Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
A Phase 1b Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder
연구 개요
상태
상세 설명
Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. Reovirus has been shown to replicate selectively in Ras-transformed cells causing cell lysis. Activating mutations in Ras or mutations in oncogenes signaling through the Ras pathway may occur in as many as 80% of human tumors. The specificity of the reovirus for Ras-transformed cells, coupled with its relatively nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate.
This is an open-label study of intratumoral REOLYSIN® in combination with standard of care neoadjuvant cisplatin/gemcitabine in patients with histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph node involvement (N1-2) in Stage III and IV with no distant metastases (M0) and no prior systemic therapy for bladder cancer.
Treatment with intratumoral REOLYSIN® and chemotherapy is planned for 3 cycles followed by radical cystectomy or until unacceptable toxicity or another discontinuation criterion is met.
Two sequential treatment cohorts will be enrolled.
Patients in Cohort 1 will receive intratumoral REOLYSIN® on Cycle 1 Day 1, then 7-14 days later patients will receive intratumoral REOLYSIN® on Cycle 2 Day 1 plus intravenous neoadjuvant chemotherapy for 2 cycles (every 3 weeks) starting from Cycle 2 Day 2 followed by radical cystectomy. Three patients will be enrolled in this cohort. If there is a Dose Limiting Toxicity the cohort will be expanded to an additional 3 patients.
Upon completion of Cohort 1, Cohort 2 will be open to enrollment of 3 patients to receive 3 cycles of standard neoadjuvant chemotherapy on Day 1 and Day 8 of each cycle and intratumoral REOLYSIN® on Day 2 of each cycle (every 3 weeks). If there is a Dose Limiting Toxicity the cohort will be expanded to an additional 3 patients.
An Expansion Cohort will follow with up to 12 patients to be enrolled following either Cohort 1 or Cohort 2 treatment regimen based on the results of Cohort 1 and Cohort 2.
연구 유형
단계
- 1단계
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph nodes involvement (N1-2) in Stage III and IV (M0).
- ECOG performance status ≤2.
- Adequate liver function with a bilirubin within normal limits. Transaminases up to 3 x ULN (Grade 1) and alkaline phosphatase may be up to 2.5 x ULN (Grade 1).
- Adequate bone marrow function, as defined by neutrophils count of ≥1,500/mm3, and platelet count ≥100,000/ mm3.
- Adequate renal function (serum creatinine ≤1.5 times the ULN).
- Negative pregnancy test and reliable and appropriate contraceptive method during the study for a woman of childbearing potential. All female patients of childbearing age and all male patients with partners of childbearing age should use a reliable method of contraception, such as the barrier method, throughout the study and for 60 days after last treatment.
- Informed of the investigational nature of this study and must sign a written informed consent in accordance with institutional and federal guidelines.
Exclusion Criteria:
- Received any prior therapy for invasive bladder cancer including surgery, radiation therapy, chemotherapy or any other systemic anti-cancer therapy (prior intravesical therapy for non-invasive bladder cancer is acceptable including intravesical BCG and/or mitomycin and interferon).
- Evidence of lymph nodes or other metastatic disease beyond the pelvis (N3 and/or M1).
- Pre-existing immunosuppressive or connective tissue disorders that require immune suppressive drugs.
- History of HIV or active hepatitis.
- Any serious concurrent illness including; but not limited to, unstable angina pectoris, uncompensated congestive cardiac failure; myocardial infarct in the previous 6 months; cardiac arrhythmias or psychiatric illness that would limit compliance with study requirements.
- Pregnant or lactating.
- A history of hypersensitivity to gemcitabine and cisplatin or any component of the formulation.
- A prior malignancy, other than non-melanoma skin cancer, unless they have completed therapy at least 5 years prior to start of study and have no evidence of recurrent or residual disease.
- Unwilling or unable to sign informed consent document.
- In social situations that would limit compliance with study requirements.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Incidence of Treatment-Emergent Adverse Events
기간: During treatment and up to 28 days after treatment
|
Nature, frequency, severity and timing of Adverse Events.
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During treatment and up to 28 days after treatment
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Pre- and post-treatment biopsies will be evaluated for tumor viability, percentage of necrosis, reovirus replication and tumor infiltration of immune cells and expression of PD-1 and PD-L1
기간: Assessed at surgery conducted following 3 3-week study treatment cycles
|
Assessed at surgery conducted following 3 3-week study treatment cycles
|
2차 결과 측정
결과 측정 |
기간 |
|---|---|
|
Time to Treatment Failure (TTF)
기간: By medical chart review until disease reoccurrence or 2 years from surgery, whichever occurs first first.
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By medical chart review until disease reoccurrence or 2 years from surgery, whichever occurs first first.
|
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Disease Free Survival (DFS)
기간: By medical chart review until disease reoccurrence or death or 2 years from surgery, whichever occurs first.
|
By medical chart review until disease reoccurrence or death or 2 years from surgery, whichever occurs first.
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (예상)
기본 완료 (예상)
연구 완료 (예상)
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
- REO 023
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
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