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.

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2008-005074-12-ES
• Date of registration: 18/11/2008
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 04/03/2009
• Target sample size: 108
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-005074-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion criteria:
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

Exclusion criteria:
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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Part 1: Advanced, treatment-refractory solid tumors Part 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: 9.1 Level: LLT Classification code 10061451 Term: Colorectal cancer
MedDRA version: 9.1 Level: LLT Classification code 10033604 Term: Pancreatic cancer
MedDRA version: 9.1 Level: LLT Classification code 10033128 Term: Ovarian cancer

Intervention(s)

Product Name: AMG 655
Product Code: AMG 655
Pharmaceutical Form: Intravenous infusion
Current Sponsor code: AMG 655
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Product Name: AMG 479
Product Code: AMG 479
Pharmaceutical Form: Intravenous infusion
Current Sponsor code: AMG 479
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Main Objective: Part 1: To identify a dose of AMG 655 in combination with AMG 479 that is safe and
tolerated as determined by the incidence of dose limiting toxicity (DLT).
Part 2: To estimate the efficacy, as measured by the objective response rate (ORR;
confirmed complete response [CR] and partial response [PR] using modified Response Evaluation Criteria in Solid Tumors [RECIST]) of AMG 655 in combination with AMG 479.

Secondary Objective: Part 1:
- To evaluate the safety and tolerability of AMG 655 in combination with AMG 479.
- To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation.
- To evaluate the pharmacokinetics (PK) of AMG 655 and of AMG 479.
Part 2:
- To estimate the efficacy of AMG 655 in combination with AMG 479, as measured by
time to response, duration of response, and progression-free survival (PFS).
- To evaluate the safety and tolerability of AMG 655 in combination with AMG 479.
- To evaluate anti-AMG 655 antibody formation and anti-AMG 479 antibody formation.
- To evaluate the PK of AMG 655 and of AMG 479.

Primary end point(s): Part 1: The incidence of adverse events and clinical laboratory abnormalities defined as DLT
Part 2: ORR (confirmed CR and PR, by modified RECIST)

Secondary ID(s)

20070411

Ethics review

Status: Approved
Approval date: 22/12/2008
Contact:

Results

• Results available: Yes
• Date Posted: 17/10/2016
• Date Completed: 10/08/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-005074-12/results