Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Can

Not Yet Open.

Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2017 by Emory University
Sponsor:
Emory University
Collaborators:
Merck Sharp & Dohme Corp.
Exelixis
Information provided by (Responsible Party):
Bassel El-Rayes, Emory University
ClinicalTrials.gov Identifier:
NCT03095781
First received: March 22, 2017
Last updated: March 28, 2017
Last verified: March 2017
History of Changes
Full Text View Tabular ViewNo Study Results PostedDisclaimerHow to Read a Study Record
Purpose
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.

Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Colorectal Adenocarcinoma
Metastatic Pancreatic Adenocarcinoma
Non-Resectable Cholangiocarcinoma
Non-Resectable Hepatocellular Carcinoma
Recurrent Cholangiocarcinoma
Recurrent Colorectal Carcinoma
Recurrent Gastric Carcinoma
Recurrent Hepatocellular Carcinoma
Recurrent Pancreatic Carcinoma
Recurrent Small Intestinal Carcinoma
Small Intestinal Adenocarcinoma
Stage III Colorectal Cancer
Stage III Gastric Cancer
Stage III Hepatocellular Carcinoma
Stage III Pancreatic Cancer
Stage III Small Intestinal Cancer
Stage IIIA Colorectal Cancer
Stage IIIA Gastric Cancer
Stage IIIA Hepatocellular Carcinoma
Stage IIIA Small Intestinal Cancer
Stage IIIB Colorectal Cancer
Stage IIIB Gastric Cancer
Stage IIIB Hepatocellular Carcinoma
Stage IIIB Small Intestinal Cancer
Stage IIIC Gastric Cancer
Stage IV Colorectal Cancer
Stage IV Gastric Cancer
Stage IV Hepatocellular Carcinoma
Stage IV Pancreatic Cancer
Stage IV Small Intestinal Cancer
Stage IVA Colorectal Cancer
Stage IVA Hepatocellular Carcinoma
Stage IVA Pancreatic Cancer
Stage IVB Colorectal Cancer
Stage IVB Hepatocellular Carcinoma
Stage IVB Pancreatic Cancer
Unresectable Pancreatic Carcinoma
Unresectable Small Intestinal Carcinoma
Drug: XL888
Biological: Pembrolizumab
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase Ib Trial of Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Malignancies

Resource links provided by NLM:

Genetics Home Reference related topics: cholangiocarcinoma
MedlinePlus related topics: Cancer
Drug Information available for: Pembrolizumab
Genetic and Rare Diseases Information Center resources: Stomach Cancer Small Intestinal Adenocarcinoma Small Intestine Cancer Esophageal Cancer
U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:
Recommended phase II dose of the combination of XL888 and pembrolizumab as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Cycle length 21 days. Outcome determined on day 22 (after completion of cycle 1) ]
Summary statistics will be presented. Toxicities will be presented as worst toxicity per patient and will be reported as percent toxicity.

Secondary Outcome Measures:
Overall response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: Up to 2 years after cycle 1, day 1. Cycle length is 21 days. ]
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.

Overall survival [ Time Frame: Up to 1 year after cycle 1, day 1. Each cycle is 21 days. ]
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.

Progression free survival [ Time Frame: Up to 6 months after cycle 1, day 1. Each cycle is 21 days ]
Summary statistics will be presented.

Response duration as assessed by RECIST 1.1 [ Time Frame: Up to 2 years after cycle 1, day 1. Each cycle is 21 days. ]
Summary statistics will be presented.

Other Outcome Measures:
Immune profile effects of pembrolizumab and Hsp90 inhibitor XL888 assessed in serum and tumor biopsies [ Time Frame: Up to 2 years after cycle 1, day 1. Each cycle is 21 days. ]
Summary statistics will be presented.

Estimated Enrollment: 50
Anticipated Study Start Date: September 2017
Estimated Study Completion Date: September 2023
Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pembrolizumab, XL888)
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.
Drug: XL888
Given PO
Other Names:
Heat Shock Protein 90 Inhibitor XL888
Hsp90 Inhibitor XL888
Biological: Pembrolizumab
Given IV
Other Names:
Keytruda
Lambrolizumab
MK-3475
SCH 900475

Detailed Description:
PRIMARY OBJECTIVES:

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 OBJECTIVES:

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.

Eligibility

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:

Patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, gastroesophageal junction [GEJ], cholangiocarcinoma, hepatocellular, pancreas, colorectal, small intestinal tumors) who have failed at least one prior therapy (dose escalation phase)
Patients with pancreatic adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen; eight patients must have tumors that are accessible for biopsy and sign the informed consent for paired biopsy study (dose escalation phase, arm A)
Patients with colorectal adenocarcinoma; patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and fluoropyrimidine; eight patients must have tumors that are accessible for biopsy and sign the informed consent for paired biopsy study (dose escalation phase, arm
Be willing and able to provide written informed consent/assent for the trial
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Absolute neutrophil count (ANC) ≥ 1,500 cells/µL
Platelets ≥ 100,000 cells/µL
Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) ≥ 60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
Creatinine clearance should be calculated per institutional standard
Serum total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 x ULN OR ≤ 5 x ULN for subjects with liver metastases
Albumin ≥ 2.5 mg/dL
International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Exclusion Criteria:

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Has a known history of active tuberculosis (TB) (Bacillus tuberculosis)
Hypersensitivity to pembrolizumab or history of severe allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol [PEG] 300 and polysorbate 80)
Clinically significant cardiovascular disease or peripheral vascular (e.g. myocardial infarction, unstable angina within 6 months of study entry), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia requiring medications, baseline corrected QT (QTc) > 450 msec or previous history of QT prolongation while taking other medications
Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent
Note: Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study
Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Has known history of, or any evidence of active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has known substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti-PD-L2 agent
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known active hepatitis B (e.g., hepatitis surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Has received a live vaccine within 30 days of planned start of study therapy
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03095781

Contacts
Contact: Bassel El-Rayes, MD 404-778-2670 bassel.el-rayes@emoryhealthcare.org

Locations
United States, Georgia
Emory University Hospital Midtown Not yet recruiting
Atlanta, Georgia, United States, 30308
Contact: Nikki Hirsh, MS 404-686-1855 nikkihirsh@emory.edu
Emory University/Winship Cancer Institute Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Meredith Renfroe 404-778-2670 marenfr@emory.edu
Emory Saint Joseph’s Hospital Not yet recruiting
Atlanta, Georgia, United States, 30342
Contact: Genea Crockett, MS 678-843-5911 gcrocke@emory.edu
Sponsors and Collaborators
Emory University
Merck Sharp & Dohme Corp.
Exelixis
Investigators
Principal Investigator: Bassel El-Rayes, MD Emory University/Winship Cancer Institute
More Information

Responsible Party: Bassel El-Rayes, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03095781 History of Changes
Other Study ID Numbers: IRB00087397
NCI-2016-01594 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship3321-16 ( Other Identifier: Emory University/Winship Cancer Institute )
Study First Received: March 22, 2017
Last Updated: March 28, 2017
Individual Participant Data
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Carcinoma
Pancreatic Neoplasms
Colorectal Neoplasms
Adenocarcinoma
Carcinoma, Hepatocellular
Stomach Neoplasms
Cholangiocarcinoma
Esophageal Neoplasms
Intestinal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Liver Neoplasms
Liver Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Pembrolizumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on March 31, 2017

https://clinicaltrials.gov/ct2/show/NCT03095781