Clinical Trials /

Safety and Tolerability Study in Solid Tumors

NCT01803282

Description:

This is an open-label, multicenter, sequential dose-escalation, and expansion study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of andecaliximab (formerly GS-5745) alone and in combination with chemotherapy. The study consists of 2 parts (Parts A and B). Participants can only qualify for and participate in 1 part. Part A is a sequential dose escalation to determine the maximum tolerated dose of andecaliximab in participants with advanced solid tumors that are refractory to or intolerant to standard therapy or for which no standard therapy exists. In Part A, participants will receive andecaliximab only. Part A will consist of between 12 to 48 participants. Part B is a dose expansion to obtain additional safety and tolerability data for andecaliximab in participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, esophagogastric adenocarcinoma, colorectal cancer, or breast cancer. In Part B, participants will receive andecaliximab in combination with standard-of-care chemotherapy. Part B will consist of between 115 to 295 participants. Please note the study is currently only recruiting in the breast cancer cohorts.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Carcinoma
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01803282

Trial Eligibility

Document

Title

  • Brief Title: Safety and Tolerability Study in Solid Tumors
  • Official Title: A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GS-US-296-0101
  • NCT ID: NCT01803282

Conditions

  • Tumors
  • Pancreatic Cancer
  • Non-small Cell Lung Cancer
  • Esophagogastric Cancer
  • Colorectal Cancer
  • Breast Cancer

Interventions

DrugSynonymsArms
AndecaliximabGS-5745Andecaliximab
GemcitabineAndecaliximab with chemotherapy
Nab-paclitaxelAndecaliximab with chemotherapy
CarboplatinAndecaliximab with chemotherapy
PemetrexedAndecaliximab with chemotherapy
LeucovorinAndecaliximab with chemotherapy
OxaliplatinAndecaliximab with chemotherapy
5-FUAndecaliximab with chemotherapy
BevacizumabAndecaliximab with chemotherapy
IrinotecanAndecaliximab with chemotherapy
PaclitaxelAndecaliximab with chemotherapy

Purpose

This is an open-label, multicenter, sequential dose-escalation, and expansion study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of andecaliximab (formerly GS-5745) alone and in combination with chemotherapy. The study consists of 2 parts (Parts A and B). Participants can only qualify for and participate in 1 part. Part A is a sequential dose escalation to determine the maximum tolerated dose of andecaliximab in participants with advanced solid tumors that are refractory to or intolerant to standard therapy or for which no standard therapy exists. In Part A, participants will receive andecaliximab only. Part A will consist of between 12 to 48 participants. Part B is a dose expansion to obtain additional safety and tolerability data for andecaliximab in participants with advanced pancreatic adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, esophagogastric adenocarcinoma, colorectal cancer, or breast cancer. In Part B, participants will receive andecaliximab in combination with standard-of-care chemotherapy. Part B will consist of between 115 to 295 participants. Please note the study is currently only recruiting in the breast cancer cohorts.

Trial Arms

NameTypeDescriptionInterventions
AndecaliximabExperimentalParticipants will receive andecaliximab by intravenous (IV) infusion over approximately 30 minutes every 2 weeks on Days 1 and 15 of each 28-day treatment cycle or every 3 weeks on Day 1 of each 21-day treatment cycle (NSCLC group only).
  • Andecaliximab
Andecaliximab with chemotherapyExperimentalParticipants will receive andecaliximab by IV infusion every 2-3 weeks in combination with chemotherapy as follows: Pancreatic adenocarcinoma, esophagogastric adenocarcinoma, CRC, and breast cancer: Administered intravenously on Days 1 and 15 of each 28-day treatment cycle Non Small Cell Lung Carcinoma (NSCLC): Administered intravenously on Day 1 of each 21-day treatment cycle In Part B, andecaliximab will be given in combination with one of the following chemotherapy regimens: Pancreatic adenocarcinoma: gemcitabine and nab-paclitaxel NSCLC: lung adenocarcinoma: carboplatin and pemetrexed lung squamous cell carcinoma: carboplatin and paclitaxel Esophagogastric adenocarcinoma: mFOLFOX6 (leucovorin+oxaliplatin+5-FU) First-line colorectal cancer (CRC): mFOLFOX6 and bevacizumab Second-line colorectal cancer: FOLFIRI (leucovorin+irinotecan+5-FU) and bevacizumab Breast cancer: Paclitaxel
  • Andecaliximab
  • Gemcitabine
  • Nab-paclitaxel
  • Carboplatin
  • Pemetrexed
  • Leucovorin
  • Oxaliplatin
  • 5-FU
  • Bevacizumab
  • Irinotecan
  • Paclitaxel

