Neoplasms

Digestive System Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Rare Diseases

Gastrointestinal Stromal Tumors

Disease Progression

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Quality of Life

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Immunomodulating Agents

Atezolizumab

Tyrosine Kinase Inhibitors

Imatinib Mesylate

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib per os 400 mg daily continuously associated with intravenous administrations of atezolizumab at the fixed dose of 1 200 mg every 3 weeks (up to 12 months)

Imatinib alone, per os 400 mg daily continuously (up to 12 months)

Atezolizumab 1200 mg

Imatinib 400 MG

Julien GAUTIER

Mehdi BRAHMI, MD

Antoine ITALIANO

Loïc LEBELLEC

Florence DUFFAUD, MD

Agnès DUCOULOMBIER

Nicolas ISAMBERT

Olivier BOUCHE, MD

Marc PRACHT

Emmanuelle BOMPAS

Justine GANTZER, MD

Axel LE CESNE, MD

This trial is a prospective, randomized (1:1 ratio), multicenter, comparative and phase II study, conducted in patients with unresectable advanced gastrointestinal stromal tumors (GIST) after failure of imatinib (disease progression),sunitinib and regorafenib (either disease progression or intolerance)

In the first arm, patients will be treated with imatinib + atezolizumab (experimental arm), whereas in the second arm, patients will be treated with imatinib alone (control arm).

The comparison between this two arms will allow to compare whether or not atezolizumab and imatinib is efficient for disease control, in terms of Progression-Free Survival improvement.

This is a prospective, randomized (1:1 ratio), multicenter, comparative and phase II trial.

Patients with unresectable advanced gastrointestinal stromal tumors (GIST) will be accrued after the failure of standard treatments (imatinib, sunitinib and regorafenib) :

* For imatinib, failure is defined as disease progression
* For sunitinib and regorafenib, failure is defined as disease progression and/or intolerance

Randomization (1:1 ratio) will be stratified according to:

* The tumor KIT (exon 11) mutational status: wild type or mutated

STUDY TREATMENTS :

During the treatment period (12 months maximum), all patients will receive either:

* Imatinib per os 400 mg daily continuously associated with intravenous administrations of atezolizumab at the fixed dose of 1200 mg every 3 weeks (experimental arm)
* Or imatinib alone, per os 400 mg daily continuously (control arm)

The comparison between this two arms will allow to compare whether or not atezolizumab and imatinib is efficient for disease control, in terms of Progression-Free Survival improvement.

STATISTICAL ANALYSIS :

A total of 110 patients will be randomized (55 per arm).

It is expected a 6-month PFS rate of 10% in the standard arm (imatinib alone). Thus, a 6-month PFS-rate of 30% is a clinically significant target for patient treated with imatinib associated to immunotherapy.

An interim safety analysis is planned to be conducted after 6-month follow-up of the 12th patient has been randomized (approximately 6 patients by arm).

PFS will be estimated using the Kaplan-Meier method, and will be described in terms of median PFS along with the associated 2-sided 95% CIs for the estimates.

PFS distributions will be compared between the 2 study arms using a stratified Log-Rank test by tumor mutational status of KIT - exon 11 (stratification factors used for the randomisation).

DATA ENTRY, DATA MANAGEMENT AND STUDY MONITORING :

All the data concerning the patients will be recorded in the electronic case report form (eCRF) throughout the study. Serious adverse event (SAE) and Adverse Event of Specific Interest (AESI) reporting will be also paper-based by e-mail and/or Fax.

The sponsor will perform the study monitoring and will help the investigators to conduct the study in compliance with the clinical trial protocol, Good Clinical Practices (GCP) and local law requirements.

