- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT03084926
First-in-human Study to Investigate Safety, Blood Levels and Activity of MP0274 in Cancer Patients With HER2-positive Solid Tumors
A Phase 1, First-in-human, Single-arm, Multi-center, Open-label, Repeated-Dose, Dose-escalation Study to Assess Safety, Tolerability and Pharmacokinetics of MP0274 in Patients With Advanced HER2-positive Solid Tumors
Přehled studie
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
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Frankfurt, Německo
- Study Site Frankfurt
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Heidelberg, Německo
- Study Site Heidelberg
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Cambridge, Spojené království
- Study Site Cambridge
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Saint Gallen
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St. Gallen, Saint Gallen, Švýcarsko
- Study Site St. Gallen
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
INCLUSION CRITERIA
- Have signed and dated written informed consent prior to performing any study procedure, including screening
- Are ≥ 18 years old on the day of signing informed consent
Have histologically confirmed and documented HER2 positive solid tumor malignancy that is unresectable, locally advanced, or metastatic with progression
- Part A of study: Assessed on tumor tissue from most recent biopsy
- Part B of study: Assessed on the latest tumor biopsy material for HER2 and other scheduled tissue testing from within 6 months before entry into the study Part A and B: Tumor tissue must be made available to the Sponsor for central testing
Have received standard, available therapies approved for their cancer, unless they are unsuitable for these treatments (incurable disease)
- Have documented PD on most recent systemic antitumor treatment
- Disease assessment Part A: Evaluable Disease (disease that cannot be measured directly by the size of the tumor but can be evaluated by other methods) or Measurable Disease according to RECIST v1.1 (in case of skin lesions, documentation by color photography including a ruler to estimate the size of the lesion is acceptable) Part B: Measurable Disease as per RECIST 1.1
- Have an ECOG PS of 0-2
Have adequate hematological function prior to first scheduled dose, defined as:
- Absolute neutrophil count ≥ 1500 cells/µL
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 75,000/µL
- Prothrombin time or activated partial thromboplastin (aPTT) time ≤ 1.5 × upper limit of normal (ULN)
Adequate renal function prior to first scheduled dose, defined as either:
- Serum creatinine ≤ 1.5 mg/dL Or
- Serum creatinine clearance ≥ 40 mL/min (by Cockcroft-Gault equation)
- Values for potassium, calcium and magnesium must be within normal ranges. Patients may receive supplements to meet these requirements
Adequate hepatic function
- Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5 × ULN, or if known hepatic metastases ≤5 × ULN
- Total bilirubin ≤ 1.5 × ULN
- Serum albumin concentration ≥ 30 g/L
Highly effective contraception, for both women and men, is ensured:
- Female patients must be either post-menopausal women, or highly effective contraceptive measures must be ensured. Menopause is defined as occurring 12 months after last menstrual period
- Pre-menopausal or menopausal women who fulfill the following conditions: They must have had a prior hysterectomy or be using 2 highly effective methods of contraception (i.e. with failure rates less than 1% per year when used consistently and correctly, e.g. established use of oral, injected or implanted hormonal methods of contraception; intrauterine device; condom with spermicidal foam or gel or film or cream or suppository), from the time of screening through the whole treatment phase of the study, and for at least 3 months following the completion of the last MP0274 administration
- Men capable of fathering a child must agree to use barrier contraception (combination of a condom and spermicide) or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, during the treatment phase of the study and for at least 3 months following the completion of the last MP0274 infusion
- Men capable of fathering a child must refrain from donating sperm for duration of study and for at least 4 months after last administration of MP0274
- Female patients of child-bearing potential must have a negative serum pregnancy test result at screening
EXCLUSION CRITERIA
Patients will be ineligible if 1 or more of the following statements are applicable:
- Hematological malignancies or other second primary malignancy, that is currently clinically significant or requires active intervention
- Known brain metastases that are clinically unstable despite treatment with anticonvulsives and/or corticosteroids for at least 8 weeks prior to first scheduled dose of MP0274
Receipt of any of the following previous anti-tumor treatments:
- Cumulative doxorubicin ≥ 360 mg/m2
- Cumulative epirubicin ≥ 720 mg/m2
- Lapatinib within 7 days of scheduled dosing Day 1
- Chemotherapy, trastuzumab, or trastuzumab emtansine, other biologics, targeted or experimental therapy within 4 weeks of scheduled dosing Day 1, and for pertuzumab within 12 weeks
- Nitrosoureas or mitomycin C chemotherapy within 6 weeks of scheduled dosing Day 1
- Hormonal (e.g. tamoxifen) or aromatase inhibitor therapy within 8 weeks prior to first dose MP0274, except if no change in dose or schedule 8 weeks prior to first scheduled dose MP0274
