A Phase 1b/2 Open Label, Dose Escalation Study of AMG 655 in Combination with AMG 479 in Subjects with Advanced, Refractory Solid Tumors.--------------------------------------------------------Estudio abierto de fase 1b/2 con escalada de dosis de AMG 655 en combinación con AMG 479 en sujetos con tumores sólidos refractarios y avanzados.
- Conditions
- Part 1: Advanced, treatment-refractory solid tumorsPart 2: Advanced non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic cancer, ovarian cancer, or sarcoma.------------------------------------------------------------Parte 1:tumores sólidos refractarios y avanzados.Parte 2:Cáncer de pulmón no microcítico avanzado (CPNM), cáncer colorrectal (CRC), cáncer pancreático, cáncer de ovario o sarcoma.MedDRA version: 9.1Level: LLTClassification code 10061451Term: Colorectal cancerMedDRA version: 9.1Level: LLTClassification code 10033604Term: Pancreatic cancerMedDRA version: 9.1Level: LLTClassification code 10033128Term: Ovarian cancer
- Registration Number
- EUCTR2008-005074-12-ES
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 108
Disease Related
- Part 1: Histologically or cytologically confirmed, locally advanced or metastatic,
treatment-refractory solid tumors
- Part 2: Histologically or cytologically confirmed, locally advanced or metastatic
- NSCLC (squamous or non-squamous cell carcinoma; up to 2 prior treatment regimens)
- CRC (up to 2 prior treatment regimens)
- Pancreatic cancer (up to 1 prior treatment regimen)
- Ovarian cancer (up to 2 prior treatment regimens), or
- Sarcoma (up to 2 prior treatment regimens)
- according to cohort availability
- Part 2: Measurable disease according to modified RECIST (at least 1 measurable
lesion)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix G)
- Life expectancy ≥ 3 months
Demographic.
- Women or men ≥ 16 years of age
Ethical
- Before any study-specific procedure, the appropriate written informed consent must
be obtained (Section 12.1)
Laboratory
Within 7 days before enrollment, the following test results must be obtained:
- Hematological function, as follows:
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
(without transfusion ≤ 14 days prior to enrollment)
- Renal function, as follows:
- Serum creatinine ≤ 2 x ULN
- Hepatic function, as follows:
- Aspartate aminotransferase (AST; SGOT) ≤ 2.5 x ULN
( 5 x ULN if attributable to liver metastases)
- Alanine aminotransferase (ALT; SGPT) ≤ 2.5 x ULN
(≤ 5 x ULN if attributable to liver metastases)
- Total Bilirubin ≤ 1.5 x ULN
(≤ 3 x ULN for subjects with UGT1A1 promoter polymorphism ie, Gilbert syndrome, confirmed by genotyping or Invader UGT1A1 molecular assay prior to enrollment)
- Coagulation:
- Partial thromboplastin time (PTT) ≤ 1.3 x ULN
- International normalized ratio (INR) ≤ 1.5,
- Amylase ≤ 2 x ULN
- Lipase ≤ 2 x ULN
- Adequate glycemic function, for subjects with known diabetes (Type 1 or 2), as
follows:
- Must be controlled with a glycosylated hemoglobin (HgbA1c) of ≤ 8.0%
- Documented fasting blood sugars ≤ 160 mg/dL. Diabetic subjects who have
recently had their glycemic control regimens adjusted and have documented fasting blood glucose concentrations ≤ 160 mg/dL may be considered regardless of HgbA1c value, if per investigator discretion they are considered to have adequate glycemic function
- Negative pregnancy test within 3 days prior to enrollment (females of child-bearing potential only)
General
- Plan to begin protocol specific therapy ≤ 7 days after enrollment
Are the trial subjects under 18? yes
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
Disease Related
- Presence of uncontrolled central nervous system (CNS) disease:
- Subjects with CNS metastases that are both definitively treated and
stably controlled are eligible if all of the following apply:
(1) definitive therapy has been administered (surgery and/or radiation therapy);
(2) there is no additional treatment planned for brain metastases;
(3) the subject is clinically stable; and
(4) the subject is off corticosteroids or on a stable dose of corticosteroids for at
least 14 days prior to enrollment.
- Part 2: Any prior or synchronous other malignancy, except:
- Malignancy treated with curative intent and with no known active disease present
for ≥ 3 years before enrollment and considered to be at low risk for recurrence by
the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
Cancer Therapy
- Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or
approved anticancer proteins/antibodies therapy ≤ 28 days before enrollment,
except:
- In Part 1, patients may continue approved hormonal therapy as medically
indicated
- Unresolved toxicity(ies) from prior anti-cancer therapy, which may increase the risks
associated with study participation
- Prior treatment with death receptor agonists (including but not limited to
rhApo2L/TRAIL [AMG 951], apomab, mapatumumab, lexatumumab, CS-1008)
- Prior treatment with IGF receptor antagonists (including but not limited to
CP-751,871, MK0646, AVE1642 or IMC-A12)
- Patients may not have received prior radiotherapy to > 25% of the bone marrow.
Radiation must have been concluded ≥ 14 days prior to enrollment. Patients must
have recovered from all potential side effects and must be clinically stable.
Medications/ Treatments
- Therapeutic anticoagulation treatment within 7 days prior to enrollment.
- Prophylactic anticoagulation of venous access devices (eg, with low-dose
coumadin [1-2 mg/day] or low-dose heparin) is allowed, provided PTT and INR
eligibility criteria are met.
- Recent infection requiring systemic anti-infective treatment that was completed
- 14 days before enrollment (with the exception of uncomplicated urinary tract
infection or upper respiratory tract infection)
Medical Conditions
- Major surgical procedure ≤ 28 days before enrollment, or not yet recovered from
prior major surgery
- Minor surgical procedure (eg, open biopsy) ≤ 7 days before enrollment, or not yet
recovered from prior minor surgery.
Note: uncomplicated placement of vascular access device, fine needle aspiration,
thoracocentesis or paracentesis ≥ 3 days prior to enrollment is acceptable
- History of bleeding diathesis
- Pulmonary embolism or arterial/venous thromboembolism within 6 months
- Known positive test for human immunodeficiency virus, hepatitis C virus or acute or
chronic hepatitis B infection
- Any clinically significant medical or psychiatric condition, co-morbid disease,
addictive disorder, or laboratory abnormality (eg, cardiovascular disease or chronic
obstructive pulmonary disease), which may increase the risks associated with study
participation or study treatments or could interfere with the safe delivery of study
treatment or increase risk of toxicity
- Subject has any kind of disorder that compromises the ability of the subject to
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