A Prospective, Randomized, Multicenter, Comparative Study of the Efficacy of Imatinib Resumption Combined With Atezolizumab Versus Imatinib Resumption Alone in Patients With Unresectable Advanced Gastrointestinal Stromal Tumors (GIST) After Failure of Standard Treatments

Time from the date of randomization to the date of first disease progression, or death from any cause, whichever occurs first

The best response from randomization : Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD)

The proportion of patients with a best overall response of CR or PR during the study

The time from the date of randomization to the date of permanent study treatments discontinuation (any cause, including death, progression, discontinuation of treatment due to progression, toxicity or start of a new anticancer therapy and withdrawal of consent)

The time from the date of randomization to the date of death due to any cause

Assessed using the EORTC QLQ-C30 questionnaire

Described through the incidence and severity of drug-related AEs (AE, SAE, SUSAR, new safety issue) according to the National Cancer Institute Common Terminology Criteria for Adverse Event Version 5 (NCI-CTC AE V5.0)

Centre Leon Berard

Nervous System Diseases

Heart and Blood Diseases

Wounds and Injuries

Sarcoma

Hematoma, Subdural

Soft Tissue Sarcoma

Mitogens

Patients receive rogaratinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and CT, MRI, and PET-CT every 8 weeks. Patients may also undergo blood sample collection on study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Rogaratinib

Suzanne George

This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To estimate the objective radiographic response rate to single agent rogaratinib (BAY 1163877) in two cohorts of patients with sarcoma: Cohort A defined as patients with a sarcoma which harbors an alteration in fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4 identified by next-generation sequencing profiling, and Cohort B defined as patients with advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST).

SECONDARY OBJECTIVES:

I. To estimate progression-free survival (PFS) in patients in Cohort A and Cohort B treated with rogaratinib (BAY 1163877).

II. Further assessment for safety and tolerability.

EXPLORATORY OBJECTIVES:

I. To evaluate serial measurements of FGFR and FGFR ligand in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing (RNA-seq) (pre-treatment biopsy and post-progression biopsy \[if available\]).

II. Whole exome sequencing (WES) of the pre-treatment biopsy and post-progression biopsy (if available) to help identify mechanisms of resistance.

III. To bank tumor material, germline deoxyribonucleic acid (DNA), and peripheral blood for potential future research for participating subjects who provide additional consent.

IV. To explore rogaratinib exposure with pharmacodynamics effects (i.e., clinical response, toxicity, and markers of FGFR pathway inhibition).

OUTLINE:

Patients receive rogaratinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo biopsy at baseline and progression and computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT every 8 weeks. Patients may also undergo blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days.

Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)

Phase 2 Study of Rogaratinib (BAY 1163877) in the Treatment of Patients With Sarcoma Harboring Alterations in Fibroblast Growth Factor Receptor (FGFR) 1-4 and SDH-Deficient Gastrointestinal Stromal Tumor (GIST)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be evaluated in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing. Estimation of continuous biomarker measures will be via mean or median as appropriate and standard deviation.

Will identify mechanisms of resistance via whole exome sequencing of pre- and post-treatment biopsies and considered exploratory.

The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Will be estimated using Kaplan-Meier method.

Adverse events will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

National Cancer Institute (NCI)

Nilotinib

Novartis Pharmaceuticals

This study will assess time-to-disease progression in patients with advanced gastrointestinal stromal tumor (GIST) previously treated with imatinib ≥600 mg.

Evaluation of Nilotinib In Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

Evaluation of Nilotinib In Patients With Advanced Gastrointestinal Stromal Tumor (GIST) Previously Treated With Imatinib

Sunitinib

cabozantinib

Patrick Schöffski, MD

The study is a multi-center, multi-national, open label, single arm Phase II study of single-agent cabozantinib. The objective of the study is to assess the safety and activity of cabozantinib in patients with metastatic GIST who have previously progressed on imatinib and sunitinib and have not been exposed yet to other KIT- or PDGFR-directed tyrosine kinase inhibitors.

Patient will receive cabozantinib until they experience no further benefit from the treatment, becoming intolerant to the drug or wishing to discontinue the treatment. Treatment beyond RECIST 1.1 progression is allowed in patients deriving clinical benefit upon investigator's discretion, provided no other criteria for treatment withdrawal are met.

