NCT06623656招募中2 期
Multicenter Randomized Phase II Trial of Neoadjuvant Radioimmunotherapy Versus Chemoimmunotherapy in Patients With Clinical Stages IB-III (N2) Non-small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Number of participants with pathological complete response (pCR)
研究概览
简要总结
The goal of this clinical trial is to learn if Cemiplimab with chemotherapy or Cemiplimab with stereotactic body radiation therapy (SBRT) works as treatment for stages IB, II, and III (N2) Non-Small Cell Lung Cancer (NSCLC).
Before surgery to remove their lung cancer, participants will take:
- Cemiplimab with chemotherapy (Arm A) every 3 weeks for up to 3 doses, OR
- Cemiplimab every 3 weeks for up to 3 doses with SBRT (Arm B). SBRT will be given on day 1 before taking cemiplimab, then SBRT alone on day 2 and day 3.
Four to 12 weeks following surgery, participants in both Arm A and Arm B will receive treatment with cemiplimab for one year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically or cytologically proven clinical stages IB (T2aN0), II, and III(N2) NSCLC (according to AJCC version 9) eligible for surgical resection with curative intent. Patients with 2 synchronous NSCLC are allowed.
- •Measurable disease, as defined by RECIST v1.
- •Known PD-L1 expression.
- •No known EGFR mutations or ALK fusions.
- •Written informed consent and HIPAA obtained from the subject prior to performing any protocol-related procedures.
- •Age > 18 years at time of study entry.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •No prior therapy for lung cancer
- •Adequate organ and bone marrow function as defined below:
- •Absolute neutrophil count (ANC) ≥1.5 x10(3)/uL
- •Platelets ≥75 x10(3)/uL
- •Hemoglobin ≥9 g/dL
- •Serum creatinine ≤1.5 X upper limit of normal (ULN) OR calculated CrCl ≥50 ml/min (using the Cockcroft-Gault formula).
- •Serum total bilirubin ≤1.5 X ULN, except in patients with clinically documented Gilbert's Syndrome where ≤3x the ULN is permitted
- •Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ≤3 X ULN
- •WOCBP* must have a negative serum (beta-hCG) at screening. a) *WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
- •- A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the CTFG guidance. Pregnancy testing and contraception are not required for women who are post-menopausal or with documented permanent sterilization.
- •b) Male study patients with WOCBP partners are required to use condoms unless they are vasectomized or practice sexual abstinence.
- •c) Vasectomized partner or vasectomized study patient must have received medical assessment of the surgical success.
- •d) Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and LAM are not acceptable methods of contraception. Female condom and male condom should not be used together.
- •WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and until 6 months after last treatment.
- •All men must agree not to donate sperm during the trial and for 6 months after receiving the last therapy dose.
排除标准
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of the study drug and of low potential risk for recurrence.
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- •Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ, in-situ urinary bladder cancer, treated localized prostate cancer, and ductal carcinoma in-situ.
- •Indolent hematological malignancies
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of cemiplimab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g.intra articular injection), corticosteroids or systemic corticosteroids at physiological doses which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- •2.a. Any condition that requires ongoing/continuous corticosteroid therapy (>10mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
- •3. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]. No active diverticulitis within the previous 3 months. The following are exceptions to this criterion:
- •Patients with vitiligo or alopecia
- •Patients with endocrinopathies (such as hypothyroidism or type 1 diabetes (e.g., following Hashimoto syndrome) stable on hormone replacement, or psoriasis that does not require systemic treatment.
- •Any chronic skin condition that does not require systemic therapy
- •Patients with childhood asthma that has resolved
- •Uncontrolled, intercurrent illness including, but not limited to: ongoing or active infection requiring antibiotics (exception is a brief (≤10 days) course of antibiotics to be completed before initiation of treatment), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the Investigator.
- •5. Interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that requires immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis is resolved ≥6 months prior to study treatment.
- •6. Receipt of a live vaccine within 30 days of the planned start of study medication.
- •Note: If a patient intends to receive a COVID-19 vaccine before the start of the study drug, participation in the study should be delayed at least 4 weeks after any COVID-19 vaccination. During the neoadjuvant treatment period, it is recommended to delay any COVID-19 vaccination or any other vaccination until patients have undergone radical surgery for the lung. A vaccine dose should not be administered less than 48 hours (ideally by at least one week) before or after study drug dosing.
- •7. Prior allogeneic stem cell transplant or solid organ transplant.
- •Uncontrolled HIV, active hepatitis B or C, or diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
- •Participants with known controlled HIV infection (undetectable viral load or HIV RNA PCR) and CD4 count above 250 either spontaneously or on a stable antiviral regimen are eligible. For these participants monitoring will be performed per local standards.
- •Participants with HBsAg positive who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving antiviral therapy for hepatitis B) are eligible. Participants with controlled infections must undergo periodic monitoring of HBV DNA. Participants must remain on antiviral therapy for at least 6 months beyond the last dose of investigational study medication.
- •Participants with HBsAg negative but total HBcAb positive are permitted with the following requirements: if HBV DNA PCR is above limit of detection at screening, initiate HBV antiviral therapy before study entry. If serum HBV DNA PCR is below the limit of detection, periodic monitoring of HBsAg must be performed.
