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

Phase 1

• Conditions: Part I: Metastatic and/or locally advanced malignant solid tumors expressing Epidermal Growth Factor Receptor (EGFR) Part II: Metastatic or locally advanced colorectal cancer expressing EGFR and mutant Kirsten rat sarcoma 2 viral oncogene homolog (KRAS); MedDRA version: 9.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer; MedDRA version: 9.1Level: LLTClassification code 10049516Term: Malignant tumor

• Registration Number: EUCTR2007-005939-28-FR
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-10-21
• Study Completion: 2011-06-21
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Patients in both Part 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: =1% 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. Palliative radiotherapy for bone pain relief is
allowed at any time before the 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 109 cells/L, platelet count of? = 75 x 109/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

Exclusion Criteria

The presence of any of the following criteria in both Part I and II will exclude a patient
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