Part 1- Advanced Solid Tumors, Part 2- Advanced or Metastatic Gastric Cancer, Part 2- Advanced or Metastatic GEJ
Conditions
Keywords
Advanced Solid Tumors, Advanced or Metastatic Gastric Cancer, Advanced or Metastatic GEJ, Gastric Cancer
Brief summary
This is an open label phase 1/1b study of Rilotumumab in Japanese subjects with advanced solid tumors or metastatic gastric esphagogastric (GEJ) adenocarcinoma.
Interventions
DRUGRilotumumab
Rilotumumab is a fully human monoclonal antibody immunoglobulin G, type 2 (IgG2) against human hepatocyte growth factor/scatter (HGF/SF) that blocks binding of HGF/SF to its receptor MET, inhibiting HGF/MET-driven activities in cells.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Japanese subjects with pathologically confirmed unresectable locally advanced or metastatic carcinoma which is refractory to standard therapies or for which there is no standard therapy (Part 1 only) * Japanese subjects with pathologically confirmed MET-positive (fulfilling the MET IHC criteria as defined by validated IVD \[in vitro diagnostic\]) unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma (Part 2 only) * Eastern Cooperative Oncology Group (ECOG) Performance Status (0 or 1) * Availability of archival tumor tissue (Part 2 only) * Evaluable (measurable or non-measurable) disease by RECIST 1.1 criteria * Able to tolerate infusions and take oral medications (Part 2 only) Key
Exclusion criteria
* Previous systemic therapy (including chemotherapy, biologic, immunotherapy, or investigational therapy) for locally advanced or metstatic gastric or GEJ adenocarcinoma (Part 2 only) * Less than 6 months have elapsed from completion of prior neoadjuvant or adjuvant chemotherapy or chemotherapy to enrollment (Part 2 only) * Squamos cell history (Part 2 only) * Known HER2-overexpressing unresectable locally advanced or metastatic gastric or GEJ adenocarcinoma (Part 2 only) * Resectable disease or suitable for definitive chemoradiation * Subjects who have persistent gastric outlet obstruction, complete dysphagia or are dependent upon jejunostomy for feeding (Part 2 only) * Known central nervous system metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part1: Dose-limiting toxicities (DLT) for each dose level of rilotumumab tested | 28 days | DLTs are defined as grade 3 or higher adverse events that are related to rilotumumab during the first cycle of therapy. This does not include specific toxicities (eg nausea and vomiting) that are common in cancer patients unless specific criteria are met. |
| Part 2: Dose-limiting toxicities (DLT) for each dose level of rilotumumab in combination with cisplatin and capecitabine (CX) chemotherapy tested | 21 days | DLTs are defined as grade 3 or higher adverse events that are related to rilotumumab or the combination of rilotumumab and CX during the first cycle of therapy. This does not include specific toxicities (eg nausea and vomiting) that are common in cancer patients unless specific criteria are met. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Pharmacokinetics parameters of rilotumumab monotherapy as measured by: Maximum concentration, time to achieve maximum concentration, observed minimum concentration, area under the concentration-time curve, terminal elimination half-life. | 4 months average | — |
| Part 1: Evaluate efficacy based on the treatment effects of rilotumumab monotherapy as measured by the following: Objective Response Rate, duration of response, progression-free survival. | 4 months average | — |
| Part 2: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies not defined as DLTs. | 7 months average | AEs and laboratory abnormalities are reported by CTCAE (version 3.0) criteria |
| Part 2: Evaluate efficacy based on the treatment effects of rilotumumab in combination with cisplatin and capecitabine as measured by the following: Objective Response Rate, duration of response, progression-free survival, overall survival. | 7 months average | — |
| Part 2: Pharmacokinetics parameters of rilotumumab in combination with cisplatin and capecitabine as measured by: Maximum concentration, observed minimum concentration, area under the concentration-time curve. | 7 months average | — |
| Part 1: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies. | 4 months average | AEs and laboratory abnormalities are reported by CTCAE (version 3.0) criteria |
Countries
Japan
Outcome results
None listed