Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Glioblastoma

Brain Neoplasms

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Ependymoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Amino Acids

Etoposide

Cyclophosphamide

Immunomodulating Agents

Etoposide phosphate

Ibrutinib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Patients will be treated with the 4-drug chemo-immunotherapy regimen. Cycles are a minimum of 28 days, and maximum treatment duration is 12 cycles.

Ibrutinib will be taken by mouth once daily, on days 1-21 of each treatment cycle.

Indoximod will be taken by mouth twice daily, throughout each treatment cycle.

Indoximod

Cyclophosphamide will be taken by mouth once daily, on days 1-21 of each treatment cycle.

Etoposide will be taken by mouth once daily, on days 1-21 of each treatment cycle.

Theodore S. Johnson, MD, PhD

Taylor King, RN

Theodore S Johnson, MD, PhD

Recent lab-based discoveries suggest that IDO (indoleamine 2,3-dioxygenase) and BTK (Bruton's tyrosine Kinase) form a closely linked metabolic checkpoint in tumor-associated antigen-presenting cells. The central clinical hypothesis for the GCC2020 study is that combining ibrutinib (BTK-inhibitor) with indoximod (IDO-inhibitor) during chemotherapy will synergistically enhance anti-tumor immune responses, leading to improvement in clinical response with manageable overlapping toxicity.

GCC2020 is a prospective open-label phase 1 trial to determine the best safe dose of ibrutinib to use in combination with a previously studied chemo-immunotherapy regimen, comprised of the IDO-inhibitor indoximod plus oral metronomic cyclophosphamide and etoposide (4-drug combination) for participants, age 12 to 25 years, with relapsed or refractory primary brain cancer. Those previously treated with indoximod plus temozolomide may be eligible, including prior treatment via the phase 2 indoximod study (GCC1949, NCT04049669), the now closed phase 1 study (NLG2105, NCT02502708), or any expanded access (compassionate use) protocols. A dose-escalation cohort will determine the best safe dose of ibrutinib for the 4-drug combination. This will be followed by an expansion cohort, using ibrutinib at the best safe dose in the 4-drug combination, to allow assessment of preliminary evidence of efficacy.

Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer

Repurposing Ibrutinib for Chemo-Immunotherapy in a Phase 1b Study of Ibrutinib With Indoximod Plus Metronomic Cyclophosphamide and Etoposide for Pediatric Patients With Brain Cancer

To determine the pediatric recommended phase 2 dose (RP2D) of ibrutinib, when combined with indoximod-based chemo-immunotherapy (4-drug combination therapy)

Defined as the proportion of patients with a best objective response of either complete response (CR) or partial response (PR) to evaluate preliminary evidence of efficacy of ibrutinib, when combined with indoximod-based chemo-immunotherapy (4-drug combination therapy), using "immunotherapy Response Assessment for Neuro-Oncology" (iRANO) criteria

To assess frequency, severity, and recoverability of AEs for the treatment regimen

To assess whether the immunotherapy contributes to delays in starting subsequent cycles of the chemotherapy drugs

To assess whether the immunotherapy contributes to reductions in the doses of the chemotherapy drugs

Defined as the proportion of patients with a best objective response of CR using iRANO criteria

Defined as the proportion of patients with a best objective response of PR using iRANO criteria

Defined as the proportion of patients with best objective response of complete response (CR), partial response (PR), or stable disease (SD, on at least 2 sequential study-timed MRIs) using iRANO criteria

Time of Progression-Free Survival (PFS), defined as time from study entry to progression using iRANO criteria

Augusta University

Theodore S. Johnson

Professor of Pediatrics and Co-Director of the Pediatric Immunotherapy Program

Digestive System Diseases

Gland and Hormone Related Diseases

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Gastrointestinal Agents

Pembrolizumab

Vaccines

Pancrelipase

Pancreatin

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

50, 100, 300, or 600 mg taken by mouth twice a day, every day of each cycle

Epacadostat

1x10\^9 CFU given IV on Day 2 of Cycles 3-6 (Arm A) or Day 2 of Cycles 1-6 (Arm B)

CRS-207

200 mg/m\^2 given IV on Day 1 of Cycles 1-2 (Arm A only)

5x10\^8 cells given as 6 intradermal injections on Day 2 of Cycles 1-2 (Arm A only)

GVAX

Dung Le, M.D.

