Phase 3 study of SBRT ± pembrolizumab for participants with unresected Stage I or II NSCLC
- Conditions
- on-Small Cell Lung Cancer Stage I or IIMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004320-11-NL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 530
A participant will be eligible for inclusion in the study if the participant:
1. Has previously untreated NSCLC diagnosed by histology or cytology and confirmed as Stage I or II (T1 to limited T3, N0, M0) NSCLC (AJCC 8th edition) by chest CT and PET scan. Prospective participants with mediastinal lymph nodes measured on chest CT as >1 cm in the short axis or PET avid lymph nodes may be eligible if the lymph node(s) in question is biopsied and is histologically benign.
2. Cannot undergo thoracic surgery due to existing medical illness(es) or anatomically unresectable tumor as determined by the site’s multidisciplinary tumor board. Medically operable participants who decide to treat with SBRT as definitive therapy rather than surgery are also eligible, if patient’s unwillingness to undergo surgical resection is clearly documented. If there is no tumor board, then this decision will be made by the investigator in consultation with a thoracic surgeon and a radiation oncologist if the investigator is not a radiation oncologist.
3. Has an ECOG performance status of 0, 1, or 2.
4. Is able to receive SBRT and does not have an ultra-centrally located tumor as defined in the radiation manual.
5. Has adequate organ function. Specimens must be collected within 7 days prior to the start of study intervention.
6. Is male or female =18 years of age, at the time of signing the informed consent.
MALE PARTICIPANTS
7. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of radiotherapy:
• Refrain from donating sperm
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent
OR
• Must agree to use contraception, unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site
personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP (see Section 10.5) who is not currently pregnant. Note: Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
- Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above,
the local label requirements are to be followed.
FEMALE PARTICIPANTS
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in rela
The participant must be excluded from the study if the participant:
1. Is a WOCBP who has a positive highly sensitive pregnancy test within 24 hours for urine or within 72 hours for serum prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
3. Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or breast. Participants receiving radiotherapy to the contralateral breast at least 5 years prior to randomization may still be eligible.
4. Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Refer to protocol for information on COVID-19 vaccine.
5. Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
7. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. A prior NSCLC that occurred and was treated curatively at least 2 years prior to the date of the current diagnosis would be considered a separate primary lung cancer, and therefore an additional malignancy.
8. Has a known hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
9. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
10. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
11. Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg thyroxine, insulin, or physiologic corticosteroid).
12. Has an active infection requiring systemic therapy.
13. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
14. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). No TB testing is required unless mandated by local health authority.
15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
16. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
17. Is pregnant or breastfeeding or expecting to conceive within the projected
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method