E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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 give written informed consent and/or to comply with study procedures General - Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s) - Subject previously enrolled in this study - Subject of child-bearing potential is evidently pregnant (eg, positive human chorionic gonadotropin test) or is breast feeding - Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions ie, double barrier contraceptive methods (eg, diaphragm plus condom), or abstinence during the course of the study and for 3 months after the last study drug administration for women, and 6 months for men - Subject has known hypersensitivity to any of the products to be administered during the study - Subject is not able to tolerate IV drug infusions - Subject unwilling or unable to comply with study requirements - Subject will not be available for follow-up assessments |
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E.5 End points |
E.5.1 | 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) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the clinical study will be defined as the date when all subjects have completed the long-term follow-up period, have withdrawn from study or have died (until a maximum 36 months from the date the last subject was enrolled), whichever is earlier. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |