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Gastrointestinal Neoplasms

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Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

XL888

Maria Diab, MD

This phase Ib trial studies the side effects and best dose of Hsp90 inhibitor XL888 when given together with pembrolizumab in treating patients with advanced gastrointestinal cancer that has spread to other places in the body. XL888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving XL888 with pembrolizumab may work better in treating patients with gastrointestinal cancer.

PRIMARY OBJECTIVE:

I. Determine the recommended phase II dose for the combination of XL888 and pembrolizumab.

SECONDARY OBJECTIVES:

I. Define the toxicity profile of the combination of XL888 and pembrolizumab.

II. Evaluate the activity of the combination of XL888 and pembrolizumab in previously treated patients with gastrointestinal tumors.

TERTIARY OBJECTIVE:

I. Evaluate the effect of the combination on the immune profile in the serum and in tumor biopsies.

OUTLINE: This is a dose-escalation study of Hsp90 inhibitor XL888.

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and XL888 orally (PO) on day 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

Phase Ib Trial of Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Malignancies

Summary statistics will be presented. Toxicities will be presented as worst toxicity per patient and will be reported as percent toxicity.

RECIST version 1.1 will be used in this study for assessment of tumor response. While either CT or MRI may be utilized, as per RECIST 1.1, CT is the preferred imaging technique in this study.

Once a subject experiences confirmed disease progression or starts a new anti-cancer therapy, the subject moves into the survival follow-up phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the study, whichever occurs first.

Merck Sharp & Dohme LLC

Exelixis

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Emory University

Principal Investigator

Skin and Connective Tissue Diseases

Melanoma

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

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

The treatment period will include dosing (taking a certain amount on a regular schedule) with vemurafenib along with the study drug, XL888. Everyone in the study will receive both drugs, but the XL888 will be given at different doses (different amounts). Everyone in this study will be given vemurafenib at the standard dose (the amount of the drug that is given as standard treatment) of 960 milligrams (mg) twice per day, unless the first people in the study have severe side effects when taking the lowest dose of XL888 along with vemurafenib. If that happens, the next people in the study may be given a lower dose of vemurafenib (720 mg twice per day) along with the lowest dose of XL888.

Level -1: XL888 30 mg; Level 1: XL888 30 mg; Level 2: XL888 45 mg; Level 3: XL888 90 mg; Level 4: XL888 135 mg

Level -1: Vemurafenib 720 mg; Level 1: Vemurafenib 960 mg; Level 2: Vemurafenib 960 mg; Level 3: Vemurafenib 960 mg; Level 4: Vemurafenib 960 mg

Zeynep Eroglu, M.D.

This is a multi-cohort, dose-escalation study of XL888 with a fixed dose of vemurafenib. New dose escalation or de-escalation cohorts will be assigned by the Principal Investigator (PI) with discussion with appropriate co-investigators once safety and tolerability is known for a given cohort in accordance to dose escalation rules. Participants will be defined to be enrolled within a cohort upon receipt of first dose of XL888/vemurafenib.

In this study, the investigational drug XL888 will be given along with the drug vemurafenib. The investigators want to learn more about the safety and side effects of XL888 and hope to find out what dose of the drug can be given safely without serious side effects. Based on research done in a laboratory on tissue samples (cells collected from living things), the researchers think that XL888 might help to make vemurafenib work to fight cancer cells in the body for a longer period of time.

Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma

Phase I Study of Escalating Doses of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma

MTD and RP2D of XL888 when administered orally with vemurafenib to patients with BRAF V600 mutated melanoma, and evaluate the safety and tolerability of this combination. Safety will be assessed by evaluation of adverse events (AEs), vital signs, electrocardiogram (ECG), laboratory tests and concomitant medications. Adverse event terms recorded on the case report forms (CRFs) will be standardized using the Medical Dictionary for Regulatory Activities (MedDRA). Severity grade will be defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Summaries will be directed toward treatment-emergent adverse events (TEAEs), defined as events that start or worsen after the first dose of study treatment. TEAEs will be tabulated in accordance with system organ class and preferred term by overall incidence, worst reported severity, and relationship to study treatment.

