Phase 2, single arm study of ticilimumab in patients with refractory metastatic adenocarcinoma of the colon or rectum
- Conditions
- Refractory meatstatic adenocarcinoma of the colon or rectumMedDRA version: 8,0Level: VTcClassification code 10061289
- Registration Number
- EUCTR2006-001270-24-DE
- Lead Sponsor
- Pfizer Pharma GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1.Histologically or cytologically confirmed adenocarcinoma arising in the colon or rectum.
2.Radiographic evidence of metastatic, progressive disease following standard therapies. Patients in the United States will have been treated previously with, or have a significant known contraindication to, a fluorpyrimidine, irinotecan, oxaliplatin, bevacizumab (Avastin®), and cetuximab (Erbitux®). Patients outside of the United States will have been treated with, or have a contraindication to, whichever of these drugs are routinely used and available in standard practice in that country.
3.Evidence of measurable disease as per RECIST criteria
•Measurable Disease: Can be accurately measured in at least one dimension. Lesions on CT scan must have longest diameter = 2.0 cm using conventional techniques or = 1.0 cm with spiral CT scan.
4.Male or female, 18 years of age or older.
5.ECOG performance status 0-1.
6.Adequate bone marrow, hepatic and renal function determined within 14 days prior to initial dose of ticilimumab, defined as:
a.Absolute neutrophil count = 1.5 x 109cells/L.
b.Platelets = 100 x 109/L.
c.Hemoglobin = 9 g/dL.
d.Aspartate and alanine aminotransferases (AST, ALT) =2.5 x ULN (=5 x ULN if documented liver metastases are present).
e.Total serum bilirubin =2 x ULN (patients with Gilbert’s Syndrome: Direct serum bilirubin =2 x ULN)
f.Serum creatinine =2.0 mg/dL or calculated creatinine clearance = 60 mL/min.
7.Completion of prior chemotherapy, immunotherapy or radiation therapy at least 3 weeks before enrollment.
8.Recovered from all prior treatment-related toxicities to baseline status or to NCI CTCAE (v 3.0) Grade =1 except for toxicities not considered a safety risk such as alopecia or residual peripheral neuropathy resulting from prior systemic therapy.
9.Negative pregnancy test within 72 hours of initial dose of ticilimumab for female of childbearing potential. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
10.Females of childbearing potential who have not undergone surgical sterilization must agree to practice a form of effective contraception prior to entry into the study and for 12 months following the last dose of study drug. The definition of effective contraception will be based on the judgment of the treating investigator.
11.Must be willing and able to provide written informed consent.
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
1.Concomitant treatment with other anticancer therapy.
2.Previous treatment with other anti-CTLA4 agents (eg, MDX-010).
3.Known brain metastases or uncontrolled pleural effusions. Controlled will be defined as documented to be stable at least 4 weeks prior to enrollment.
4.History of chronic inflammatory or autoimmune disease (eg, Addison’s disease, multiple sclerosis, Graves disease, Hashimoto’s thyroiditis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.). Psoriasis that is current or active in the last 3 years. Active vitiligo or a history of vitiligo will not be a basis for exclusion.
5.Known active or chronic viral hepatitis.
6.History in the last 5 years of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding not associated with the disease under study, or current acute colitis of any origin.
7.Received an immunosuppressive dose of corticosteroids or other immunosuppressive medication (eg, methotrexate, rapamycin) within 4 weeks of enrollment. Note: Patients with adrenal insufficiency may take up to 5 mg of prednisone or equivalent daily. Topical and inhaled corticosteroids in standard doses are allowed. Steroids (eg, Decadron) to prevent or control nausea during prior cancer treatment are allowed.
8.Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
9.Any serious, uncontrolled medical disorder or uncontrolled active infection that would impair the ability to receive study treatment in the judgment of the treating investigator.
10.Diagnosis of any second malignancy within the last 3 years except basal cell carcinoma, squamous cell skin cancer, or carcinoma in situ of the cervix that has been adequately treated with no evidence of recurrent disease for 12 months.
11.Pregnancy or breast feeding.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the best overall response rate per RECIST (BRR) in patients with metastatic adenocarcinoma of the colon or rectum treated with ticilimumab;Primary end point(s): Best response per RECIST in patients treated with ticilimumab;Secondary Objective: •To assess additional evidence of anti-tumor activity as measured by duration of response, progression-free survival and overall survival<br>•To evaluate the safety and tolerability of ticilimumab in this population<br>•To obtain pharmacokinetic (PK) data to be evaluated in a future meta analysis of ticilimumab pharmacokinetics<br>•To identify any human anti human antibody (HAHA) response to ticilimumab<br>•To identify potential relationships between polymorphisms in the Cytotoxic T lymphocyte-associated antigen 4 (CTLA4), Fcgamma receptor IIa (FcgRIIa), IgG2a genes with safety and/or immune response of patients treated with ticilimumab<br>
- Secondary Outcome Measures
Name Time Method