이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

돌연변이 KRAS - 췌장암 발병 위험이 높은 환자를 위한 표적화된 긴 펩타이드 백신

This Phase 1 study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine with poly-ICLC adjuvant for patients who have been identified to be at risk of developing pancreatic cancer.

연구 개요

상태

모집하지 않고 적극적으로

정황

개입 / 치료

상세 설명

This study will evaluate safety and the immune response to pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with poly-ICLC adjuvant. The primary endpoints of this study are to determine the safety of administering the KRAS peptide vaccine with poly-ICLC adjuvant and to assess the maximal percent change of IFN-γ-producing mutant-KRAS-specific T cells per patient at any time after vaccination. Twenty five patients will be enrolled to achieve 20 evaluable patients for Cohort A. Twelve patients will be enrolled to achieve 10 evaluable patients for Cohort B.

For all patients, the study will consist of a screening phase, treatment phase, and a follow-up visit. All subjects will have the option remaining on study with annual follow-up visits that begin approximately one year after the last vaccine dose and continue annually thereafter until study closure.

연구 유형

중재적

등록 (실제)

31

단계

  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

    • Maryland
      • Baltimore, Maryland, 미국, 21231
        • Sidney Kimmel Comprehensive Cancer Center

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

40년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

예

연구 대상 성별

모두

설명

Inclusion Criteria:

Cohort A: Must fall into one of the three categories defined as high risk of developing pancreatic cancer and are undergoing pancreatic surveillance AND 2) have documented radiographic evidence of a pancreatic abnormality such as a pancreatic cyst.

  • High Risk Group 1 (familial pancreatic cancer relatives):

    • >/=55 years old or 10 years younger than the age of youngest relative with pancreatic cancer, and
    • Come from a family with 2 or more members with a history of pancreatic cancer (2 of which have a first-degree relationship consistent with familial pancreatic cancer), and
    • Have a first-degree relationship with at least one of the relatives with pancreatic cancer.
    • If there are 2 or more affected blood relatives, at least 1 must be a first-degree relative of the individual being screened.
  • High Risk Group 2 (Germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of ~10% or higher):

    • >/=40 years old and the Patient is a carrier of FAMMM (p16/CDKN2A) mutation regardless of family pancreas cancer history.

OR

  • >/= 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and the Patient is a carrier of a known BRCA2, ATM, PALB2 mutation.

  • Persons with known genetic mutation should have proof of mutation status. Those who had research-related genetic testing must have confirmation by a clinical CLIA-certified laboratory.

    o High Risk Group 3 (Germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of ~5%):

  • >/= 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and

  • The patient is a carrier of a known, BRCA1, or HNPCC (hereditary non-polyposis colorectal cancer or Lynch syndrome, hMLH1, hMSH2, PMS1, hMSH6, EpCAM) gene mutation, and there is > 1 pancreatic cancer in the family, one of whom is a first- or second-degree relative of the subject to be screened.

  • Persons with known genetic mutation should have proof of mutation status. Those who had research-related genetic testing must have confirmation by a clinical CLIA-certified laboratory.

  • Cohort A: Patients must have a pancreatic imaging abnormality that is being followed by pancreatic imaging surveillance (EUS and/or MRI and /or CT), such as a pancreatic cyst consistent with an IPMN or parenchymal abnormalities consistent with PanIN.

    • Cohort B: Patients must have clinical, radiographic, or histologic evidence of pancreatic cystic neoplasm with high-risk features warranting surgical resection per the discretion of the treating hepatobiliary surgeon.
    • Cohort B: Patients must have cystic fluid testing that demonstrates the presence of one of the six KRAS mutations included in the study vaccine.
  • Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.

  • Ability to understand and willingness to sign a written informed consent document.

  • Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.

  • Men must use acceptable form of birth control while on study.

Exclusion Criteria:

  • If expected to require any other form of systemic or localized antineoplastic therapy while on study.

  • Within 4 weeks prior to first dose of study drug.

    o Any systemic or topical corticosteroids at immunosuppressive agents.

  • Within 4 weeks prior to first dose of study drug.

    • Any investigational device.
    • Has received a live vaccine.
    • Received any allergen hyposensitization therapy.
    • Any major surgery.
  • Infection with HIV or hepatitis B or C.

  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements monoclonal antibody.

  • Has a diagnosis of immunodeficiency.

  • Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.

  • Unwilling or unable to follow the study schedule for any reason.

  • Are pregnant or breastfeeding.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 방지
  • 할당: 무작위화되지 않음
  • 중재 모델: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Cohort A: Patients at high risk of developing pancreatic cancer.

