A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors
2020년 2월 10일 업데이트: Hoffmann-La Roche
An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors
This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab.
Part I of the study is subdivided into parts IA and IB.
Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab.
Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.
연구 개요
연구 유형
중재적
등록 (실제)
228
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Amsterdam, 네덜란드, 1066 CX
- Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie
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København Ø, 덴마크, 2100
- Rigshospitalet; Onkologisk Klinik
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California
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Santa Monica, California, 미국, 90404
- UCLA Cancer Center
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Stanford, California, 미국, 94305
- Stanford Comprehensive Cancer Center
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Colorado
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Aurora, Colorado, 미국, 80045
- University of Colorado
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Connecticut
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New Haven, Connecticut, 미국, 06510
- Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy
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Massachusetts
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Boston, Massachusetts, 미국, 02215
- Dana Farber Can Ins
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New York
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New York, New York, 미국, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, 미국, 10032
- Columbia Univ Med Ctr
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North Carolina
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Durham, North Carolina, 미국, 27710
- Duke Cancer Center
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South Carolina
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Charleston, South Carolina, 미국, 29425
- Medical University of South Carolina
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Tennessee
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Germantown, Tennessee, 미국, 38138
- Sarah Cannon Cancer Center
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Texas
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Houston, Texas, 미국, 77030
- MD Anderson Cancer Center
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Barcelona, 스페인, 08003
- Hospital del Mar; Servicio de Oncologia
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Barcelona, 스페인, 08035
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
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Madrid, 스페인, 28041
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
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Madrid, 스페인, 28040
- START Madrid-FJD, Hospital Fundación Jiménez Díaz
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Madrid, 스페인, 28050
- START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
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Navarra
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Pamplona, Navarra, 스페인, 31008
- Clinica Universitaria de Navarra; Servicio de Oncologia
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Campania
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Napoli, Campania, 이탈리아, 80131
- IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative
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Toscana
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Siena, Toscana, 이탈리아, 53100
- Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
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Ontario
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Toronto, Ontario, 캐나다, M5G 1Z5
- Princess Margaret Cancer Center
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Lyon, 프랑스, 69373
- Centre Leon Berard; Departement Oncologie Medicale
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Villejuif, 프랑스, 94805
- Institut Gustave Roussy
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria
- Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
- Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)
- Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels </= 2.5 ULN (upper limit of normal)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade </= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy
- Adequate hematological, liver, and renal function
- Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years)
- Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol
- Participants with non-colorectal cancer should have confirmed CEA expression in tumor tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the result is not required for participant selection
Exclusion Criteria
- Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to enrollment
- Leptomeningeal disease
- Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated
- Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
- Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results
- Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment
- Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
- Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)
- Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis
- Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
- Known history of autoimmune disease as defined in the protocol
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Participants with bilateral lung lesions and dyspnea and/or oxygen saturation level (SaO2) less than 92% (at rest, room air and exertion) or participants with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 less than 92% (at rest, room air and exertion) at baseline
- Pregnant or breast-feeding
- Known hypersensitivity to any of the components of RO6958688 and atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Investigational therapy (defined as treatment for which there is no regulatory authority approved indication) or last dose of prior immunotherapies within 28 days prior to Cycle 1 Day 1. Participants previously treated with anti-programmed death-ligand 1 (PD-L1), or anti-PD-1 are excluded
- Last dose of any approved anti-cancer therapy within 28 days prior to the first RO6958688 infusion
- Prior systemic corticosteroids greater than 10mg prednisone (or equivalent) within 14 days of Cycle 1 Day 1. Inhaled and/or topical steroids are permitted
- Expected need for regular immunosuppressive therapy
- Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of limited-field palliative radiotherapy
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Dose-Escalation (Part IA): RO6958688 + Atezolizumab
Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W).
RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
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Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
다른 이름들:
RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
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실험적: Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab
Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first. |
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
다른 이름들:
RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
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용량 제한 독성(DLT)이 있는 참가자의 비율
기간: 1일차부터 21일차까지
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1일차부터 21일차까지
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Number of Participants with Adverse Events (AEs)
기간: Baseline up to 60 months
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Baseline up to 60 months
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Maximum-Tolerated Dose (MTD) of RO6958688
기간: Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
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Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
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Recommended Phase II Dose (RP2D) of RO6958688
기간: Day 1 up to 60 months
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Day 1 up to 60 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: Volume of Distribution at Steady State (Vss) of RO6958688
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: Maximum Serum Concentration (Cmax) of RO6958688
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: Clearance (CL) of RO6958688
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: AUC of Atezolizumab
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: Vss of Atezolizumab
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: Cmax of Atezolizumab
기간: Baseline up to 60 months
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Baseline up to 60 months
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PK: CL of Atezolizumab
기간: Baseline up to 60 months
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Baseline up to 60 months
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Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
기간: Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
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Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
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Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])
기간: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST
기간: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST
기간: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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Duration of Response (DOR) as Assessed Using RECIST
기간: From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
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Progression-Free Survival (PFS) according to RECIST V1.1
기간: From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
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Overall Survival (OS)
기간: From first study treatment to death from any cause (up to 60 months)
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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From first study treatment to death from any cause (up to 60 months)
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Best Overall Response (BOR)
기간: Baseline up to 60 months
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Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
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Baseline up to 60 months
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
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연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2016년 1월 7일
기본 완료 (실제)
2020년 1월 13일
연구 완료 (실제)
2020년 1월 13일
연구 등록 날짜
최초 제출
2016년 1월 6일
QC 기준을 충족하는 최초 제출
2016년 1월 6일
처음 게시됨 (추정)
2016년 1월 8일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2020년 2월 12일
QC 기준을 충족하는 마지막 업데이트 제출
2020년 2월 10일
마지막으로 확인됨
2020년 2월 1일
추가 정보
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. .