Colorectal Cancer
Conditions
Keywords
CRC, Colon cancer, Avastin, APM4187g
Brief summary
This is a Phase Ib, open-label, multicenter, dose-escalation study designed to assess if PRO95780 in combination with two different irinotecan-containing regimens is safe and tolerable in patients with metastatic colorectal cancer (mCRC) who have progressed following, or cannot tolerate, first-line therapy with 5-fluorouracil-, oxaliplatin-, and bevacizumab-containing regimens. This study will also make a preliminary assessment of the anti-tumor activity of PRO95780 in combination with irinotecan and cetuximab or the FOLFIRI regimen plus bevacizumab.
Interventions
DRUGbevacizumab
(Only for patients not previously treated with bevacizumab) Intravenous repeating dose
DRUGcetuximab
Intravenous repeating dose
DRUGFOLFIRI regimen
Intravenous repeating dose
DRUGirinotecan
Intravenous repeating dose
DRUGPRO95780
Intravenous repeating dose
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Age ≥ 18 years * Histologically confirmed CRC with evidence of metastases and measurable tumor lesions * Documented disease progression following, or intolerance to, treatment with 5-fluorouracil, oxaliplatin, and bevacizumab-based therapy * Life expectancy \> 3 months * For patients of reproductive potential (males and females), use of reliable means for contraception (e.g., contraceptive pill, intrauterine device \[IUD\], physical barrier) throughout the trial and for 6 months following their final exposure to study treatment * Willingness and capability to be accessible for study follow-up
Exclusion criteria
* Patients who have a Kras mutation will be excluded from receiving cetuximab-containing regimens * Prior radiotherapy to a measurable metastatic lesion(s) to be used for response assessment, unless the lesion has progressed subsequent to the radiotherapy * Recent radiotherapy to a peripheral lesion, thoracic, abdominal, or pelvic field * Recent chemotherapy, hormonal therapy, or immunotherapy * Evidence of clinically detectable ascites * Other invasive malignancies within 5 years * History or evidence of active central nervous system (CNS) disease * Current or recent participation in another experimental drug study * Clinically significant cardiovascular disease * Active infection requiring parenteral antibiotics * Recent major surgical procedure, open biopsy, significant traumatic injury, fine needle aspirations, or anticipation of need for major surgical procedure during the course of the study * Known or suspected to be positive for the human immunodeficiency virus (HIV) * Known to be positive for hepatitis C or hepatitis B surface antigen * History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or specified study treatment * Pregnancy (positive pregnancy test) or breast feeding * Serious, non-healing wound, ulcer, or bone fracture * Known sensitivity to any of the products administered during the study * Any disorder that compromises the ability of the patient to provide written informed consent and/or comply with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and nature of dose-limiting toxicities | Through study completion or early study discontinuation |
Secondary
| Measure | Time frame |
|---|---|
| Incidence, nature, and severity of adverse events | Through study completion or early study discontinuation |
| Change in vital signs | Through study completion or early study discontinuation |
| Incidence and severity of infusion reactions | Through study completion or early study discontinuation |
Outcome results
None listed