- Newly initiated therapy with bisphosphonate or receptor activator of nuclear kappa-B ligand (RANKL)-therapy within 8 weeks prior to first scheduled dose MP0274. If stable on dosing schedule for more than 8 weeks prior to first scheduled dose MP0274 these therapies are allowed. However, no new therapy with bisphosphonate/RANKL is allowed during the course of the study
- Received concurrent radiation therapy within 4 weeks prior to first scheduled dose MP0274. Local radiation therapy to painful bone metastases following institutional standard practice for palliative radiotherapy to bone metastases is allowed
- Presence of neuropathy as residual toxicity after prior anti-tumor therapy Grade > 2
Any of the following cardiac exclusion criteria:
- Known history of symptomatic congestive heart failure
- LVEF < 55%, assessed by 2-dimensional echocardiography (2D Echo)
- Known absolute decrease in LVEF of ≥ 15 absolute percentage points on prior anti-HER2 therapy, even if asymptomatic
- High-risk uncontrolled arrhythmias such as resting bradycardia with a heart rate < 55 beat/min, atrial tachycardia with a resting heart rate > 100 beats/min, clinically significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular (AV) block (second degree AV-block Type 2 or third degree AV-block), implantable pacemaker or defibrillator, family history of long QT syndrome
- QTc prolongation > Grade 1 (> 480 ms) at screening measured on 2 separate ECGs at least 10 min apart
- Angina pectoris requiring anti-angina medication
- History of cardiac infarction or evidence of transmural infarction on ECG
- Troponin ≥ Grade 1 (above the upper limit of normal)
- Both, CK > 2.5-fold ULN range and CK-MB > 6% of total CK at screening
- Coronary artery bypass graft, coronary artery angioplasty or stent placement within 12 months before screening
- Clinically significant valvular heart disease
- Known hyperthyroidism
- Hypertension which is not controlled to systolic < 160 mm Hg and diastolic < 100 mm Hg
Clinically significant lung disorders such as:
- Non-malignant interstitial lung disease or pneumonitis
- Dyspnea of any cause requiring supplemental oxygen therapy and dyspnea at rest due to complications of advanced malignancy and co-morbidities
- History of allogeneic bone marrow or stem cell transplant
- Known positivity for human immunodeficiency virus (HIV) or history of HIV
Patients having active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HbsAg] test at screening) or active hepatitis C at screening
o Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HbcAb] and absence of HbsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
- Any active infection requiring the use of parenteral anti-microbial agents or that is > Grade 2
- Unable or unwilling to comply with all study requirements for clinical visits, examinations, tests, and procedures
- Concurrent participation in another clinical study involving treatment with the IMP and/or safety follow-up post treatment with IMP (Long-term Survival Follow-up is permitted)
- Previous treatment with MP0274 (to exclude re-entering the study)
- Hypersensitivity to any of the excipients of the finished drug MP0274
- Patients who are pregnant or breast-feeding
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: MP0274
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Intravenous infusion of MP0274 as single agent at four planned dose levels, every three weeks until progressive disease, unacceptable toxicity or patient withdrawal for other reasons
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Incidence and severity of adverse events
Časové okno: from first infusion to end-of-study visit, up to 12 months
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Number and grading according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
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from first infusion to end-of-study visit, up to 12 months
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
---|---|---|
Pharmacokinetics of MP0274
Časové okno: from first infusion to end-of-study visit, up to 12 months
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Serum concentration-time profile of MP0274
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from first infusion to end-of-study visit, up to 12 months
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Preliminary assessment of anti-tumor activity of MP0274
Časové okno: from first infusion to end-of-study visit, up to 12 months
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Efficacy evaluation based on Response Evaluation Criteria in Solid Tumors (RECIST)
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from first infusion to end-of-study visit, up to 12 months
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Incidence of anti-drug-antibodies
Časové okno: from first infusion to end-of-study visit, up to 12 months
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Serum concentration-time profile of anti-drug antibodies
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from first infusion to end-of-study visit, up to 12 months
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další identifikační čísla studie
- MP0274-CP101
- 2016-004712-36 (Číslo EudraCT)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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