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

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ClinicalTrials.gov Identifier: NCT03999710
Recruitment Status : Recruiting
First Posted : June 27, 2019
Last Update Posted : July 22, 2019
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Lung Cancer Nsclc NSCLC Stage II NSCLC, Stage III Radiation: Radiation Therapy Drug: Durvalumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Durvalumab With Thoracic Radiation Therapy Without Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer (DART)
Actual Study Start Date : July 19, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Non-Small Cell Lung Cancer
All participants have locally-advanced non-small cell lung cancer, Stage II-III.
Radiation: Radiation Therapy
Treatment will consist of 60 Gy in 30 fractions to fields encompassing gross tumor and lymph nodes.

Drug: Durvalumab
A dose of 1500mg (for patients >30kg in weight) will be administered using an IV bag containing 0.9% (w/v) saline or 5% (w/v) dextrose, with a final durvalumab concentration ranging from 1 to 15 mg/mL, and delivered through an IV administration set with a 0.2- or 0.22- μm filter.




Primary Outcome Measures :
  1. 2-year PFS rate [ Time Frame: 2 years ]
    Demonstrate an improvement in 2-year PFS rate compared to historical results.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03999710


Contacts
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Contact: Andreas Rimner, MD 212-639-6025 rimnera@mskcc.org
Contact: Jamie Chaft, MD 646-888-4545 chaftj@mskcc.org

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Andreas Rimner, MD    212-639-6025      
Memoral Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Andreas Rimner, MD    212-639-6025      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Samuel Funt, MD    646-422-4558      
United States, New York
Memorial Sloan Kettering Cancer Center @ Commack Recruiting
Commack, New York, United States, 11725
Contact: Andreas Rimner, MD    212-639-6025      
Memoral Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Andreas Rimner, MD    212-639-6025      
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Andreas Rimner, MD    212-639-6025      
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Andreas Rimner, MD    212-639-6025      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Andreas Rimner, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03999710     History of Changes
Other Study ID Numbers: 19-218
First Posted: June 27, 2019    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Lung Cancer
Non Small Cell Lung Cancer
Radiation therapy
durvalumab
19-218
Memorial Sloan Kettering Cancer Center

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Bronchial Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs