Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer
A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas
1 other identifier
interventional
157
1 country
11
Brief Summary
This phase I/II trial is designed to efficiently identify the regimen limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination of the immunotherapeutic agent indoximod when administered in combination with standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. All subjects will receive the same standard gemcitabine plus nab-paclitaxel regimen, plus indoximod in doses increasing from 600 mg twice daily to, potentially, 1200 mg twice daily.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Aug 2014
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2014
CompletedFirst Posted
Study publicly available on registry
March 4, 2014
CompletedStudy Start
First participant enrolled
August 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 17, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
October 17, 2018
CompletedMay 28, 2020
May 1, 2020
3.5 years
February 28, 2014
May 26, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Phase 2 Dosing
Phase 1 component: To determine recommended phase 2 dose of indoximod when administered with a standard of care chemotherapy backbone consisting of gemcitabine plus nab-paclitaxel.
10 months
Regimen Limiting Toxicity
Phase 1 component: To identify the regimen limiting toxicity (RLT) for the combination of the immunotherapeutic agent indoximod when administered in combination with standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. RLT will be considered as only grade 3 and 4 toxicities that are attributable to the test agent and result in the delay of the administration of the backbone chemotherapy, gemcitabine plus nab-paclitaxel.
10 months
Overall Survival
Phase 2 component: To evaluate efficacy as determined by overall survival (OS) in patients with metastatic adenocarcinoma of the pancreas.
22 months
Secondary Outcomes (3)
Biomarker Response
22 months
Response Rate
22 months
Time to Progression of Disease
22 months
Study Arms (1)
Indoximod and Gemcitabine + Nab-paclitaxel
EXPERIMENTALPhase 1 portion: Participants to receive indoximod (600mg, 100mg, or 1200mg according to their assigned dose cohort) PO BID for 28 days concurrently with IV Nab-paclitaxel 125 mg/m\^2 followed by gemcitabine 1000 mg/m\^2 weekly for 3 weeks with one week rest. Each cycle is 28 days. Patients will continue until they experience disease progression or significant toxicity. Phase 2 portion: Once a RP2D is determined, treatment will commence with oral indoximod concurrent with the first backbone chemotherapy cycle.Patients will receive gemcitabine plus nab-paclitaxel on a standard 4 week cycle schedule. Oral indoximod will continue throughout.
Interventions
Nab-Paclitaxel 125 mg/m\^2 given intravenously over 30-40 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.
Gemcitabine 1000 mg/m\^2 given intravenously over 30 minutes for 3 weeks (days 1, 8 and 15) with 1 week rest. Patients will continue until they experience disease progression or significant toxicity.
Indoximod will be administered in escalating doses. Initial dosing will be 600 mg BID by mouth with escalation planned to 1200 mg BID by mouth Indoximod in the form of 200 mg capsules will be given (3, 5, and 6 capsules depending on the escalated dose). Indoximod should be taken with water by mouth one hour before breakfast and one hour prior to dinner. The medication should be taken twice daily for 28 days each cycle. Patients will continue until they experience disease progression or toxicity.
Eligibility Criteria
You may qualify if:
- Patient has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell or neuroendocrine neoplasms are excluded.
- Initial diagnosis of metastatic disease must have occurred ≤8 weeks prior to entry in the study.
- Patient has one or more metastatic tumors measurable per RECIST 1.1 by CT scan ≤4 weeks prior to entry into the study
- Male or non-pregnant and non-lactating female, and ≥18 years of age.
- Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
- Prior treatment with gemcitabine and/or nab-paclitaxel in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
- Patients cannot have received any other immunomodulatory therapies (including vaccines) as treatment for this or any other cancer.
- Patient has a Karnofsky performance status (KPS) ≥ 70.
- Patients should be asymptomatic for jaundice prior to Day 1.
You may not qualify if:
- Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease.
- Patient has known brain metastases,
- Patient has only locally advanced disease.
- Lymph node only metastases even if considered M1 disease by official staging criteria.
- History of malignancy in the last 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 3 years.
- Patients with any active autoimmune disease
- Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Stanford University
Palo Alto, California, 94304, United States
Augusta University
Augusta, Georgia, 30912, United States
University of Kentucy
Lexington, Kentucky, 40536, United States
Washington University in St. Louis
St Louis, Missouri, 63110, United States
The Vally Hospital
Paramus, New Jersey, 07652, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232, United States
Greenville Health Systems
Greenville, South Carolina, 29605, United States
Gibbs Cancer Center and Research Institute
Spartanburg, South Carolina, 29303, United States
The West Clinic
Memphis, Tennessee, 38120, United States
Huntsman Cancer Center
Salt Lake City, Utah, 84112, United States
University of Vermont Medical Center
Burlington, Vermont, 05401, United States
Related Publications (1)
Beatty GL, Delman D, Yu J, Liu M, Li JH, Zhang L, Lee JW, Chang RB, Bahary N, Kennedy EP, Wang-Gillam A, Rossi GR, Garrido-Laguna I. Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration. Clin Cancer Res. 2023 Sep 1;29(17):3514-3525. doi: 10.1158/1078-0432.CCR-23-0535.
PMID: 37534996DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2014
First Posted
March 4, 2014
Study Start
August 1, 2014
Primary Completion
January 17, 2018
Study Completion
October 17, 2018
Last Updated
May 28, 2020
Record last verified: 2020-05