Progression Free Survival at 6 months. The median time and its 95% confidence intervals will be estimated using the Kaplan-Meier method for the same cohort. The corresponding Kaplan-Meier curves will also be generated.

Overall Survival at 1 year. The median time and its 95% confidence intervals will be estimated using the Kaplan-Meier method for the same cohort. The corresponding Kaplan-Meier curves will also be generated.

The best overall response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation. In general, the patient's best response assignment will depend on findings of both target and non-target disease and will also take into consideration the appearance of new lesions. Tumor response for all participants will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST, V1.1).

H. Lee Moffitt Cancer Center and Research Institute

Escalating Doses of XL888 with Vemurafenib plus Cobimetinib.

Level 1: XL888 30 mg by mouth (PO) twice weekly (BIW). Level 2: XL888 45 mg PO BIW.

Level 3: XL888 60 mg PO BIW. Level 4: XL888 90 mg PO BIW.

Vemurafenib 720 mg by mouth twice a day (BID)

Cobimetinib 40 mg by mouth once daily (QD). Administered 3 weeks on, 1 week off.

Cobimetinib

The main purpose of this study is to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of XL888 when administered orally with vemurafenib plus cobimetinib in participants with BRAF V600 mutated melanoma and to evaluate the safety and tolerability of this combination.

XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma

Phase I Study of Escalating Doses of XL888 With Vemurafenib Plus Cobimetinib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma

The maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of XL888 when administered orally with vemurafenib plus cobimetinib in patients with BRAF V600 mutated melanoma.

Genentech, Inc.

The purpose of this study is to evaluate the safety and tolerability of XL888 in subjects with solid tumors. XL888 is a potent and selective inhibitor of HSP90, a key component of a molecular chaperone complex that promotes the conformational maturation and stabilization of diverse client proteins. Many HSP90 client proteins play critical roles in signaling pathways implicated in tumor cell growth, proliferation, and survival.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer	NCT03095781	Colorectal Aden... Metastatic Panc... Recurrent Color... Recurrent Pancr... Stage III Color... Stage III Pancr... Stage IIIA Colo... Stage IIIB Colo... Stage IV Colore... Stage IV Pancre... Stage IVA Color... Stage IVA Pancr... Stage IVB Color... Stage IVB Pancr... Unresectable Pa...	XL888 Pembrolizumab	18 Years -	Emory University
Study of XL888 With Vemurafenib for Patients With Unresectable BRAF Mutated Stage III/IV Melanoma	NCT01657591	Melanoma	XL888 Vemurafenib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma	NCT02721459	Melanoma Skin Cancer	XL888 Vemurafenib Cobimetinib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer	NCT03095781	Colorectal Aden... Metastatic Panc... Recurrent Color... Recurrent Pancr... Stage III Color... Stage III Pancr... Stage IIIA Colo... Stage IIIB Colo... Stage IV Colore... Stage IV Pancre... Stage IVA Color... Stage IVA Pancr... Stage IVB Color... Stage IVB Pancr... Unresectable Pa...	XL888 Pembrolizumab	18 Years -	Emory University
XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma	NCT02721459	Melanoma Skin Cancer	XL888 Vemurafenib Cobimetinib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Safety Study of Pharmacokinetics of XL888 in Adults With Solid Tumors	NCT00796484	Cancer	XL888	18 Years -	Exelixis
Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer	NCT03095781	Colorectal Aden... Metastatic Panc... Recurrent Color... Recurrent Pancr... Stage III Color... Stage III Pancr... Stage IIIA Colo... Stage IIIB Colo... Stage IV Colore... Stage IV Pancre... Stage IVA Color... Stage IVA Pancr... Stage IVB Color... Stage IVB Pancr... Unresectable Pa...	XL888 Pembrolizumab	18 Years -	Emory University
XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma	NCT02721459	Melanoma Skin Cancer	XL888 Vemurafenib Cobimetinib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for xl888

Every month we try and update this database with for xl888 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for xl888

Every month we try and update this database with for xl888 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for xl888 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.