Study of NGR-hTNF in Combination With Doxorubicin in Solid Tumors
2019년 9월 13일 업데이트: AGC Biologics S.p.A.
A Phase IB Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Solid Tumors
The main objective of the trial is to document the safety of the combination (escalation doses of NGR-hTNF, from 0.2 mcg/sqm to 1.6 mcg/sqm , with a fixed dose of doxorubicin, 75 mg/sqm).
Safety will be established by clinical and laboratory assessment according to National Cancer Institute Common Toxicity Criteria (NCI-CTC ).
연구 개요
상세 설명
This is a phase IB, open-label, non-randomized, dose-escalation study that will be conducted in sequential cohorts of patients. Three patients per each cohort are planned.
Patients, with advanced or metastatic solid tumor previously treated with a non cumulative dose of doxorubicin (<300 mg/sqm in order to allow an adequate number of cycles) or chemotherapy naïve will be enrolled.
연구 유형
중재적
등록 (실제)
15
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
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:
- Patients ≥18 years old with proven advanced or metastatic solid tumor not amenable to any clinical improvement by current standard treatments and previously treated with a non cumulative dose of anthracyclines (<300 mg/sqm) or chemotherapy naïve.
- Life expectancy more than 3 months.
- ECOG performance status 0 - 2.
- Normal cardiac function (left ventricular ejection fraction [LVEF] ≥55%) and absence of uncontrolled hypertension.
- Absence of any conditions involving hypervolemia and its consequences.
- Adequate baseline bone marrow, hepatic and renal function, defined as follows:
Neutrophils > 1.5 x 10^9/L and platelets >100 x 10^9/L Bilirubin < 1.5 x ULN AST and/or ALT < 2 x ULN Serum creatinine < 1.5 x ULN
Patients may have had prior therapy providing the following conditions are met:
- Chemo, radio, hormonal, immuno or anti-vascular therapy: wash-out period of 28 days.
- Surgery: wash-out period of 14 days.
- Patients must give written informed consent to participate in the study.
Exclusion Criteria:
- Concurrent anticancer therapy
- Patients must not receive any other investigational agents while on study
- Patients with a LVEF <55%
- New York Heart Association class III or IV cardiac disease
- Acute angina
- Patients with myocardial infarction within the last six (6) months
- Patient with significant peripheral vascular disease
- Thrombosis of main portal vein
- Previous signs of severe toxicity doxorubicin related
- Previous signs of cardiotoxicity doxorubicin related
- Patients previously treated with a cumulative dosage of anthracyclines ≥300 mg/m^2
- Clinical signs of CNS involvement
- Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
- Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
- Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
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: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: ㅏ
|
0.2, 0.4, 0.8 and 1.6 μg/m²as 60-minute intravenous infusion every 3 weeks
75 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion)
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Number of Adverse Events From Escalating Doses of NGR-hTNF in Combination With a Fixed Dose of Doxorubicin
기간: Through study completion, an average of 1 year
|
An Adverse Event (AE) is any untoward medical occurrence or experience in a patient or clinical investigation subject treated administered a pharmaceutical product and which does not necessarily have to have a casual relationship with this treatment.
An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
Through study completion, an average of 1 year
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Cmax)
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacokinetic profiles of NGR-hTNF and doxorubicin was conducted in 4 sequential cohorts of patients (Three patients per each cohort were planned).
The first 3 patients of the first cohort were treated with 0.2 μg/m2 of NGR-hTNF in combination with a suboptimal dose (minus 20%) of doxorubicin (60 mg/m2).Following 4 cohorts were treated with escalating dose of NGR-hTNF (0.2, 0.4, 0.8 and 1.6 μg/m2) in combination with a standard dose of doxorubicin (75 mg/m2):
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Tmax)
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacokinetic profiles of NGR-hTNF and doxorubicin was conducted in 4 sequential cohorts of patients (Three patients per each cohort were planned).
