Clinical Trials /

Treating Early-stage Non-Small Cell Lung Cancer With Durvalumab and Radiation Therapy

NCT04716946

Description:

The purpose of this study is to find out whether treatment with the study drug durvalumab combined with a type of radiation therapy called stereotactic body radiation (SBRT) is a more effective treatment for early-stage non-small cell lung cancer (NSCLC) than SBRT alone.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treating Early-stage Non-Small Cell Lung Cancer With Durvalumab and Radiation Therapy
  • Official Title: Stereotactic Body Radiation Therapy With Consolidation Durvalumab in High-Risk Early-Stage Non-Small Cell Lung Cancer - A Phase II Single-Arm Trial

Clinical Trial IDs

  • ORG STUDY ID: 20-415
  • NCT ID: NCT04716946

Conditions

  • NSCLC
  • Non-small Cell Lung Cancer
  • Lung Cancer
  • Non-small Cell Lung Cancer Stage I
  • Non-small Cell Lung Cancer Stage II
  • Non-small Cell Lung Cancer Stage III
  • Non-small Cell Lung Cancer Stage IIIA
  • PD-L1 Gene Mutation

Interventions

DrugSynonymsArms
DurvalumabParticipants with Early-stage Non-Small Cell Lung Cancer

Purpose

The purpose of this study is to find out whether treatment with the study drug durvalumab combined with a type of radiation therapy called stereotactic body radiation (SBRT) is a more effective treatment for early-stage non-small cell lung cancer (NSCLC) than SBRT alone.

Trial Arms

NameTypeDescriptionInterventions
Participants with Early-stage Non-Small Cell Lung CancerExperimentalParticipants will be diagnosed with Stage I-IIIA NSCLC and will be ineligible for surgery and will have any level of PD-L1
  • Durvalumab

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. Written informed consent and any locally required authorization obtained
             from the patient/legal representative prior to performing any protocol- related
             procedures.

          -  Patient age ≥ 18 at time of consent

          -  Early stage NSCLC (Stage I to IIIA; T1-4 excluding patients with satellite nodules in
             the same or ipsilateral lobes, N0; AJCC 8th edition)

          -  Ineligible for or unwilling to undergo surgical resection. Reasons for surgical
             ineligibility include: medically inoperable or surgically unresectable (due to tumor
             size, location etc.), as assessed by MSKCC thoracic surgeon or multi-disciplinary
             tumor board consensus. Reasons for ineligibility or patient's unwillingness to undergo
             surgical resection must be clearly documented.

          -  Histological and/or cytological confirmation of NSCLC as per standard of care biopsy;
             no additional research protocol-specific biopsy is needed.

          -  ECOG/WHO PS 0-1 (KPS 70-100)

          -  Candidates for definitive SBRT

             ° If, after candidates have been planned for RT, they are unable to be treated with
             the institutional dose constraints as listed in the appendix, they will be labeled
             ineligible and removed from the study. Ineligible patients will be replaced.

          -  A PFS of <60% (at least 40% risk for disease progression) at 2 years based on an
             MSKCC-developed risk prediction model (see section 9.0).

          -  Body weight > 30kg

          -  Adequate normal organ and marrow function as defined below:

               -  Hemoglobin ≥9.0 g/dL

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

               -  Platelet count ≥75 x 10^9/L (>75,000 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 only in consultation with their
                  physician.

               -  AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered postmenopausal 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 postmenopausal 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).

          -  Must have a life expectancy of at least 12 weeks

        Exclusion Criteria:

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

          -  Previous thoracic radiation precluding definitive SBRT to the current tumor.

          -  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:

               1. Patients with vitiligo or alopecia

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

               3. Any chronic skin condition that does not require systemic therapy

               4. Patients without active disease in the last 5 years may be included but only
                  after consultation with the PI

               5. Patients with celiac disease controlled by diet alone

          -  Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the
             exception of alopecia, vitiligo, and the laboratory values defined in the inclusion
             criteria

               1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after
                  consultation with the PI.

               2. Patients with irreversible toxicity not reasonably expected to be exacerbated by
                  treatment with durvalumab may be included only after consultation with the PI.

          -  Prior/Current Therapies:

               1. Treatment with a monoclonal antibody within 4 weeks prior to study Day 1 or has
                  not recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents
                  administered > 4 weeks earlier (intraocular bevacizumab is acceptable).

               2. Prior chemotherapy or targeted small molecule therapy, within 3 weeks prior to
                  study Day 1 or has not recovered (i.e., ≥ Grade 1 at baseline) from adverse
                  events due to a previously administered agent).

               3. Prior therapy with an anti-PD-1, anti-PD-L1, including durvalumab, anti-PDL2,
                  anti-CD137, anti-Cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4) antibody,
                  or any other antibody or drug specifically targeting T-cell co-stimulation or
                  checkpoint pathways.

               4. 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) e. Any concurrent
             chemotherapy, 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. f. Prior chemotherapy for this diagnosis of lung cancer

          -  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.

          -  Severe concurrent illness:

               1. Known psychiatric or substance abuse disorders that would interfere with
                  cooperation with the requirements of the trial.

               2. Known additional malignancy that is progressing or requires active treatment.
                  Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of
                  the skin, or in situ cervical cancer that has undergone potentially curative
                  therapy.

               3. 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 (HCV) antibody are eligible only if
                  polymerase chain reaction is negative for HCV RNA.

               4. Active infection requiring systemic therapy.

               5. Evidence of interstitial lung disease or active, non-infectious pneumonitis.

               6. Clinically significant (i.e., active) cardiovascular disease: symptomatic
                  cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial
                  infarction (< 6 months prior to enrollment), unstable angina, congestive heart
                  failure (≥ New York Heart Association Classification Class II), or serious
                  cardiac arrhythmia requiring medication.

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

             a. Highly effective methods of contraception, defined as one that results in a low
             failure rate (ie, less than 1% per year) when used consistently and correctly are
             described in Appendix B. Note that some contraception methods are not considered
             highly effective (e.g. male or female condom with or without spermicide; female cap,
             diaphragm, or sponge with or without spermicide; non-copper containing intrauterine
             device; progestogen-only oral hormonal contraceptive pills where inhibition of
             ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is
             considered highly effective]; and triphasic combined oral contraceptive pills).

          -  Live vaccination within 4 weeks prior to the first dose of durvalumab and while on
             trial is prohibited except for administration of inactivated vaccines.

          -  Connective tissue disorders or idiopathic pulmonary fibrosis involving the lungs
             and/or esophagus

          -  Known actionable EGFR or ALK mutation

          -  Known contraindications to radiotherapy

          -  History of leptomeningeal carcinomatosis

          -  History of active primary immunodeficiency

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

          -  Prior randomization or treatment in a previous durvalumab clinical study regardless of
             treatment arm assignment.

          -  Participants must not donate blood while on durvalumab therapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:The primary objective of the study is to evaluate 2- year progression-free survival (PFS) per RECIST 1.1 with durvalumab combined with stereotactic body radiation therapy (SBRT) compared to historical controls with SBRT alone.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Durvalumab
  • NSCLC
  • Non-small Cell Lung Cancer
  • Non-small Cell Lung Cancer Stage I
  • Non-small Cell Lung Cancer Stage II
  • Non-small Cell Lung Cancer Stage III
  • Non-small Cell Lung Cancer Stage IIIA
  • Lung Cancer
  • PD-L1 Gene Mutation
  • Early stage NSCLC
  • 20-145
  • Memorial Sloan Kettering Cancer Center

Last Updated

June 8, 2021