Estudio de fase I/II multicéntrico, abierto, de escalada de dosis, para evaluar la seguridad, farmacocinética y actividad de RO5083945, un anticuerpo glico-modificado anti-EGFR, en pacientes con tumores sólidos malignos metastáticos y/o localmente avanzados EGFR+. Open-label, multicenter, dose-escalation Phase I/II study to evaluate safety, pharmacokinetics and activity of RO5083945, a Glycoengineered Antibody against EGFR, in patients with metastatic and/or locally advanced malignant EGFR+ Solid Tumors
- Conditions
- Parte I: Tumores sólidos malignos metastáticos y/o localmente avanzados que expresan el receptor del factor de crecimiento endotelial (EGFR) Parte II: Cáncer colorrectal metastático o localmente avanzado con expresión de EGFR y del homólogo del oncogén viral del sarcoma 2 de rata Kirsten (KRAS) mutantePart I: Metastatic and/or locally advanced malignant solid tumors expressing (EGFR) Part II: Metastatic or locally advanced colorectal cancer expressing (EGFR) and mutant (KRAS)MedDRA version: 9.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerMedDRA version: 9.1Level: LLTClassification code 10049516Term: Malignant tumor
- Registration Number
- EUCTR2007-005939-28-ES
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 80
Patients in both Parts I and II of the study must meet the following criteria to be eligible for study entry:
1. Signed informed consent
2. Age = 18 years
3. ECOG Performance Status (PS) 0-1
4. Able and willing to comply with protocol requirements
5. Centrally confirmed EGFR expression in tumor tissue: >10%
of tumor cells show membrane staining of any intensity
6. Evidence of radiologically measurable or clinically evaluable disease
7. Last dose of systemic anti-neoplastic therapy or radiotherapy = 28 days prior to first RO5083945 infusion
8. All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved to Grade = 1, except alopecia and Grade 2 peripheral
neuropathy
9. Neutrophil count of = 1.5 x 10 exp9 cells/L, platelet count of = 75 x 10 exp9/L, Hb = 8 g/dL
10. Total bilirubin within normal limits (excluding Gilbert Syndrome)
11. AST and/or ALT = 2.5× ULN
12. Serum creatinine = 1.5 ULN
13. Female patients of childbearing potential must commit to using a reliable and appropriate methods of contraception until at least two months after the end of study treatment. A serum pregnancy test should be performed within 7 days
prior to the first dose of study treatment. Male patients with a partner of childbearing potential must agree to use a barrier contraception (condom) in addition to having their partner use another contraceptive method during the trial and for two months after the last dose. Reliable and appropriate methods of contraception include hormonal implants, oral contraceptives, intra-uterine devices or a barrier method used in conjunction with spermicidal jelly.
Patients in Part I of the study must also meet the following criteria to
be eligible for study entry:
14. Histologically or cytologically confirmed advanced stage, primary or metastatic EGFR+ solid tumors
15. No standard therapy exists Patients in Part II of the study must also meet the following criteria to be eligible for study entry:
16. Histologically or cytologically confirmed advanced stage, primary or metastatic EGFR+ and mutant KRAS colorectal cancer
17. Not more than 2 previous cytotoxic regimens for metastatic disease
18. Evidence of radiologically measurable and documented progressive disease
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients in Parts I and II who meet any of the following criteria will be
excluded from the study:
1. Concurrent therapy with any other investigational drug
2. History of NCI CTCAE Grade 3-4 toxicity resulting from previous anti-EGFR treatment (Grade 4 for skin toxicity)
3. Grade 3-4 peripheral neuropathy toxicity
4. Pregnant or lactating women
5. Known or suspected CNS metastases including leptomeningeal metastases
6. Poorly controlled hypertension (systolic >180 mm Hg or diastolic > 100 mm Hg)
7. Severe uncontrolled illness including poorly controlled diabetes mellitus, active or uncontrolled infection
8. Known infection with HBV, HCV and HIV
9. 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
10. Dementia or altered mental status that would prohibit informed consent
11. Major surgery or significant traumatic injury < 28 days prior to the 1st RO5083945 infusion (excluding biopsies)
Patients in Part II who also meet the following exclusion criteria will be excluded from the study:
12. wild type KRAS colorectal cancer
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method