BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab

January 26, 2023 updated by: Brown University

BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab for Patients With Resectable Stage IB - III Non-Small Cell Lung Cancer

This single-arm phase 2 study will enroll patients with resectable and operable stage IB - III non-small cell lung cancer and treat them with pre-operative ipilimumab + nivolumab plus low-dose stereotactic body radiation therapy (SBRT) delivered concurrently. Only patients who proceed to surgery will be evaluable for the primary endpoint. The primary efficacy outcome measurement will be pathologic response (including Major Pathologic Response (MPR), and Complete Pathologic Response (CPR)). Secondary outcome measures include safety, and exploratory biomarkers of immune response in pre- and post-operative blood and tissue. A two-stage design will stop the study if fewer than 3 of the first 9 evaluable patients do not achieve MPR. An early stopping rule for safety will stop the study if more than 12 patients are enrolled to find the first 9 evaluable patients.

Study Overview

Status

Recruiting

Study Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Contact:
        • Principal Investigator:
          • Thomas A DiPetrillo, MD
        • Principal Investigator:
          • Christopher G Azzoli, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Pathologically confirmed NSCLC
  2. Age > 18
  3. ECOG Performance Status 0-1.
  4. Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1 second (FEV1) must be > 0.8 L or be > 35% of the predicted value. Postoperative predicted DLCO ≥ 35% is required.
  5. Resectable stage IB-IIIB (T2-3N0, T1-T3N1-2) NSCLC (per the 8th Edition American Joint Committee on Cancer (AJCC) classification) who are candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if the surgeon and study team deem it to be resectable.
  6. N2 nodes must be discrete (ie, not invading surrounding structures). If patients have N2 disease, as suspected by CT or PET, histologic proof of N2 status is recommended.
  7. Patients must be evaluated by a Thoracic Surgeon prior to registration. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Absence of major associated comorbidities that increase the surgery risk to an unacceptable level.
  8. No prior history of thoracic radiation.
  9. Adequate Organ and marrow function as defined below

    • leukocytes ≥2,000/mcL,
    • absolute neutrophil count ≥1,000/mcL,
    • platelets ≥100,000/mcL,
    • Hemoglobin >8.0 g/dL
    • Total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
    • creatinine within normal institutional limits OR creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  10. Patients are capable of giving informed consent and/or have an acceptable surrogate capable of giving consent on the subject's behalf.
  11. Nonpregnant and non-nursing. The effect of ipilimumab and nivolumab on the fetus is unknown.
  12. Women of childbearing potential (WOCBP) must 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 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year.
  13. Evidence of postmenopausal status or negative urinary or serum pregnancy test for female premenopausal 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:
  14. Women <50 years of age would be considered postmenopausal 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).
  15. Women ≥50 years of age would be considered postmenopausal 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).
  16. 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.
  17. Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.

Exclusion Criteria:

  1. Pathologically confirmed NSCLC *
  2. Age > 18 *
  3. ECOG Performance Status 0-1.
  4. Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1 second (FEV1) must be > 0.8 L or be > 35% of the predicted value. Postoperative predicted DLCO ≥ 35% is required.
  5. Resectable stage IB-IIIB (T2-3N0, T1-T3N1-2) NSCLC (per the 8th Edition American Joint Committee on Cancer (AJCC) classification) who are candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if the surgeon and study team deem it to be resectable.
  6. N2 nodes must be discrete (ie, not invading surrounding structures). If patients have N2 disease, as suspected by CT or PET, histologic proof of N2 status is recommended.
  7. Patients must be evaluated by a Thoracic Surgeon prior to registration. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Absence of major associated comorbidities that increase the surgery risk to an unacceptable level. *
  8. No prior history of thoracic radiation.
  9. Adequate Organ and marrow function as defined below

    • leukocytes ≥2,000/mcL,
    • absolute neutrophil count ≥1,000/mcL,
    • platelets ≥100,000/mcL,
    • Hemoglobin >8.0 g/dL
    • Total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
    • creatinine within normal institutional limits OR creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  10. Patients are capable of giving informed consent and/or have an acceptable surrogate capable of giving consent on the subject's behalf.
  11. Nonpregnant and non-nursing. The effect of ipilimumab and nivolumab on the fetus is unknown.
  12. Women of childbearing potential (WOCBP) must 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 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year.
  13. Evidence of postmenopausal status or negative urinary or serum pregnancy test for female premenopausal 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:
  14. Women <50 years of age would be considered postmenopausal 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).
  15. Women ≥50 years of age would be considered postmenopausal 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).
  16. 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.
  17. Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Protocol Therapy
Ipilimumab: 1mg/kg IV day 1. Nivolumab: 3mg/kg IV days 1, 15, 29. SBRT delivered as 1-2 fractions to the gross primary tumor and nodal disease following day 1 infusion and completed by day 3 (7Gy x 1; 4Gy x 2).
1mg/kg IV on day 1 (1 dose total)
3mg/kg (to a maximum of 240mg) IV on days 1, 15, 29 (+/- 3 days) (3 doses total)
1 fraction or 2 fractions delivered to the gross primary tumor and nodal disease, following the first treatment with ipilimumab + nivolumab on days 1-3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients with a Pathologic Response
Time Frame: From beginning of study treatment to approximately day 49-63 on study.
Assess Pathologic Response (major pathologic response and complete pathologic response) following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab.
From beginning of study treatment to approximately day 49-63 on study.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: Beginning of study treatment through 90 days post study treatment completion.
Assess safety and operative morbidity following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab and surgery.
Beginning of study treatment through 90 days post study treatment completion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Christopher G Azzoli, MD, Brown University
  • Principal Investigator: Thomas A DiPetrillo, MD, Brown University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 5, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

January 1, 2025

Study Registration Dates

First Submitted

October 15, 2020

First Submitted That Met QC Criteria

June 14, 2021

First Posted (Actual)

June 22, 2021

Study Record Updates

Last Update Posted (Actual)

January 27, 2023

Last Update Submitted That Met QC Criteria

January 26, 2023

Last Verified

January 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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