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Phase 1/1b Study of Rilotumumab in Japanese Subjects With Advanced Solid Tumors or Advanced or Metastatic Gastric or GEJ

Primary Purpose

Part 1- Advanced Solid Tumors, Part 2- Advanced or Metastatic Gastric Cancer, Part 2- Advanced or Metastatic GEJ

Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Rilotumumab
Rilotumumab
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Part 1- Advanced Solid Tumors focused on measuring Advanced Solid Tumors, Advanced or Metastatic Gastric Cancer, Advanced or Metastatic GEJ, Gastric Cancer

Eligibility Criteria

20 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Rilotumumab Monotherapy

Rilotumumab plus CX

Arm Description

Cohort 1A: Rilotumumab 10 mg/kg IV Q2W Cohort 1B: Rilotumumab 20 mg/kg IV Q2W Cohort 1C (if needed): Rilotumumab 15 mg/kg IV Q2W

Cohort 2A: Rilotumumab 15 mg/kg IV Day 1 Q3W Cisplatin 80 mg/m2 IV (max of 6 cycles) Day 1 Q3W Capecitabine 1000 mg/m2 PO BID, Days 2-14 Q3W Cohort 2B (if needed): Rilotumumab 10 mg/kg IV Day 1 Q3W Cisplatin 80 mg/m2 IV (max of 6 cycles) Day 1 Q3W Capecitabine 1000 mg/m2 PO BID, Days 2-14 Q3W

Outcomes

Primary Outcome Measures

Part1: Dose-limiting toxicities (DLT) for each dose level of rilotumumab tested
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
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 Outcome Measures

Part 1: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies.
AEs and laboratory abnormalities are reported by CTCAE (version 3.0) criteria
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.
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.
Part 2: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies not defined as DLTs.
AEs and laboratory abnormalities are reported by CTCAE (version 3.0) criteria
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.
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.

Full Information

First Posted
January 4, 2013
Last Updated
February 26, 2016
Sponsor
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT01791374
Brief Title
Phase 1/1b Study of Rilotumumab in Japanese Subjects With Advanced Solid Tumors or Advanced or Metastatic Gastric or GEJ
Official Title
A Multicenter, Phase 1/1b, Open Label Study Evaluating the Safety, Tolerability and Pharmacokinetics of Rilotumumab in Japanese Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Part 1- Advanced Solid Tumors, Part 2- Advanced or Metastatic Gastric Cancer, Part 2- Advanced or Metastatic GEJ
Keywords
Advanced Solid Tumors, Advanced or Metastatic Gastric Cancer, Advanced or Metastatic GEJ, Gastric Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rilotumumab Monotherapy
Arm Type
Experimental
Arm Description
Cohort 1A: Rilotumumab 10 mg/kg IV Q2W Cohort 1B: Rilotumumab 20 mg/kg IV Q2W Cohort 1C (if needed): Rilotumumab 15 mg/kg IV Q2W
Arm Title
Rilotumumab plus CX
Arm Type
Experimental
Arm Description
Cohort 2A: Rilotumumab 15 mg/kg IV Day 1 Q3W Cisplatin 80 mg/m2 IV (max of 6 cycles) Day 1 Q3W Capecitabine 1000 mg/m2 PO BID, Days 2-14 Q3W Cohort 2B (if needed): Rilotumumab 10 mg/kg IV Day 1 Q3W Cisplatin 80 mg/m2 IV (max of 6 cycles) Day 1 Q3W Capecitabine 1000 mg/m2 PO BID, Days 2-14 Q3W
Intervention Type
Drug
Intervention Name(s)
Rilotumumab
Other Intervention Name(s)
AMG 102
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rilotumumab
Other Intervention Name(s)
AMG 102
Intervention Description
Drug: Rilotumumab 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. Drug: Cisplatin A platinum containing chemo-therapy compound that reacts in vivo, binding to and causing crosslinking of DNA, which ultimately triggers apoptosis (programmed cell death). Drug: Capecitabine A chemo-therapy prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.
Primary Outcome Measure Information:
Title
Part1: Dose-limiting toxicities (DLT) for each dose level of rilotumumab tested
Description
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.
Time Frame
28 days
Title
Part 2: Dose-limiting toxicities (DLT) for each dose level of rilotumumab in combination with cisplatin and capecitabine (CX) chemotherapy tested
Description
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.
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Part 1: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies.
Description
AEs and laboratory abnormalities are reported by CTCAE (version 3.0) criteria
Time Frame
4 months average
Title
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.
Time Frame
4 months average
Title
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.
Time Frame
4 months average
Title
Part 2: Incidence of AEs, clinical laboratory abnormalities and anti-rilotumumab antibodies not defined as DLTs.
Description
AEs and laboratory abnormalities are reported by CTCAE (version 3.0) criteria
Time Frame
7 months average
Title
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.
Time Frame
7 months average
Title
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.
Time Frame
7 months average

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Nagoya-shi
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Research Site
City
Kashiwa-shi
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
Research Site
City
Matsuyama-shi
State/Province
Ehime
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Research Site
City
Sapporo-shi
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Research Site
City
Kawasaki-shi
State/Province
Kanagawa
ZIP/Postal Code
216-8511
Country
Japan
Facility Name
Research Site
City
Kitaadachi-gun
State/Province
Saitama
ZIP/Postal Code
362-0806
Country
Japan
Facility Name
Research Site
City
Suntou-gun
State/Province
Shizuoka
ZIP/Postal Code
411-8777
Country
Japan

12. IPD Sharing Statement

Citations:
PubMed Identifier
28973403
Citation
Doi T, Yamaguchi K, Komatsu Y, Muro K, Nishina T, Nakajima TE, Tang R, Yang H, Zhang Y, Jung AS, Ang A, Yasui H. A Phase 1/1b tolerability study of rilotumumab alone or in combination with cisplatin and capecitabine in Japanese patients with gastric cancer. Jpn J Clin Oncol. 2017 Nov 1;47(11):1002-1009. doi: 10.1093/jjco/hyx114.
Results Reference
derived
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website

Learn more about this trial

Phase 1/1b Study of Rilotumumab in Japanese Subjects With Advanced Solid Tumors or Advanced or Metastatic Gastric or GEJ

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