infection (cohort 1) or hepatitis B virus (HBV), or hepatitis C virus (HCV) infection (cohort 2) will be eligible. Patients will receive standard platinum-based chemotherapy plus durvalumab for 4 cycles (every 3 weeks), followed by durvalumab (with or without pemetrexed for non-squamous NSCLC) maintenance therapy. We hypothesized that Durvalumab in combination with standard chemotherapy is safe and effective for the treatment of stage IV NSCLC in patients with HIV, HBV, or HCV infection.

Detailed Description

      This is an open-label, non-randomized phase II trial of durvalumab in combination with
      platinum-based doublet chemotherapy. Patients with stage IV NSCLC with HIV (cohort 1) or
      HBV/HCV (cohort 2) infection will be eligible. Patients will receive standard chemotherapy
      plus durvalumab (1500 mg Q3W) every three weeks for 4 cycles, followed by maintenance
      treatment with durvalumab (1500 mg Q4W; with or without pemetrexed for non-squamous NSCLC per
      the discretion of the investigator).

      Patient will be enrolled into the trial using an optimal two-stage phase II trial design. If
      0 of the 7 achieved a response, no further patients will be enrolled in that cohort. If 1 or
      more of the first 7 patients has a response, accrual would continue until a total of 18
      patients have been enrolled in that cohort. Objective response will be evaluated using the
      Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Safety and tolerability will be
      evaluated by assessing the incidence of treatment-related grade 3 or higher AEs.
      Treatment-related grade 3 or higher AEs will be defined as any grade 3 or higher AEs that
      occur during the first 42 days of treatment and are related to the study treatment. AEs will
      be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

      Subjects will receive 4 cycles of combination treatment: durvalumab (1500 mg every 3 weeks)
      in combination with platinum-based doublet chemotherapy. The platinum-based doublet
      chemotherapies (carboplatin plus paclitaxel/nab-paclitaxel vs. pemetrexed plus
      carboplatin/cisplatin) are dependent on the tumor histology of the subject (squamous vs.
      non-squamous). Only subjects who achieve stable disease or better radiological response after
      4 cycles of induction treatment will be eligible to continue study treatment in maintenance.
      The choice to treat non-squamous subjects with pemetrexed maintenance after the 4 induction
      cycles will be determined by the investigator.
    

Trial Arms

NameTypeDescriptionInterventions
durvalumab (MEDI4736)ExperimentalDurvalumab 1500 mg, intravenous, every 3 weeks for 4 cycles, followed by 1500 mg, intravenous, every 4 weeks (maintenance treatment)
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with stage IV NSCLC who had undergone no previous systemic therapy for stage
             IV disease.

          2. Cohort 1: Patients with HIV must be on an effective combination anti-retroviral
             therapy (cART) regimen for ≥ 4 weeks Cohort 2: Patients with chronic HBV infection
             will be eligible. Patients with positive hepatitis B core antibody (anti-HBc) but
             negative surface antigen (HBsAg) will be eligible. Those with detectable HBV DNA who
             are negative for HBsAg will also be eligible. For hepatitis C, patients with
             detectable HCV RNA will be eligible. Those who have completed antiviral therapy for
             HCV and undetectable HCV RNA will also be eligible.

          3. Age > 18 years at time of study entry.

          4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          5. Body weight >30kg

          6. Adequate normal organ and marrow function as defined below:

               -  Hemoglobin ≥ 9.0 g/dL

               -  Absolute neutrophil count (ANC) ≥ 1,000 per mm3

               -  Platelet count ≥ 100,000 per mm3

               -  CD4 T-cell count ≥ 100 per mm3 for HIV-infected patients

               -  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 only in consultation with their
                  physician.

               -  AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
                  metastases are present, in which case it must be ≤5x ULN

               -  Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40
                  mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
                  urine collection for determination of creatinine clearance:

             Males: Creatinine CL (mL/min) = [Weight (kg) x (140 - Age)] / [72 x serum creatinine
             (mg/dL)] Females: Creatinine CL (mL/min) = [Weight (kg) x (140 - Age) x 0.85] / [72 x
             serum creatinine (mg/dL)]

          7. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrheic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

          8. 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.