Eligibility Criteria

        Key Inclusion Criteria:

          -  Part A: histologically or cytologically confirmed advanced malignant solid tumor that
             is refractory to or intolerant of standard therapy or for which no standard therapy is
             available

          -  Part B: Pancreatic Adenocarcinoma

               -  Presence of histologically confirmed inoperable locally advanced or metastatic
                  pancreatic adenocarcinoma

          -  Part B: NSCLC

               -  Stage IIIB with malignant pleural effusion/pleural seeding or stage IV
                  histologically confirmed NSCLC

               -  Absence of known epidermal growth factor receptor (EGFR) mutation

               -  Absence of known translocation or inversion events involving the ALK gene locus
                  (resulting in EML4-ALK fusion)

          -  Part B: Esophagogastric Adenocarcinoma:

               -  Histologically confirmed inoperable advanced gastric adenocarcinoma (including
                  adenocarcinoma of the gastrooesophageal junction) or relapsed gastric
                  adenocarcinoma

               -  Human epidermal growth factor receptor 2 (HER2)-negative tumor (primary tumor or
                  metastatic lesion)

          -  Part B: First-Line Colorectal Cancer

               -  Histologically confirmed inoperable advanced adenocarcinoma of the colon or
                  rectum

               -  Radiographically measureable disease

               -  No prior cytotoxic chemotherapy to treat their metastatic disease

          -  Part B: Second-Line Colorectal Cancer

               -  Histologically confirmed inoperable advanced adenocarcinoma of the colon or
                  rectum

               -  Radiographically measureable disease

               -  Received first-line combination therapy containing oxaliplatin and
                  fluoropyrimidine with or without bevacizumab for metastatic disease with
                  documented evidence of disease progression during or after treatment completion

          -  Part B: Breast Cancer

               -  Histologically or cytologically confirmed metastatic breast cancer

               -  Radiographically measureable disease

               -  Previous hormonal therapy for metastatic breast cancer or cytotoxic adjuvant
                  chemotherapy is allowed

               -  Treatment with weekly single-agent paclitaxel is appropriate in the opinion of
                  the treating physician

               -  HER-2 negative tumor (primary tumor or metastatic lesion)

          -  Adequate organ function

        Key Exclusion Criteria:

          -  Pregnant or lactating

          -  Individuals with known central nervous system (CNS) metastases, unless metastases are
             treated and stable and the individual does not require systemic steroids

          -  Myocardial infarction, symptomatic congestive heart failure, unstable angina, or
             serious uncontrolled cardiac arrhythmia within the last 6 months

          -  Anti-tumor therapy within 28 days of study drug dosing; concurrent use of hormone
             therapy for breast or prostate cancer is permitted

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as evaluated by incidence of AEs, assessment of clinical laboratory test findings, physical examination, 12-lead ECG, and vital signs measurements
Time Frame:Baseline to completion of follow up evaluation. If follow up evaluation is not completed, baseline to date of first documented progression or date of death from any cause, whichever came first
Safety Issue:
Description:AEs that begin on or after the first study drug administration and within 30 days after last study drug administration will be summarized by dose level (Part A) and tumor type (Part B).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Trial Keywords

  • Solid Tumor
  • NSCLC
  • Pancreatic
  • Esophagogastric
  • Colorectal
  • Breast

Last Updated

August 24, 2017