- •Participants who are HCV Ab+ who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to successful prior course of anti-HCV therapy) are eligible.
- •9. Female patients who are pregnant or breastfeeding.
- •Sexually active men and WOCBP who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose. Highly effective contraceptive measures include:
- •stable use of combined (estrogen and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening
- •bilateral tubal ligation (occlusion)
- •vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study patient and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and or
- •sexual abstinence
- •Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
- •Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and LAM are not acceptable methods of contraception. Female condom and male condom should not be used together.
- •Sexually active men and their partners must use highly effective contraception as described above. Contraception is not required for men with documented vasectomy. Pregnancy testing and contraception are not required for women who are post-menopausal or with documented permanent sterilization.
- •Male participants: a male participants will be excluded from the study if that participant does not agree to use condoms or practice sexual abstinence, unless vasectomized, prior to the initial dose/start of study medication, during the study, and for at least 4 months after the last dose. Sperm donation is also prohibited during the same period. Vasectomy success must be confirmed by semen analysis.
- •11. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
- •12. Presence of cardiovascular disease, as defined by:
- •a. New York Heart Association heart failure classifications of Class II, III, or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication; or b. Transient ischemic attack or stroke within 1 year
- •Known hypersensitivity to the active substances or to any of the excipients.
- •14. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication.
研究组 & 干预措施
Cemiplimab with SBRT (Arm B)
Experimental
Before lung cancer surgery:
- Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles.
- SBRT on days 1, 2, and 3.
After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).
干预措施: Stereotactic body radiation therapy (Radiation)
Cemiplimab with chemotherapy (Arm A)
Experimental
Before lung cancer surgery:
- Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles.
- Platinum-based chemotherapy intravenously every 3 weeks up to 3 cycles.
After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).
干预措施: Platinum based chemotherapy (Drug)
Cemiplimab with chemotherapy (Arm A)
Experimental
Before lung cancer surgery:
- Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles.
- Platinum-based chemotherapy intravenously every 3 weeks up to 3 cycles.
After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).
干预措施: Cemiplimab (Drug)
Cemiplimab with SBRT (Arm B)
Experimental
Before lung cancer surgery:
- Cemiplimab 350 mg intravenously every 3 weeks up to 3 cycles.
- SBRT on days 1, 2, and 3.
After lung cancer surgery, cemiplimab 350 mg intravenously every 3 weeks for 4 treatments followed by 700 mg every 6 weeks for one year (11 treatments).
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Number of participants with pathological complete response (pCR)
时间窗: Surgical resection (Weeks 9-13).
pCR is defined as the absence of viable tumor in the tumor bed and the draining lymph nodes upon pathological review of the tissue.
次要结局
- Number of participants with Major Pathological Response (MPR)(Surgical resection (Weeks 9-13).)
- Number of participants with neoadjuvant treatment-related adverse events as assessed by CTCAE v5.0(From cemiplimab with chemotherapy and cemiplimab with SBRT treatment start date (Day 1) to prior to surgical resection (Weeks 9-13).)
- Surgical delay, mean/standard deviation(From the date of the last dose of neoadjuvant cemiplimab treatment (Week 7) to surgical resection (Weeks 9-13).)
- Number of participants with minimal access surgery(Time of surgical resection (Week 9-13), after the last preoperative dose of cemiplimab.)
- Change in number of participants with distant recurrence(From cemiplimab with chemotherapy and cemiplimab with SBRT treatment start date (Day 1) to recurrence (Every 6 months for 3 years, then yearly for year 4-5).)
- Change in number of participants with local recurrence(From cemiplimab with chemotherapy and cemiplimab with SBRT treatment start date (Day 1) to recurrence (Every 6 months for 3 years, then yearly for year 4-5).)
- Change from baseline in health-related quality of life, as measured by the European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire (EORTC QLQ-C30)(From baseline (Day 1), Post Treatment (Weeks 9-10), to 6 months post operatively.)
- Change from baseline in health-related quality of life, as measured by the European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire (EORTC QLQ-LC13)(Baseline (Day 1), Post Treatment (Weeks 9-10), to 6 months post operatively.)
- Event Free Survival (EFS) in months(From randomization (day 1) up to 2 years.)
- Number of days spent in the ICU (Intensive care unit)(From the time of admission (Week 9-13) to the ICU (approximately 1 day after surgical resection) to discharge (approximately 2-5 days after surgical resection))
- Number of participants with surgical adverse events as assessed by CTCAE v5.0(From the time of surgical resection (Weeks 9-13) until hospital discharge, approximately 2-5 days after surgical resection.)
- Number of days spent in the hospital(From the date of surgery (Weeks 9-13) to discharge from the hospital (approximately 2-5 days after surgical resection))
- Number of participants with negative surgical resection margins (R-0)(Time of surgical resection (Weeks 9-13), after the last preoperative dose of cemiplimab.)
- Progression Free Survival (PFS) in months(From randomization (day 1) up to 2 years.)
研究者
研究点 (2)
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