          9. Must have a life expectancy of at least 12 weeks.

        Exclusion Criteria:

          1. Sensitizing EGFR mutations (deletion in exon 19, L858R in exon 21, G719X, and L861Q)
             and/or ALK translocations by locally approved laboratory testing including blood-based
             liquid biopsy.

          2. Coinfection of HIV + HBV or HIV + HCV (coinfection of HIV and HCV allowed if HCV is
             cured). Coinfection of HBV and HCV is allowed if otherwise eligible.

          3. No measurable disease.

          4. Receipt of the last dose of anticancer therapy (chemotherapy, targeted therapy) ≤ 21
             days prior to the first dose of study treatment.

          5. Any unresolved toxicity NCI CTCAE Grade ≥ 2 from previous anticancer therapy
             (chemotherapy, targeted therapy, radiation therapy) with the exception of alopecia,
             vitiligo, and the laboratory values defined in the inclusion criteria.

          6. Patients who have had whole brain radiation therapy (WBRT) during the previous 2 weeks
             before treatment (no washout period is required for patients who have received
             stereotactic body radiation therapy).

          7. Subject has had major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic)
             within 4 weeks prior to starting study drug or has not recovered from side effects of
             such procedure (≥ grade 2 AE related to such procedure). Video-assisted thoracic
             surgery (VATS) and mediastinoscopy will not be counted as major surgery and subject
             can be enrolled in the study ≥ 1 week after the procedure.

          8. History of allogenic organ transplantation.

          9. Active or prior documented autoimmune or inflammatory disorders (including
             inflammatory bowel disease [e.g., colitis or Crohn's disease], 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:

             i. Patients with vitiligo or alopecia ii. Patients with hypothyroidism (e.g.,
             following Hashimoto syndrome) stable on hormone replacement iii. Any chronic skin
             condition that does not require systemic therapy iv. Patients without active disease
             in the last 5 years may be included

         10. 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, or psychiatric
             illness/social situations that would limit compliance with study requirement,
             substantially increase risk of incurring AEs or compromise the ability of the patient
             to give written informed consent.

         11. History of a previous malignancy within the last 2 years, with the exception of early
             stage cancers that are at very low risk of recurrence, such as non-melanoma skin
             cancer, papillary carcinoma of the thyroid, or carcinoma in situ of the prostate,
             cervix, or breast.

         12. Previously untreated central nervous system (CNS) metastases or leptomeningeal
             disease. Patients who have had whole brain radiation therapy (WBRT) during the
             previous 2 weeks before treatment (no washout period is required for patients who have
             received stereotactic body radiation therapy).

         13. Active tuberculosis (clinical evaluation that includes clinical history, physical
             examination and radiographic findings, and TB testing in line with local practice).

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

             i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
             articular injection) ii. Systemic corticosteroids at physiologic doses not to exceed
             10 mg/day of prednisone or its equivalent iii. Steroids as premedication for
             hypersensitivity reactions (e.g., CT scan premedication)

         15. Receipt of live attenuated vaccine within 30 days prior to the first dose of
             investigational product (IP). Note: Patients, if enrolled, should not receive live
             vaccine whilst receiving study treatment and up to 30 days after the last dose of IP.

         16. Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential who are not willing to employ effective birth control.

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

         18. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4.

         19. 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:Adverse Events
Time Frame:4 cycles (12 weeks)
Safety Issue:
Description:Incidence of treatment-emergent Adverse Events according to NCI CTCAE v5.0.

Secondary Outcome Measures

Measure:Changes in Viral Load
Time Frame:4 cycles (12 weeks)
Safety Issue:
Description:Evaluate changes in viral load with study treatment
Measure:Change in Cytokine Secretion Assays
Time Frame:36 months
Safety Issue:
Description:Cytokine secretion assays will be performed on blood samples before, during, and after treatment.
Measure:Correlation of Immune biomarkers to response
Time Frame:36 months
Safety Issue:
Description:Baseline immune biomarkers will be compared between responders and non-responders to find predictive biomarkers associated with response to treatment.
Measure:Correlation of bTMB and treatment outcome
Time Frame:36 months
Safety Issue:
Description:The blood tumor mutational burden (bTMB) between responders and non-responders will be compared.

Details

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

Trial Keywords

  • Lung Cancer
  • Non-Small Cell Lung Cancer
  • Durvalumab

Last Updated

July 30, 2020