Concurrent or Sequential Immunotherapy and Radiation Therapy in Patients With Metastatic Lung Cancer (COSINR)

  • STATUS
    Recruiting
  • End date
    Dec 21, 2024
  • participants needed
    80
  • sponsor
    University of Chicago
Updated on 21 March 2022

Summary

Trial Design

  • Patients with stage IV non-small cell lung cancer are randomized to nivolumab/ipilimumab plus either sequential or concurrent stereotactic body radiotherapy (SBRT).
  • The primary endpoint is the phase I safety endpoint of SBRT dose for each body site.
  • The same starting SBRT dose levels are used in each arm. If two or more patients experience a dose-limiting toxicity (DLT) at the starting dose level, then the reduced dose level will be used (Section 7.1-Page 72).
  • DLT is defined as any grade ≥3 toxicity possibly, likely, or definitely related to SBRT plus nivolumab/ipilimumab (the combination and not the individual components).
  • Irradiated metastases will be grouped into one of five locations, which have different SBRT doses, and the DLTs will be attributed to the relevant organ system.
  • The starting and decreased SBRT dose levels are found in Table 2 (Page 20).
  • SBRT will be delivered in 3-5 fractions over the course of 1-1.5 weeks.
  • Patients in the sequential arm will begin immunotherapy between 1-7 days after completion of SBRT
  • Given the accrual data for IRB15-1130, the investigators anticipate that approximately 1/3 of patients will contribute metastasis to 2 locations. Since there are 2 arms, and 5 metastasis locations with 6 patients per location for the starting dose level, this translates to 40 patients for the starting dose level, and another 40 patients should each of the 5 locations require de-escalation to the lower dose level.
  • Secondary endpoints include comparisons of efficacy and toxicity between the arms, as well as interrogation of changes in the immune microenvironment induced by the two approaches.

Details
Condition Stage IV Small Cell Lung Cancer
Treatment Ipilimumab, Nivolumab, stereotactic body radiation therapy
Clinical Study IdentifierNCT03223155
SponsorUniversity of Chicago
Last Modified on21 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

\. Have a histologic diagnosis of stage IV NSCLC
\. Be willing and able to provide written informed consent/assent for the trial
\. Be greater than or equal to 18 years of age on day of signing informed consent
\. Have measurable disease based on RECIST 1.1 including at least two metastatic lesions that meet criteria for SBRT radiation
0.25 cc to 65 cc of viable tumor (i.e. primary disease or metastases) approximately 5cm in maximal dimension. Tumors larger than 65 cc can be partially treated
\. For biopsy identified patients: Be willing to undergo repeat biopsy of a target
\. Have a performance status of 0 or 1 on the ECOG Performance Scale
lesion before treatment and after radiation. Subjects for whom newly-obtained
\. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation
samples cannot be provided (e.g. inaccessible or subject safety concern) may
be exempted from this requirement after consultation with the Principal
Investigator
Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological
Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥ 100,000 / mcL Hemoglobin ≥ 9 g/dL
or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used
in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) OR ≥ 50 mL/min for
subject with creatinine levels > 1.5 X institutional ULN
Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total
bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects
with liver metastases Albumin ≥ 3.0 mg/dL aCreatinine clearance should be calculated per
institutional standard
Female subject of childbearing potential should have a negative urine or serum
pregnancy within 24hours prior to receiving the first dose of study medication. If the
urine test is positive or cannot be confirmed as negative, a serum pregnancy test will
be required
Female subjects of childbearing potential should be willing to use 2 methods of
birth control or be surgically sterile, or abstain from heterosexual activity for the
course of the study through 120 days after the last dose of study medication. Subjects
of childbearing potential are those who have not been surgically sterilized or have
not been free from menses for > 1 year
Male subjects should agree to use an adequate method of contraception starting
with the first dose of study therapy through 120 days after the last dose of study
therapy
Have an investigator determined life expectancy of at least 6 months
Patients whose tumors known to harbor an exon 19 deletion or exon 21 L858R EGFR
mutation must have progressed on or had intolerance to an EGFR TKI. Patients whose
tumors are known to harbor an ALK translocation must have progressed on or had
intolerance to an ALK inhibitor

Exclusion Criteria

Has received prior chemotherapy for NSCLC with the exception of neoadjuvant or
adjuvant platinum-based chemotherapy for NSCLC completed >6 months prior to
enrollment
Has prior exposure to anti-PD1/PD-L1 or anti-CTLA4 therapy
Is currently participating and receiving study therapy or has participated in a
study of an investigational agent and received study therapy or used an
investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a
dose of >10mg prednisone daily or equivalent at time of first dose of trial treatment
Has a known history of active TB (Bacillus Tuberculosis)
Hypersensitivity to nivolumab, ipilimumab, or any of its excipients
Has received radiation therapy within 2 weeks of study drug administration
Has a known additional malignancy that is progressing or requires active treatment
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer
Patients with untreated symptomatic brain metastases. Patients with treated brain
metastases will be allowed if brain imaging obtained greater than 7 days from
treatment reveals stable disease. Patients with small (< 3mm) asymptomatic brain
metastasis are allowed to enroll. Patients on steroids doses higher than 10 mg of
prednisone (or its equivalent) are excluded
Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment
Has known history of non-infectious pneumonitis that required steroids or active
pneumonitis
Has evidence of interstitial lung disease
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within
the projected duration of the trial, starting with the screening visit through 120
days after the last dose of trial treatment
If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected) then patient is not eligible for cohorts including SBRT to
liver lesions
Has received a live vaccine within 30 days of planned start of study therapy
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated
vaccines, and are not allowed
Has had prior radiation therapy (defined as >10% of prior prescription dose) to
the area planning to be treated with SBRT
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