Pembrolizumab After Lung SBRT for Medically Inoperable Early Stage Non-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT03574220|
Recruitment Status : Withdrawn (No accrual - closed by PRMC)
First Posted : June 29, 2018
Last Update Posted : April 7, 2020
The purpose of this study is to see whether patients who have early stage NSCLC bigger than a certain size might benefit from receiving additional medicinal drug to treat their cancer after the SBRT Surgeons and radiation doctors have understood for some time that the chances of cancer showing up in areas outside the chest are higher for patients with tumors bigger than 3 cm, (about 1 ¼ inches). However, it is not routine to offer chemotherapy or drug treatments after radiation or surgery for lung cancer for patients with early stage lung cancer. This is because giving extra treatment in the form of chemotherapy has not shown to help patients live longer. There has been reluctance to offer additional treatments, especially chemotherapy, to patients with lung cancer who could not have surgery because of their medical issues. Even if these patients were felt to be at a higher risk of their cancer coming back, there is hesitation because the treatments can be difficult to tolerate in frail patients.
Recently, there have been very important advances in the kinds of drug therapy that are used for lung cancer patients. These kinds of drugs are called immunotherapy since they work with the body's immune system to fight the cancer. These drugs have been shown to make patients with advanced, incurable lung cancer, live longer and also to be very safe with very limited side effects. Because of these favorable characteristics, cancer specialists are interested in using these drugs for patients with curable cancer and for patients who may be too fragile for traditional chemotherapy. In this way, patients who get SBRT are already known to be fragile so cancer doctors are interested in now studying this kind of drug in SBRT patients to see if it can make patients with large tumors do better. The idea of the study then is that the patient would receive their standard SBRT and if their tumor is of a certain size that makes the risk of the cancer showing up outside the chest higher than routine, they would be considered for getting the immunotherapy drug.
Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as newly diagnosed early stage NSCLC. It is FDA approved for advanced NSCLC, that is people who have already had some chemotherapy and their disease has worsened. Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer||Drug: Pembrolizumab Radiation: Stereotactic body radiotherapy||Early Phase 1|
The primary objective of this pilot safety study is to determine the tolerability and feasibility of administering pembrolizumab in the adjuvant setting following completion of definitive SBRT to the lung for patients with medically inoperable early stage NSCLC with tumors greater than 3 cm in diameter
- Distant metastases free survival (DMFS)
- Disease Free Survival (DFS)
- Overall survival (OS)
Study design including dose escalation / cohorts
This is an open-label, single arm feasibility study of lung SBRT followed 2 to 4 weeks after completion by the addition of pembrolizumab.
Eligible patients will have biopsy-confirmed T1b-T3N0M0 (stage IA-IIB) non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, or large cell/NSCLC NOS), performance status 0-2, deemed medically inoperable by a thoracic surgeon or pulmonologist, and no contraindications to pembrolizumab.
The primary endpoint for this study is safety and feasibility. For the first stage of this study, 8 patients will be enrolled. If >7 of the initial 8 patients complete the therapy without experiencing a Grade >3 pulmonary toxicity or any Grade >4 toxicity, an additional 7 patients will be enrolled for a total of 15 patients. If >2 of the original 8 patients (>25%) experience a Grade >3 pulmonary toxicity or any Grade >4 toxicity the trial will be closed and the study therapy will be considered too toxic. If >4 of 15 patients (>26.7%) experience a Grade >3 pulmonary toxicity or any Grade >4 toxicity, the study drug regimen will be deemed too toxic and unsafe. If >12 out of 15 patients complete the study without experiencing a Grade >3 pulmonary toxicity or any Grade >4 toxicity, the study drug regimen will be considered safe and feasible for further study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Adjuvant Pembrolizumab After Lung Stereotactic Body Radiotherapy (SBRT) for Medically Inoperable Early Stage Non-Small Cell Lung Cancer (NSCLC)|
|Actual Study Start Date :||February 19, 2019|
|Actual Primary Completion Date :||March 21, 2020|
|Actual Study Completion Date :||March 21, 2020|
Experimental: Pembrolizumab + Stereotactic Body Radiotherapy
Lung SBRT 50 Grays (Gy) in 5 fractions over 5-14 days, or 60 Gy in 3 fractions over 8-15 days.
Pembrolizumab 200mg IV every 21 days for 6 months
200mg IV every 21 days over 6 months
Other Name: Keytruda
Radiation: Stereotactic body radiotherapy
50 Grays (Gy) in 5 fractions over 5-14 days, or 60 Gy in 3 fractions over 8-14 days
- Percent of patients tolerant to study drug [ Time Frame: Up to 12 months ]<60% of patients being able to complete the scheduled doses of study drug without experiencing a Grade >3 pulmonary toxicity or any Grade >4 toxicity. Good tolerability had been defined as >90% of patients being able to complete the scheduled doses of study drug without experiencing a Grade >3 pulmonary toxicity or any Grade >4 toxicity.
- Duration of Distant metastases free survival (DMFS) [ Time Frame: Up to 5 years ]DMFS is defined as the time from initiation of study drug post-SBRT, until the first documented, confirmed distant-only [non local, non-regional nodal] progression of disease. DMFS will be measured and reported from the initiation of SBRT.
- Duration of Disease Free Survival [ Time Frame: Up to 5 years ]DFS is defined as the time from initiation of study drug post-SBRT that the patient survives without any signs or symptoms of that cancer. DFS will also be measured and reported from the initiation of SBRT.
- Duration of Overall Survival [ Time Frame: Up to 5 years ]OS will be measure from the initiation of SBRT until death.
- Duration of Local control [ Time Frame: Up to 5 years ]For the purpose of the study, local control will be defined as a complete response, partial response, or stable disease within the planning target volume. The duration of local control will be measured from the time of SBRT initiation.
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): NCT03574220
|Principal Investigator:||Gregory Videtic, MD||Cleveland Clinic, Case Comprehensive Cancer Center|