This study will enroll patients who have metastatic pancreatic cancer and have progressed on prior chemotherapy.

Part 1 (dose escalation) participants will receive epacadostat/pembrolizumab/cyclophosphamide(CY)/GVAX pancreas vaccine followed by epacadostat/pembrolizumab/CRS-207, Part 1X (dose escalation) participants will receive epacadostat/pembrolizumab/CRS-207. Part 2X (dose expansion) participants will receive epacadostat/pembrolizumab/CRS-207.

The primary objectives of this study are to determine the recommended dose of epacadostat in this combination and assess survival of subjects in both treatment groups.

Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer

Phase 2 Study of Epacadostat, Pembrolizumab, and CRS-207, With or Without Cyclophosphamide and GVAX Pancreas Vaccine in Patients With Metastatic Pancreas Cancer

Evaluate 4 dose levels of epacadostat, in order to determine recommended dose for use in combination with pembrolizumab, CY, GVAX, and CRS-207

Proportion of subjects who are alive 6 months or longer after the date of randomization

Merck Sharp & Dohme LLC

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Oligodendroglioma

PF-06840003

Pfizer CT.gov Call Center

This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.

First in Patient Study for PF-06840003 in Malignant Gliomas

A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06840003 IN PATIENTS WITH MALIGNANT GLIOMAS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

DLTs: Any of the following adverse events (AE) occurring in the first cycle of treatment, unless there is a clear alternative explanation. Hematologic: Grade (Gr) 4 neutropenia lasting \>=5 days; febrile neutropenia; Gr\>=3 neutropenic with infection; Gr\>=3 thrombocytopenia with bleeding; Gr 4 thrombocytopenia. Non-Hematologic: Any toxicity attributable to PF-06840003 that resulted in administration of less than 80% of the planned doses during Cycle 1; Gr 4 non-hematologic AE; Gr 3 AE lasting \>7 days despite optimal supportive care; Gr 3 central nervous system (CNS) AE regardless of duration; Gr 3 QTc prolongation (QTc \>500 milliseconds) (a DLT only if persisting after correction of any reversible causes); Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3\*upper limit of normal (ULN) and total bilirubin \>2\*ULN.

An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.

Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

Objective response rate (ORR), defined as the percentage of patients achieving complete response (CR) or partial response (PR) as assessed by Macdonald criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks.

Disease control rate (DCR) was defined as the percentage of patients achieving CR, PR, or stable disease (SD). Overall DCR was based on iRANO criteria: CR: complete disappearance of all enhancing measurable and non-measurable disease on consecutive MRI at least 4 weeks apart, off steroid, sustained for at least 4 weeks; PR: \>=50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; SD: does not qualify for CR, PR, or progression disease, and stable clinically.

Following parameters were analyzed for hematology laboratory test: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, and absolute basophils. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.

Following parameters were analyzed for chemistry laboratory test: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, and phosphorous or phosphate. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.

Vital signs included measurements of blood pressure and temperature (oral, tympanic, temporal or axillary). The investigator judged any clinically significant vital signs findings.

Cmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data.

Tmax of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) were observed directly from data as time of first occurence.

AUClast of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.

AUCtau of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by linear/log trapezoidal method.

CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.

Vz/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/(AUC\*kel). AUC is the area under concentration curve and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.

t1/2 of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.

AUCinf of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUClast + (Clast/kel), where AUClast is the area under the concentration-time profile from time zero to the time of the last quantifiable concentration, Clast is the predicted serum concentration at the last quantifiable time point estimated from the log linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.

Cmin of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.

Cav of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was observed directly from data.

CL/F of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by Dose/Area under the concentration-time profile from time 0 extrapolated to infinite time (AUCinf).

Rac of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCtau (single dose).

Rss of PF-06840002 (Active Enantiomer) and PF-06840001 (Inactive Enantiomer) was determined by AUCtau (steady state) / AUCinf (single dose). The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.

Steady-State trough level ratio was determined by cerebrospinal fluid (CSF)/Plasma. CSF/Plasma ratio was calculated based on the unbound concentration of each analyte. The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest.

The levels of Kynurenine and Tryptophan in blood samples were determined using the qualified analytical method.

