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Center for Global Research Data

Predictors of therapeutic and adverse effects of medicines used in the treatment of gastrointestinal cancers

Lead Investigator: Ashley Hopkins, Flinders University
Title of Proposal Research: Predictors of therapeutic and adverse effects of medicines used in the treatment of gastrointestinal cancers
Vivli Data Request: 5290
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

There are many important medicines used in the treatment of gastrointestinal cancers. However, response and toxicity to many therapies is highly unpredictable. For example, many eligible patients do not respond to Anti–vascular endothelial growth factor (anti-VEGF) targeted therapy when used in the treatment of advanced gastrointestinal cancers. Thus, more research is required to confirm and explore novel predictive markers of therapeutic and adverse effects of medicines used in the treatment of gastrointestinal cancers.

This project seeks to enable improved prediction of the therapeutic and adverse outcomes of patients using medicines in the treatment of gastrointestinal cancers. Being able to identify the expected response and adverse effect profile may enable patients and clinicians to make better decisions regarding whether to commence, continue, discontinue or change dosing of these medicines.

Available data from various gastrointestinal cancers patients treated with relevant contemporary treatment options will be analysed to identify and validate predictors of the most important adverse effects, and clinical/biological/patient predictors of therapeutic outcomes such as response, tumor shrinkage, PFS and survival.

Study design:
A pooled observational cohort design will be used to conduct a meta-analysis of transparently shared clinical trials data.

Population:
Gastrointestinal cancers patients treated with contemporary treatment options.

Rationale for Study Selection and Selection of Populations/Participants:
To precisely and validly determine the relationship between potential predictors and outcomes of interest it is important to have the maximum sample size possible across a range of different study populations (an increased number of studies increases the population diversity, and is thus more comparable to standard clinical practice). Therefore, all studies collecting baseline and follow-up clinical characteristic data, as well as adverse event or therapeutic outcome data for patients with gastrointestinal cancers (gastric, colorectal, liver and pancreatic cancers) have been selected (model building will use the per-protocol populations).

How the data you have requested will help you answer the hypothesis:
Potential predictors of the adverse event or therapeutic outcomes will be screened according to biological and clinical plausibility and empirical evidence based on prior research. While exploratory univariable analyses will be conducted, a major focus will be on the development of optimal predictive performance multivariable models that can be developed into clinical prediction tools. As most of the data commonly collected within a clinical trial contains some information on the immune system, disease severity and prognosis, toxicity risk or drug exposure, it is important to have access to all the baseline and follow-up clinical/biological/patient characteristic data collected on an individual for any given study.

Requested Studies:

A Randomized, Double-blind, Multicenter Phase 3 Study of Irinotecan, Folinic Acid, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab or Placebo in Patients With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine
Sponsor: Eli Lilly and Company
Study ID: NCT01183780
Sponsor ID: 13856

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Capecitabine and Cisplatin With or Without Ramucirumab as First-line Therapy in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (RAINFALL)
Sponsor: Eli Lilly and Company
Study ID: NCT02314117
Sponsor ID: 15372

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study of Weekly Paclitaxel With or Without Ramucirumab (IMC-1121B) Drug Product in Patients With Metastatic Gastric Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine
Sponsor: Eli Lilly and Company
Study ID: NCT01170663
Sponsor ID: 13894

A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy
Sponsor: Eli Lilly and Company
Study ID: NCT00917384
Sponsor ID: 13893

A Randomized, Open-label Study of the Effect of First-line Herceptin in Combination With a Fluoropyrimidine and Cisplatin Versus Chemotherapy Alone on Overall Survival in Patients With HER2-positive Advanced Gastric Cancer
Sponsor: Roche
Study ID: NCT01041404
Sponsor ID: BO18255

A Double-blind, Randomised, Multicenter, Phase III Study of Bevacizumab in Combination With Capecitabine and Cisplatin Versus Placebo in Combination With Capecitabine and Cisplatin, as First-line Therapy in Patients With Advanced Gastric Cancer
Sponsor: Roche
Study ID: NCT00548548
Sponsor ID: AVF4200g

A Randomized, Open-label, Dose-escalation to Rash Study to Assess the Effect of Tarceva in Combination With Gemcitabine on Overall Survival in Patients With Metastatic Pancreatic Cancer.
Sponsor: Roche
Study ID: NCT00652366
Sponsor ID: BO21128

A Randomized, Open-label Phase III Intergroup Study: Effect of Adding Bevacizumab to Cross Over Fluoropyrimidine Based Chemotherapy (CTx) in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line Standard CTx/Bevacizumab Combination
Sponsor: Roche
Study ID: NCT00700102
Sponsor ID: ML18147

A Randomized, Three Arm Multinational Phase III Study to Investigate Bevacizumab (q3w or q2w) in Combination With Either Intermittent Capecitabine Plus Oxaliplatin (XELOX) (q3w) or Fluorouracil/Leucovorin With Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 Regimen Alone as Adjuvant Chemotherapy in Colon Carcinoma: The AVANT Study
Sponsor: Roche
Study ID: NCT00112918
Sponsor ID: CDR0000427299

