- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT03021993
Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
Phase II Trial of Nivolumab, an Anti-PD-1 Monoclonal Antibody, as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
연구 개요
상세 설명
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
-
-
South Carolina
-
Charleston, South Carolina, 미국, 29425
- Medical University of South Carolina
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
Newly diagnosed histologically proven locoregional OCSCC without evidence of distant metastases and a clinically determined T-stage of 2-4,
OR
Recurrent or persistent histologically proven locoregional OCSCC that was initially treated with surgery alone, and a clinically determined recurrent T-stage of 2-4.
Note - OCSCC includes the subsites of oral tongue, floor of mouth, gingiva, retromolar trigone, and buccal mucosa.
Note - To allow sufficient tumor tissue for the immunological analyses, patients with T-stage 1 OCSCC will be excluded
- Greater than or equal to 18 years of age
- ECOG performance status of 0 or 1
Screening labs must meet the following criteria and must be obtained within 14 days prior to registration:
- WBC > 2,000/µL
- Absolute Neutrophil Count >1,500/µL
- Platelets > 100 X 103/µL
- Hemoglobin > 9.0 g/dL
- Serum creatinine < 1.5 X ULN or CrCl > 40mL/min (if using the Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
- AST/ALT ≤ 3 x ULN
- Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Reproductive Status:
WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception with a failure rate of less than 1% per year for a period of 31 weeks after the last dose of investigational product.
WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 consecutive months of amenorrhea in a woman over 45.
Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to registration Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men, are not required to use contraception.
Exclusion Criteria:
- Prior immunotherapy or treatment with another anti PD 1 agent
- Prior chemotherapy including Cetuximab or radiation therapy
- Previous severe hypersensitivity reaction to another monoclonal antibody
- Women who are pregnant, lactating or expecting to conceive
- Men who are expecting to father children within the research period
- Known history of HIV or AIDS
- Positive test for HBV sAg or HCV antibody indicating acute or chronic infection
- Concomitant malignancies except cutaneous squamous cell carcinoma or basal cell carcinoma
- Unresectable primary tumor or regional disease; presence of distant metastases.
- History of pneumonitis or interstitial lung disease
- Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
- Presence of condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
---|---|
실험적: Nivolumab
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
|
Nivolumab will be administered on days 1, 15 and 29.
If disease has progressed at day 29, the subject will proceed to surgery.
If a response or stable disease is present after the third dose, a fourth dose will be given on day 43, then the subject will proceed to surgery.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Objective response rate using pathological response
기간: Time of surgery (day 36 or day 50)
|
Objective response rate: the sum of patients with either a pCR defined as no invasive and no in situ residuals present in the surgical specimen or partial pathologic response defined at least a 30% reduction in the size of the lesion in the surgical specimen.
The reduction in size will be determined by comparing the pretreatment clinical measurements (the sum of the greatest axial measurement obtained with calipers at the time of initial evaluation) with the final pathologic measurements.
|
Time of surgery (day 36 or day 50)
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Level of Treg cells in peripheral blood using immunostaining
기간: Day 1 and time of surgery (day 36 or day 50)
|
1. Levels of Treg cells in pre and post treatment peripheral blood will be evaluated using immunostaining for CD4 and flow cytometric analysis of Foxp3.
Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
|
Day 1 and time of surgery (day 36 or day 50)
|
Level of activated T-cells in peripheral blood
기간: Day 1 and time of surgery (day 36 or day 50)
|
2. Levels of activated T-cells in peripheral blood will be assessed using flow cytometry for expression of CD69, IFN γ, T-bet and ICOS in CD4+ cells.
Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
|
Day 1 and time of surgery (day 36 or day 50)
|
Level of immune stimulatory cytokines in peripheral blood
기간: Day 1 and time of surgery (day 36 or day 50)
|
3. Intratumoral immune activity assessed by levels of immune stimulatory cytokines including IL-2, IFN γ, and IL-12 or inhibitory cytokine, IL10 and TGF-beta, in OCSCC tumor lysates will be measured flow cytometrically by cytokine bead array.
Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
|
Day 1 and time of surgery (day 36 or day 50)
|
Expression of Th1 responses in CD4+ cells from peripheral blood
기간: Day 1 and time of surgery (day 36 or day 50)
|
Expression of IL-2 (Th1 responses) in CD4+ cells from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
|
Day 1 and time of surgery (day 36 or day 50)
|
Expression of Th2 responses in CD4+ cells from peripheral blood
기간: Day 1 and time of surgery (day 36 or day 50)
|
Expression of IIL 10 (Th2 responses) in CD4+ cells from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
|
Day 1 and time of surgery (day 36 or day 50)
|
Expression of CD8+ cells expressing granzyme B (ctolytic response) from peripheral blood
기간: Day 1 and time of surgery (day 36 or day 50)
|
2. Expression of CD8+ cells expressing granzyme B (cytolytic response) from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
|
Day 1 and time of surgery (day 36 or day 50)
|
공동 작업자 및 조사자
수사관
- 수석 연구원: David Neskey, MD, Medical University of South Carolina
간행물 및 유용한 링크
일반 간행물
- Knochelmann HM, Horton JD, Liu S, Armeson K, Kaczmar JM, Wyatt MM, Richardson MS, Lomeli SH, Xiong Y, Graboyes EM, Lentsch EJ, Hornig JD, Skoner J, Stalcup S, Spampinato MV, Garrett-Mayer E, O'Quinn EC, Timmers CD, Romeo MJ, Wrangle JM, Young MRI, Rubinstein MP, Day TA, Lo RS, Paulos CM, Neskey DM. Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma. Cell Rep Med. 2021 Oct 19;2(10):100426. doi: 10.1016/j.xcrm.2021.100426. eCollection 2021 Oct 19.
- Liu S, Knochelmann HM, Lomeli SH, Hong A, Richardson M, Yang Z, Lim RJ, Wang Y, Dumitras C, Krysan K, Timmers C, Romeo MJ, Krieg C, O'Quinn EC, Horton JD, Dubinett SM, Paulos CM, Neskey DM, Lo RS. Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma. Cell Rep Med. 2021 Oct 19;2(10):100411. doi: 10.1016/j.xcrm.2021.100411. eCollection 2021 Oct 19.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 102510
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
Oral Cavity SCC에 대한 임상 시험
-
Cancer Research UK종료됨인유두종바이러스(HPV) | Hypopharynx, Oropharynx, Oral Cavity, Supraglottis 또는 Larynx의 양성 또는 음성 두경부 편평 세포 암종(HNSCC)영국
-
International Agency for Research on CancerUniversity of Cambridge; Kilimanjaro Clinical Research Institute완전한
-
Novartis Pharmaceuticals모병진행성 EGFR 돌연변이 비소형폐암(NSCLC), KRAS G12-돌연변이 NSCLC, 식도 편평세포암(SCC), 두경부 SCC, 흑색종네덜란드, 대한민국, 스페인, 대만, 일본, 이탈리아, 캐나다, 미국, 싱가포르
-
Tufts Medical CenterDUSA Pharmaceuticals, Inc.완전한광선 구순염 | 편평세포암종(SCC-is) | 편평 세포 암종(SCC) | 광역동 요법(PDT) | 모스외과미국
-
Memorial Sloan Kettering Cancer Center모병
-
Rigshospitalet, Denmark아직 모집하지 않음
-
Seton Healthcare FamilyUniversity of Texas at Austin; Dell Medical School at The University of Texas at Austin빼는기저 세포 암종(BCC) | 편평 세포 암종(SCC)
Nivolumab에 대한 임상 시험
-
Universitätsklinikum KölnZKS Köln빼는자궁경부암 ≥ FIGO IIB 및/또는 림프절 전이
-
NYU Langone Health종료됨
-
Institut BergoniéBristol-Myers Squibb모병
-
St. Petersburg State Pavlov Medical University완전한
-
Stichting Hemato-Oncologie voor Volwassenen Nederland모집하지 않고 적극적으로림프종, B세포 | 비호지킨 림프종 | 고급 B 세포 림프종 | MYC 전위 | BCL-2 전좌네덜란드, 벨기에
-
M.D. Anderson Cancer Center모집하지 않고 적극적으로
-
Gruppo Oncologico del Nord-Ovest완전한
-
Amgen모병흑색종이탈리아, 스페인, 남아프리카, 일본, 세르비아, 보스니아 헤르체고비나, 미국, 아르헨티나, 칠레, 그루지야, 말레이시아, 대한민국, 프랑스, 독일, 네덜란드, 크로아티아, 태국, 브라질, 대만, 루마니아, 멕시코, 인도