The first 3 patients of the first cohort were treated with 0.2 μg/m2 of NGR-hTNF in combination with a suboptimal dose (minus 20%) of doxorubicin (60 mg/m2).Following 4 cohorts were treated with escalating dose of NGR-hTNF (0.2, 0.4, 0.8 and 1.6 μg/m2) in combination with a standard dose of doxorubicin (75 mg/m2):
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (AUC0-t(Last))
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacokinetic profiles of NGR-hTNF and doxorubicin was conducted in 4 sequential cohorts of patients (Three patients per each cohort were planned).
The first 3 patients of the first cohort were treated with 0.2 μg/m2 of NGR-hTNF in combination with a suboptimal dose (minus 20%) of doxorubicin (60 mg/m2).Following 4 cohorts were treated with escalating dose of NGR-hTNF (0.2, 0.4, 0.8 and 1.6 μg/m2) in combination with a standard dose of doxorubicin (75 mg/m2):
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Emax)
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacodynamic calculations for sTNF-R1 and sTNF-R2 were performed on the plasma concentrations from which the baseline concentrations were subtracted (i.e. on positive and negative values).
At all doses, Emax, i.e. the maximal stimulatory effect, and tmax were estimated as the coordinates of the highest point of the plasma profile (y, x axis, respectively)
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Tmax)
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacodynamic calculations for sTNF-R1 and sTNF-R2 were performed on the plasma concentrations from which the baseline concentrations were subtracted (i.e. on positive and negative values).
At all doses, Emax, i.e. the maximal stimulatory effect, and tmax were estimated as the coordinates of the highest point of the plasma profile (y, x axis, respectively)
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (ARC)
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacodynamic calculations for sTNF-R1 and sTNF-R2 were performed on the plasma concentrations from which the baseline concentrations were subtracted (i.e. on positive and negative values).
At all doses, Emax, i.e. the maximal stimulatory effect, and tmax were estimated as the coordinates of the highest point of the plasma profile (y, x axis, respectively)
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Eav)
기간: prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
Pharmacodynamic calculations for sTNF-R1 and sTNF-R2 were performed on the plasma concentrations from which the baseline concentrations were subtracted (i.e. on positive and negative values).
At all doses, Emax, i.e. the maximal stimulatory effect, and tmax were estimated as the coordinates of the highest point of the plasma profile (y, x axis, respectively)
|
prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes
|
|
To Evaluate Phenotype Analysis and Adaptative Immune Response
기간: during the study
|
during the study
|
|
|
Signs of Anticancer Activity by Standard Imaging or Clinically; When Possible Tumor Response Will be Documented According to RECIST Criteria
기간: after the first 2 cycles(Follow-up 2) of treatment and then every 2 cycles (Follow-up 4,6..). In case of detection of a complete or partial response, a confirmation assessment must be performed ≥ 4 weeks after the first documentation of the response.
|
Response to treatment was assessed on a set of target lesions(TL) chosen before the 1st treatment administration, the list of TL must be reported on the initial measurement form before the start of treatment.
Lesions had to have clearly defined borders and initially were measured in at least one dimension, and had to be repeated at each evaluation of the disease by the same method.
Sum of the longest diameter (LD) was calculated as the baseline sum LD Complete Response(CR): Disappearance of all TL Partial Response(PR): At least a 30% decrease in the sum of the LD of TL, taking as reference the base line sum LD Progressive Disease(PD): At least a 20% increase in the sum of LD of TL, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
|
after the first 2 cycles(Follow-up 2) of treatment and then every 2 cycles (Follow-up 4,6..). In case of detection of a complete or partial response, a confirmation assessment must be performed ≥ 4 weeks after the first documentation of the response.
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Federico Caligaris Cappio, MD, Fondazione San Raffaele del Monte Tabor
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
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
2006년 2월 28일
기본 완료 (실제)
2007년 5월 8일
연구 완료 (실제)
2007년 5월 8일
연구 등록 날짜
최초 제출
2006년 3월 15일
QC 기준을 충족하는 최초 제출
2006년 3월 20일
처음 게시됨 (추정)
2006년 3월 21일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 10월 4일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 9월 13일
마지막으로 확인됨
2019년 9월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NGR003
- EUDRACT Number: 2005-004846-15
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