Recruiting
Phase 1
Phase 2

Pembrolizumab with Chemo

Sponsor:

Vanderbilt-Ingram Cancer Center

Code:

NCT05501665

Conditions

Lung Non-Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Stage III Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Carboplatin

Computed Tomography

Fludeoxyglucose F-18

Nab-paclitaxel

Study Details

Brief summary:

This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab, cemiplimab, atezolizumab or nivolumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs like carboplatin, pemetrexed, and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.

Conditions

Lung Non-Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Stage III Lung Cancer

Study ID

NCT05501665

Start date

May 9, 2023

Status verified date

Oct, 2024

Completion date

Feb 1, 2027

Anticipated

Primary completion date

Feb 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age >= 18 years at time of informed consent
  • • Histologically documented or cytologically confirmed diagnosis of stage IVA or IVB (M1b or M1c) or locally advanced (not eligible for standard of care \[SOC\] chemoradiation) non-small cell lung cancer with evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria
  • Available tumor material (< 6 months old) adequate for confirmation of programmed cell death 1 ligand 1 (PD-L1) expression per local standard of care testing
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Adequate organ function to receive therapy as determined by investigators and other treating physicians
  • Participants with brain metastases that can be comprehensively managed with surgery and/or stereotactic radiosurgery, prior to initiation of chemo-immunotherapy are allowed. Number of brain metastases allowed is not specified at eligibility is at discretion of investigator
  • Contraceptive use should be initiated or continued per guidance in labeling for approved chemotherapies
  • Female patients must be non-pregnant and not breastfeeding.

  • If woman of childbearing potential (WOCBP), must utilize highly effective contraceptive method (failure rate of < 1% per year) throughout intervention period and continued per guidance specified in labeling for approved chemotherapies. Must have negative pregnancy test (serum or urine) within 1 week prior to initiation of first cycle of therapy
  • Eligible for immunotherapy-based systemic regimens per judgment of patient's study physician
  • Able to submit written informed consent

Exclusion Criteria:

  • Mixed small cell histology
  • Confirmed candidate (per study physician) for alternative systemic therapy if preferred by treating physician (i.e. mEGFR, ALK, KRAS G12C or ROS1 mutations). Testing not required for enrollment
  • Brain metastases that would require administration of whole brain radiotherapy for management on required screening brain MRI within 21 days of day 1 of study treatment
  • Symptomatic malignant ascites or malignant pleural effusion (sampling not required). Pleural metastases are allowed if deemed targetable with radiotherapy
  • Major surgery (requiring general anesthesia or at discretion of study physician) within 4 weeks prior to study enrollment that would prevent treatment with SiCARIO regimen
  • History of organ transplant requiring therapeutic immunosuppression
  • Known clinically significant (per study physician) acute or chronic infections including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or active tuberculosis (testing not required). Patients with HBV and HCV must be on stable dose of antiviral therapy on study entry
  • Uncontrolled intercurrent illness including, but not limited to, New York Heart Association (NYHA) class III-IV congestive heart failure, uncontrolled hypertension (average systolic blood pressure greater than or equal to 140 or average diastolic blood pressure greater than or equal to 90 despite optimal medical therapy), unstable angina pectoris, cardiac arrythmia, active peptic ulcer disease, bleeding diatheses or psychiatric illness that would limit in the judgment of the study physician
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of day 1 of study treatment
  • History of prior independent malignancy within 3 years of enrollment, except for adequately treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma in situ (e.g. cervix or non-invasive bladder cancer)
  • Receipt of prior >1 cycle of immune checkpoint inhibitor for current malignancy (prior cytotoxic chemotherapy is allowed)
  • Prior radiotherapy that would preclude delivery of protocol- based radiotherapy to normal organ tolerance per patient's study physician
  • Current or prior use of immunosuppressive medications within 28 days of enrollment with exception of intranasal or inhaled corticosteroids or systemic steroids at physiologic doses (equivalent to less than or equal to 10 mg/day of prednisone). Systemic steroids required during therapy for adverse event (AE) management and for residual neurologic complications from management of central nervous system (CNS) metastases are allowed at doses exceeding 10 mg/day of prednisone equivalents
  • Active autoimmune disease requiring systemic treatment within past 1 year
  • Receipt of live attenuated vaccine within 30 days of enrollment
  • Use of prohibited concomitant drug within 30 days of enrollment
  • Known severe (>= grade 3 Common Terminology Criteria for Adverse Events \[CTCAE\]) hypersensitivity to study intervention or formulation
  • Concurrent enrollment in another clinical trial (unless observational or within follow-up period)
  • Any condition at discretion of investigator that will preclude participation in the study

Study Design

Enrollment

25 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation)

Patients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm II (carboplatin, pemetrexed, cemiplimab, radiation)

Patients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation)

Patients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation)

Patients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation)

Patients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation)

Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation)

Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm VIII (pembrolizumab, radiation)

Patients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm IX (atezolizumab, radiation)

Patients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm X (cemiplimab-rwlc, radiation)

Patients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions.

All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

experimental: Arm XI (nivolumab, ipilumumab, radiation)

Patients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Interventions

Biospecimen Collection

Correlative studies

Carboplatin

Given carboplatin

Computed Tomography

Undergo PET/CT

Fludeoxyglucose F-18

Given IV

Nab-paclitaxel

Given nab-paclitaxel

Pembrolizumab

Given pembrolizumab

Pemetrexed

Given pemetrexed

Positron Emission Tomography

Undergo PET/CT

Radiation Therapy

Undergo radiation therapy

[18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan

Undergo PET scan

Ipilimumab

Given Ipilimumab

Nivolumab

Given Nivolumab

Cemiplimab

Given Cemiplimab

Atezolizumab

Given Atezolizumab

Primary outcome measure

  • Incidence of adverse events [ Time Frame: Up to 2 years ]
  • Best overall response rate [ Time Frame: Within 6 months ]

Central Contacts and Locations

Central contacts

Vanderbilt-Ingram Service for Timely Access

800-811-8480cip@vumc.org

Locations

Vanderbilt University/Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Vanderbilt-Ingram Service for Timely Access

800-811-8480cip@vumc.org

Principal Investigator:

Evan Osmundson, MD, PhD

More Information

Sponsor

Vanderbilt-Ingram Cancer Center

Last update posted

Oct 17, 2024

Last verified

Oct, 2024

Keywords

  • Oligometastasis
  • Adaptive Radiotherapy
  • Immunotherapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt-Ingram Cancer Center on 2024-10-17.