Ph II CABOGIST in GIST

Phase II Study of Cabozantinib in Patients With Gastrointestinal Stromal Tumor (GIST) Who Progressed During Neoadjuvant, Adjuvant or Palliative Therapy With Imatinib and Sunitinib

Prevalence of different mutational subtypes of GIST in archived tumor material derived from the primary tumor or a metastatic site and relative efficacy of cabozantinib in recruited mutational subsets

Feasibility of using circulating plasma DNA as "liquid biopsy" for mutational analysis in metastatic GIST with assessment of the concordance of results with conventional tissue-based mutational analysis

assessed with independent central review of radiological images

assessed with independent central review of radiological images.

Time to treatment failure (TTF) defined as treatment beyond progression is allowed by the protocol at the discretion of the treating physician)

Safety will be graded according to the Common Terminology Criteria (CTC) for Adverse Events (AE), CTC-AE version 4.0

European Organisation for Research and Treatment of Cancer - EORTC

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Patients receive ipilimumab IV over 90 minutes on day 1 and imatinib mesylate PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

David S Hong

This phase I trial studies the side effects and best dose of ipilimumab and imatinib mesylate in treating patients with solid tumors that have spread to other places in the body or cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ipilimumab and imatinib mesylate may work better in treating patients with solid tumors.

PRIMARY OBJECTIVES:

I. To evaluate the safety and toxicity profile of intravenous ipilimumab (Yervoy) administered in combination with oral imatinib mesylate (GLEEVEC) for patients with advanced malignancies that are refractory to standard therapy, relapsed after standard therapy, or have no available standard therapy.

II. To determine the maximum toxic dose (MTD) and dose limiting toxicities (DLT) of ipilimumab and imatinib mesylate combination therapy.

SECONDARY OBJECTIVES:

I. To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy.

II. To determine antitumor activity of ipilimumab and imatinib mesylate combination therapy in KIT confirmed solid tumors.

III. To evaluate the potential predictive role of tumor-associated immune biomarkers for therapy effectiveness.

IV. To evaluate the potential predictive role of therapy associated toxicities with antitumor activity.

OUTLINE: This is a dose-escalation study.

Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1 and imatinib mesylated orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Ipilimumab and Imatinib Mesylate in Advanced Cancer

A Phase I Trial of Ipilimumab (Immunotherapy) and Imatinib Mesylate (c-Kit Inhibitor) in Patients With Advanced Malignancies

MTD determined as the highest dose level with less than 2 patients with dose limiting toxicity (DLT) out of at least six patients in the cohort. DLT determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Prospective, Randomized, Multicenter, Comparative Study of the Efficacy of Imatinib Resumption Combined With Atezolizumab Versus Imatinib Resumption Alone in Patients With Unresectable Advanced Gastrointestinal Stromal Tumors (GIST) After Failure of Standard Treatments	NCT05152472	Unresectable Ga... Locally Advance... Metastatic Gast...	Atezolizumab 12... Imatinib 400 MG	18 Years -	Centre Leon Berard
Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)	NCT04595747	Locally Advance... Locally Advance... Metastatic Gast... Metastatic Sarc... Stage III Gastr... Stage III Small... Stage IV Gastri... Stage IV Small ...	Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Positron Emissi... Rogaratinib	18 Years -	National Cancer Institute (NCI)
Evaluation of Nilotinib In Patients With Advanced Gastrointestinal Stromal Tumor (GIST)	NCT01110668	Gastrointestina...	Nilotinib	18 Years -	Novartis
Ph II CABOGIST in GIST	NCT02216578	Metastatic Gast...	cabozantinib	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Ipilimumab and Imatinib Mesylate in Advanced Cancer	NCT01738139	Advanced Malign... C-KIT Tyrosine ... Clinical Stage ... Metastatic Gast... Metastatic Mali... Metastatic Mela... Pathologic Stag... Unresectable Me... Unresectable So...	Imatinib Mesyla... Ipilimumab	15 Years -	M.D. Anderson Cancer Center
Ipilimumab and Imatinib Mesylate in Advanced Cancer	NCT01738139	Advanced Malign... C-KIT Tyrosine ... Clinical Stage ... Metastatic Gast... Metastatic Mali... Metastatic Mela... Pathologic Stag... Unresectable Me... Unresectable So...	Imatinib Mesyla... Ipilimumab	15 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for metastatic gastrointestinal stromal tumor