Patients will include those who have undergone pancreatic imaging with MRI or CT or EUS and found to have one or more pancreatic imaging abnormalities such as a pancreatic cyst consistent with an intraductal papillary mucinous neoplasm (IPMN) or parenchymal changes consistent with pancreatic intraepithelial neoplasia (PanIN). additionally patients with:

  1. familial pancreatic cancer relatives
  2. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of ~10% or higher
  3. germline mutation carriers with an estimated lifetime risk of pancreatic cancer of ~5%, all detailed in Section 3.1.1. These patients must also (as defined in Section 3.1.2).
  1. KRAS peptide vaccine with poly-ICLC adjuvant will be administered on Prime week 1, 3, and 5. Boost vaccinations with will be administered at week 13. All subjects will return to the study site approximately 28 days (+ 7 days) after the last vaccination for an End of Treatment (EOT) and safety evaluation.
  2. Drug: up to 1.8 mg KRAS peptide vaccine + 0.5mg Poly-ICLC
다른 이름들:
  • Hiltonol®(폴리-ICLC)
실험적: Cohort B: Patients must have evidence of a pancreatic cystic neoplasm

Patients must have clinical, radiographic, or histologic evidence of a pancreatic cystic neoplasm with high-risk features warranting surgical resection per the discretion of the treating hepatobiliary surgeon. In addition, cyst fluid analysis must demonstrate the presence of one of the six KRAS mutations included in the study vaccine. Germline mutation testing or a positive family history of pancreatic cancer is not required for enrollment in Cohort B.

Patients will receive KRAS peptide vaccine with poly-ICLC adjuvant as two prime vaccinations on weeks 1 and 2. Surgery is considered standard of care. Surgery will occur at the discretion of the treating hepatobiliary surgeon and is not dictated by this protocol. Subjects will return to the study site approximately at week 4 (+ 7 days) for a safety evaluation prior to surgery. Subjects will have an End of Treatment (EOT) visit at study Week 8 (+ 7 days).

다른 이름들:
  • Hiltonol®(폴리-ICLC)

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Number of participants experiencing study drug-related toxicities
기간: 1.5 years

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

1.5 years
Maximal percentage of change of interferon (IFN-γ) producing mutant-KRAS-specific CD8 and CD4 T cells
기간: 17 weeks

Maximal percent change per patient within 17 weeks after vaccination.

17 weeks

2차 결과 측정

결과 측정
측정값 설명
기간
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5 weeks.
기간: Baseline, 5 weeks (Cohort A)

Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5 weeks after vaccination compared to pre-vaccination baseline.

Baseline, 5 weeks (Cohort A)
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 13 weeks.
기간: Baseline, 13 weeks (Cohort A)

Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 13 weeks after vaccination compared to pre-vaccination baseline.

Baseline, 13 weeks (Cohort A)
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 17 weeks.
기간: Baseline,17 weeks (Cohort A)

Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 17 (EOT) weeks after vaccination compared to pre-vaccination baseline.

Baseline,17 weeks (Cohort A)

기타 결과 측정

결과 측정
측정값 설명
기간
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 1 weeks.
기간: Baseline, 1 week (Cohort B)

Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 5 weeks after vaccination compared to pre-vaccination baseline.

Baseline, 1 week (Cohort B)
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 4 weeks.
기간: Baseline, 4 weeks (Cohort B)

Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 13 weeks after vaccination compared to pre-vaccination baseline.

Baseline, 4 weeks (Cohort B)
Fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 8 weeks.
기간: Baseline, 8 weeks (Cohort B)

Evaluated by the fold change in interferon-producing mutant-KRAS-specific CD8 and CD4 T cells at 17 (EOT) weeks after vaccination compared to pre-vaccination baseline.

Baseline, 8 weeks (Cohort B)

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

협력자

수사관

  • 수석 연구원: Nilofer Azad, MD, Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins Medical Institution

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)

2022년 4월 11일

기본 완료 (추정된)

2027년 10월 1일

연구 완료 (추정된)

2031년 5월 1일

연구 등록 날짜

최초 제출

2021년 8월 18일

QC 기준을 충족하는 최초 제출

2021년 8월 18일

처음 게시됨 (실제)

2021년 8월 19일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 10월 6일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 10월 5일

마지막으로 확인됨

2026년 10월 1일

추가 정보

이 연구와 관련된 용어

기타 연구 ID 번호

  • J2177
  • IRB00288752 (기타 식별자: Johns Hopkins Medical Institution)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

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. .