Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Carcinoma

Adenocarcinoma

Carcinoma, Hepatocellular

Liver Diseases

Liver Neoplasms

Gastrointestinal Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Angiogenesis Inhibitors

Sorafenib

Enzyme Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Tablets, Oral, 17.5 mg, Once Daily, Until disease progression or unacceptable toxicity

ABT-869

Tablets, Oral, 400 mg, Twice Daily, Until disease progression or unacceptable toxicity.

Justin Ricker, MD

The primary objective of this study is to assess the overall survival (OS) of oral linifanib given as monotherapy once daily (QD) compared to sorafenib given twice daily (BID) per standard of care in subjects with advanced or metastatic HCC.

The IDMC recommended discontinuation of the study, and, the protocol was amended to end study treatment.

Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

An Open-label, Randomized Phase 3 Study of the Efficacy and Tolerability of Linifanib (ABT-869) Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma (HCC)

Abbott

Skin and Connective Tissue Diseases

Rare Diseases

Neoplasm Metastasis

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Tin Fluorides

Sunitinib

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

CGT9486 plus sunitinib

Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

CGT9486

Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

Participants will receive sunitinib orally until study stopping rules are met.

Cogent Biosciences

Jessica Sachs, MD

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner.

This is a multi-part study: Part 1a is a single-arm design, Part 1b is a two-arm parallel design drug-drug interaction evaluation in the first treatment cycle and single-arm design in subsequent treatment cycles, and Part 2 is a randomized two-arm parallel comparator study

(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors

Area under the plasma concentration-time curve (AUC)

Time to maximum observed plasma concentration (Tmax)

Time from first dose to documented disease progression or death due to any cause, whichever occurs first

Incidence and severity of Adverse Events from first dose of study drug

Incidence and severity of Serious Adverse Events from first dose of study drug

Incidence of Adverse Events leading to dose modifications from first dose of study drug

Change from baseline in laboratory results

Time from first dose to death due to any cause

Percentage of subjects who achieved documented complete response (CR) + confirmed partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks

Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1

Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first

Change in individual scores in patients with locally advanced, unresectable, or metastatic GIST treated with CGT9486 in combination with sunitinib compared with patients treated with sunitinib monotherapy. The scale comprises 30 questions, 24 of which are aggregated into 9 multi-item scales, to include 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and 1 global health status scale. The remaining 6 single-item scales assess symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.

Cogent Biosciences, Inc.

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Adenoma

Neuroendocrine Tumors

Neoplasms, Germ Cell and Embryonal

Endocrine Gland Neoplasms

Adenoma, Islet Cell

Pancreatic Diseases

Neoplasms, Nerve Tissue

Endocrine System Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Pancreatic Cancer

Neuroendocrine Tumor

Neuroepithelioma

sunitinib 37.5 mg/day (per os) for 6 months

Sutent

Eric Raymond, Professor

The purpose of this study is to identify predictive molecular markers of response to continuous daily sunitinib at dose of 37.5 mg used in patients with poorly-differentiated Advanced/Inoperable NEURO-Endocrine Tumors.

Hypothesis:

* To distinguish molecular markers based on their expression at the initial biopsy, their detection by proteomic analysis and demonstrating that tumor or vascular cells are straightaway sensitive to sunitinib (markers sensitivity).
* The presence of these markers at the initial biopsy predict the sensitivity to sunitinib(Positive predictive value of markers)

Neuroendocrine tumors (NET) are rare malignancies (1-2% of digestive cancers); and there is, in recent years, a slow but steady increase in their incidence. Despite the joint efforts of several research groups, which led to the new WHO classification (2002), the natural history of the disease remains heterogene and the resistance to conventional cytotoxic treatment remains the common denominator of these tumors.

Indeed, the prognosis of patients with metastatic disease remains poor despite numerous treatments (including: IFN, DTIC, 5-FU, doxorubicin, somatostatin analogues, etc.).

None of which showed a benefit in terms of survival. The main therapeutic objective is still to get a palliative effect on the symptoms and / or limit a few months tumor progression.

There are many publications showing that angiogenesis is one of the major mechanisms of tumor progression in TNE. But the multiple signaling pathways involved, the existence of alternative routes and their relationship to apoptosis inducing molecules remain unknown. Sunitinib is a new molecule in the family of tyrosine kinase inhibitors targeting multiple receptors which VEGFR, KIT, PDGF-R, FLT3 and RET. Since 2006 year, Sunitinib has been approved to treat advanced kidney cancer also called advanced renal cell carcinoma (a typically chemoresistant disease for which there was no active treatment available).

Many retrospective studies in patients showing that the TNE overexpress one or more targets of sunitinib. In Phase I trial, an antitumor activity has been identified in neuroendocrine tumors. In a phase II trial including 100 patients with well-differentiated TNE and carcinoids, sunitinib is associated with a response rate of 10%, and 82% of clinical benefit in the form of tumor stability.

Currently, an international randomised phase III trial initiated in well differentiated forms, but no studies are underway for poorly-differentiated TNE.

All of this suggests that sunitinib could represent an important therapeutic option for moderate, or poorly differentiated inoperable TNE and needs to be explored in this pathology by identifying predictive biomarkers of response.

Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors

A Multicenter Phase II Open Study Coupled With a Translational Assessment of Biomarkers Predictive of Response to Sunitinib in Patients With Poorly-differentiated Advanced/Inoperable NEURO-Endocrine Tumors.

to assess the correlation between the expression of biomarkers and CT scan response. Patients are considered as responders when objective response (Partial or complete response) is showed on CT scan.

* Objective response according to RECIST criteria (Time Frame: duration of study Safety issue: No).
* Overall Survival (Time Frame: 6 months. Safety issue: No).
* Progression-free survival (PFS)
* Correlation between overall survival, PFS and tumor necrosis assessed on CT scan

correlation between the concentration of sunitinib and its major active metabolite, SU012662, and objective response and /or toxicity.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)	NCT01009593	Hepatocellular ... Hepatocellular ... Carcinoma, Hepa... Liver Diseases Neoplasms by Hi... Digestive Syste... Carcinoma Liver Neoplasms Neoplasms Neoplasms by Si... Digestive Syste... Adenocarcinoma Neoplasms, Glan...	ABT-869 Sorafenib	18 Years -	Abbott
Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)	NCT01009593	Hepatocellular ... Hepatocellular ... Carcinoma, Hepa... Liver Diseases Neoplasms by Hi... Digestive Syste... Carcinoma Liver Neoplasms Neoplasms Neoplasms by Si... Digestive Syste... Adenocarcinoma Neoplasms, Glan...	ABT-869 Sorafenib	18 Years -	Abbott
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors	NCT05208047	Advanced Gastro... Metastatic Canc...	CGT9486 plus su... CGT9486 Sunitinib Sunitinib	18 Years -	Cogent Biosciences, Inc.
Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors	NCT01215578	Neuroendocrine ... Pancreatic Neop... Advanced Diseas... Sunitinib	Sutent	18 Years -	Assistance Publique - Hôpitaux de Paris

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