Clinical Trials /

Determining Whether Durvalumab in Combination With Radiation Therapy Can Prevent the Progression of Non-Small Cell Lung Cancer

NCT03999710

Description:

The purpose of this study is to see if Durvalumab and radiation therapy can delay the worsening of disease in patients with non-small cell lung cancer normally treated with sequential chemotherapy followed by radiation therapy.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Determining Whether Durvalumab in Combination With Radiation Therapy Can Prevent the Progression of Non-Small Cell Lung Cancer
  • Official Title: Durvalumab With Thoracic Radiation Therapy Without Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (DART)

Clinical Trial IDs

  • ORG STUDY ID: 19-218
  • NCT ID: NCT03999710

Conditions

  • Non Small Cell Lung Cancer
  • Lung Cancer
  • Nsclc
  • NSCLC Stage II
  • NSCLC, Stage III

Interventions

DrugSynonymsArms
DurvalumabNon-Small Cell Lung Cancer

Purpose

The purpose of this study is to see if Durvalumab and radiation therapy can delay the worsening of disease in patients with non-small cell lung cancer normally treated with sequential chemotherapy followed by radiation therapy.

Trial Arms

NameTypeDescriptionInterventions
Non-Small Cell Lung CancerExperimentalAll participants have locally-advanced non-small cell lung cancer, Stage II-III.
  • 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, including screening evaluations.

          -  Patient age >/= 18 at time of consent

          -  Locally-advanced NSCLC (stage II-III)

          -  Ineligible for resection and concurrent CRT as determined by one of the following
             reasons: Medically inoperable, surgically unresectable (including N3 nodal disease),
             medically unfit or unsafe for chemotherapy, or other reason deemed appropriate by the
             investigator and approved by PI.

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

          -  ECOG/WHO PS 0-2

          -  Candidates for definitive RT to 60 Gy in 30 fractions

          -  Tumor able to be treated with radiation conforming to the following dose constraints:

               -  Mean lung dose <21 Gy, V20 <37-40%, NTCP <25%

               -  Hear V30 </= 50%

          -  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 mm3)

               -  Platelet count >/= 75 x 10^9/L (>/= 75,000 per mm3)

               -  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

               -  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)] / [72 x serum creatinine(mg/dL)] x
        0.85

          -  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 would be considered post-menopausal
                  if they have been amenorrheic for 12 months 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, or
                  underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy
                  or hysterectomy)

          -  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.

          -  Must have a life expectancy of at least 12 weeks

        Exclusion Criteria:

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

          -  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

          -  Previous thoracic radiation precluding definitive RT

          -  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 study physician

               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 >/= neuropathy will be evaluated on a case-by-case basis
                  after consultation with the Study Physician

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

          -  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 agents (excluding Grade 2 peripheral
                  neuropathy)

               3. Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137,
                  anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLAA-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

          -  Sever concurrent illness:

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

               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), 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 Table 1. 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).

             i. Barrier/Intrauterine Methods: Copper T intrauterine device;
             Levonorgestrel-releasing intrauterine system (e.g., Mirena) ii. Hormonal Methods:
             Implants - Etonogestrel-releasing implants (e.g. Implanon or Norplant); Intravaginal -
             Ethinylestradiol/etonogestrel-releasing intravaginal devices (e.g., NuvaRing);
             Injection - Medroxyprogesterone (e.g., Depo-Provera); Combined Pill - normal and low
             dose combined oral contraceptive pill; Patch -
             Norelgestromin/ethinylestradiol-releasing transdermal system (e.g., Ortho Evra);
             Minipills: Progesterone based oral contraceptive pill using desogestrel (Cerazette is
             currently the only highly effective progesterone-based)

          -  Live vaccination with 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

          -  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

          -  Criteria specific for concurrent ChemoRT. The PI, Co-PI or a delegate will approve
             eligibility taking into account the below:

               1. Hearing impairment

               2. Neuropathy

               3. Other medical concern for the safety of cytotoxic chemotherapy

               4. Other clinical consideration not specified but patient felt to be inappropriate
                  for chemoradiation based on multidisciplinary evaluation

               5. Fitness consideration not otherwise specified but candidacy felt appropriate
                  after multidisciplinary evaluation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:2-year PFS rate
Time Frame:2 years
Safety Issue:
Description:Demonstrate an improvement in 2-year PFS rate compared to historical results.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Lung Cancer
  • Non Small Cell Lung Cancer
  • Radiation therapy
  • durvalumab
  • 19-218
  • Memorial Sloan Kettering Cancer Center

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