A Randomized, Multicenter, Adaptive Phase II/III Study To Evaluate The Efficacy And Safety Of Trastuzumab Emtansine (T-DM1) Versus Taxane (Docetaxel Or Paclitaxel) In Patients With Previously Treated Locally Advanced Or Metastatic HER2-Positive Gastric Cancer, Including Adenocarcinoma Of The Gastroesophageal Junction
Sponsor: Roche
Study ID: NCT01641939
Sponsor ID: BO27952

A Randomized, Double-blind Study of the Effect of Avastin Plus Gemcitabine and Erlotinib Compared With Placebo Plus Gemcitabine and Erlotinib on Overall Survival in Patients With Metastatic Pancreatic Cancer
Sponsor: Roche
Study ID: NCT01214720
Sponsor ID: BO17706

An Open-Label Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) (“XELOX”) Versus Fluorouracil/Leucovorin as Adjuvant Therapy for Patients Who Have Undergone Surgery for Colon Carcinoma, AJCC/UICC Stage III (Dukes Stage C)
Sponsor: Roche
Study ID: NCT00069121
Sponsor ID: NO16968

An Open-Label Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) (“XELOX”) Versus Bolus and Continuous Infusion Fluorouracil/ Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) (“FOLFOX4”) as Treatment for Patients With Metastatic Colorectal Cancer Who Have Received Prior Treatment With CPT-11 in Combination With 5-FU/LV as First Line Therapy
Sponsor: Roche
Study ID: NCT00069108
Sponsor ID: NO16967

A 2×2 Factorial Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) (“XELOX”) With/Without Intravenous Bevacizumab (Q3W) Versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) (“FOLFOX-4”) With/Without Intravenous Bevacizumab (Q2W) as First-line Treatment for Patients With Metastatic Colorectal Cancer
Sponsor: Roche
Study ID: NCT00069095
Sponsor ID: NO16966

A Double-Blind, Randomized, Multicenter, Phase III Study of Bevacizumab in Combination With Capecitabine and Cisplatin Versus Placebo in Combination With Capecitabine and Cisplatin, as First-Line Therapy in Patients With Advanced Gastric Cancer.
Sponsor: Roche
Study ID: NCT00887822
Sponsor ID: ML22367

An Observational Study of Avastin (Bevacizumab) in Combination With Chemotherapy for Treatment of Metastatic or Locally Advanced and Unresectable Colorectal Cancer and Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Excluding Predominant Squamous Cell Histology)
Sponsor: Roche
Study ID: NCT00388206
Sponsor ID: AVF3991n

A Phase II, Multicenter, Double-Blind, Randomized, Active-Controlled Clinical Trial to Evaluate the Efficacy and Safety of rhuMAb VEGF (Bevacizumab), a Recombinant Humanized Monoclonal Antibody to Vascular Endothelial Growth Factor, in Combination With 5-Fluorouracil and Leucovorin Chemotherapy in Subjects With Metastatic Colorectal Cancer Who Are Not Optimal Candidates for First Line CPT-11
Sponsor: Roche
Study ID: NCT00109226
Sponsor ID: AVF2192g

A Phase III, Multicenter, Randomized, Active-Controlled Clinical Trial to Evaluate the Efficacy and Safety of rhuMAb VEGF (Bevacizumab) in Combination With Standard Chemotherapy in Subjects With Metastatic Colorectal Cancer
Sponsor: Roche
Study ID: NCT00109070
Sponsor ID: AVF2107g

A single arm study to assess the efficacy and safety of bevacizumab in combination with irinotecan and infusional 5-fluorouracil/folic acid regimens as first line treatment for patients with metastatic colorectal cancer.
Sponsor: Roche
Sponsor ID: MO18458

A Multicenter, Open Label, Phase I /Randomised Phase II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Oral Sorafenib for Advanced Hepatocellular Carcinoma Patients.
Sponsor: Boehringer Ingelheim
Study ID: NCT01004003
Sponsor ID: 1199.37

A Multicenter, Open Label, Phase I/Randomized II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Sorafenib for Advanced Hepatocellular Carcinoma Patients in Asia.
Sponsor: Boehringer Ingelheim
Study ID: NCT00987935
Sponsor ID: 1199.39

A Randomized, Multi-Center, Blinded, Placebo-Controlled Study Of Mapatumumab ([HGS1012], A Fully Monoclonal Antibody To TRAIL-R1) In Combination With Sorafenib As A First-Line Therapy In Subjects With Advanced Hepatocellular Carcinoma
Sponsor: GlaxoSmithKline
Study ID: NCT01258608
Sponsor ID: 200149

A Phase II Biomarker Identification Trial for Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Carcinoma
Sponsor: Roche
Study ID: NCT00674973
Sponsor ID: BO21129

A Double-blind, Randomised, Placebo Controlled Phase III Study of Nintedanib Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer Refractory to Standard Therapies.
Sponsor: Boehringer Ingelheim
Study ID: NCT02149108
Sponsor ID: 1199.52

Trial of rhuMAb VEGF Antibody Combined With 5 Fluourouracil and Leucovorin in Subjects With Locally Advanced or Metastatic Colorectal Cancer
Sponsor: Roche
Sponsor ID: AVF0780G