The Kynurenine/Tryptophan ratio was determined by 1000\*Kynurenine/Tryptophan.

Pfizer

The same event may appear as both an AE and an SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

PF-06840003 (formulated 125 mg tablets) was administered orally at 125 mg once daily (QD) for 28-day cycles.

PF-06840003 125 MG QD

PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg QD for 28-day cycles.

PF-06840003 250 MG QD

PF-06840003 (formulated 125 mg tablets) was administered orally at 250 mg twice daily (BID) for 28-day cycles.

PF-06840003 250 MG BID

PF-06840003 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles.

PF-06840003 500 MG BID

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

All Part 1 enrolled participants who received at least 1 dose of study treatment.

Part 2 of the study was not initiated. Because after reviewing efficacy, safety, PK and PD of all available data from enrolled patients, the Sponsor decided to prematurely terminate the study.

Pfizer ClinicalTrials.gov Call Center

Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]

All-causality TEAEs

Treatment-related TEAEs

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]

Grade 3 or 4

Grade 5

Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]

Week 8

Week 16

Week 24

The analysis population included all the participants enrolled.

Objective Response Rate (ORR) [Part 1]

Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1]

Anemia, Grade 0

Anemia, Grade 1

Anemia, Grade 2

Hemoglobin increased, Grade 0

Lymphocyte count increased, Grade 0

Lymphopenia, Grade 0

Lymphopenia, Grade 1

Lymphopenia, Grade 2

Lymphopenia, Grade 3

Neutrophils (absolute), Grade 0

Neutrophils (absolute), Grade 1

Neutrophils (absolute), Grade 2

Platelets, Grade 0

Platelets, Grade 1

WBC, Grade 0

WBC, Grade 1

WBC, Grade 2

Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]

ALT, Grade 0

ALT, Grade 1

ALT, Grade 3

ALT, Grade 4

Alkaline phosphatase, Grade 0

Alkaline phosphatase, Grade 1

AST, Grade 0

AST, Grade 2

AST, Grade 4

Bilirubin (total), Grade 0

Creatinine, Grade 0

Creatinine, Grade 1

Creatinine, Grade 2

Hypercalcemia, Grade 0

Hypercalcemia, Grade 1

Hyperglycemia, Grade 0

Hyperglycemia, Grade 1

Hyperglycemia, Grade 2

Hyperglycemia, Grade 3

Hyperkalemia, Grade 0

Hyperkalemia, Grade 3

Hypermagnesemia, Grade 0

Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer	NCT05106296	Ependymoma Medulloblastoma Glioblastoma Primary Brain T...	Ibrutinib Indoximod Cyclophosphamid... Etoposide	12 Years - 25 Years	Augusta University
Chemo-immunotherapy Using Ibrutinib Plus Indoximod for Patients With Pediatric Brain Cancer	NCT05106296	Ependymoma Medulloblastoma Glioblastoma Primary Brain T...	Ibrutinib Indoximod Cyclophosphamid... Etoposide	12 Years - 25 Years	Augusta University
Epacadostat, Pembrolizumab, and CRS-207, With or Without CY/GVAX Pancreas in Patients With Metastatic Pancreas Cancer	NCT03006302	Metastatic Panc...	Epacadostat Pembrolizumab CRS-207 CY GVAX	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
First in Patient Study for PF-06840003 in Malignant Gliomas	NCT02764151	Oligodendroglio... Astrocytoma Malignant Gliom...	PF-06840003	18 Years -	Pfizer
Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer	NCT02460367	Non-small Cell ... Progression of ... Non-small Cell ...	Docetaxel Tergenpumatucel... Indoximod	18 Years -	Lumos Pharma
Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer	NCT02460367	Non-small Cell ... Progression of ... Non-small Cell ...	Docetaxel Tergenpumatucel... Indoximod	18 Years -	Lumos Pharma
Immunotherapy Combination Study in Advanced Previously Treated Non-Small Cell Lung Cancer	NCT02460367	Non-small Cell ... Progression of ... Non-small Cell ...	Docetaxel Tergenpumatucel... Indoximod	18 Years -	Lumos Pharma

Spots Global Cancer Trial Database for ido

Every month we try and update this database with for ido 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 ido

Every month we try and update this database with for ido 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 ido 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.