Study Of IDO Inhibitor In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Cancer

Study Overview

Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

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.

This is a Phase I/II trial designed to evaluate the combination of the immunotherapeutic agent indoximod and the standard of care chemotherapy gemcitabine plus nab-paclitaxel in subjects with metastatic adenocarcinoma of the pancreas. The phase 1 portion is designed to identify the regimen-limiting toxicity (RLT) and recommended phase 2 dose (RP2D) for the combination. The phase 2 portion of the study will evaluate the potential efficacy of this combination. All subjects will receive the standard 28-day gemcitabine plus nab-paclitaxel regimen. Twice daily oral indoximod will be administered concurrently in continuous 28 day cycles. In the phase 1 portion, dose escalation of indoximod will begin at 600 mg twice a day and potentially escalate to 1200 mg twice a day. There will be no intra-subject dose escalation. Regimen-limiting toxicity will be considered as those toxicities related to indoximod that significantly limit the administration of the backbone chemotherapy gemcitabine plus nab-paclitaxel. The period for determination of dose-limiting toxicities will be the initial 28 days of treatment. The recommended phase 2 dose will include an assessment of toxicities that occur at later time points. Once a RP2D is determined, the phase 2 portion of the study will be initiated. In both phase 1 and phase 2, every 2 cycles subjects will have repeat imaging to assess response. Corollary biomarkers will be assessed at the same interval as will PET-CT after the 1st 8 week cycle. Up to 18 patients will be enrolled in the phase 1 portion of the study and 80 patients will be enrolled in the phase 2 portion.

Metastatic Pancreatic Adenocarcinoma
Metastatic Pancreatic Cancer

DRUG: Nab-Paclitaxel
DRUG: Gemcitabine
DRUG: Indoximod

NLG2104

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2014-02-28	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-05-26
First Submitted that Met QC Criteria 2014-02-28	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-05-28
First Posted (ACTUAL) 2014-03-04	Results First Posted N/A	Last Verified 2020-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Indoximod and Gemcitabine + Nab-paclitaxel Phase 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 re	DRUG: Nab-Paclitaxel 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. DRUG: Gemcitabine 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. DRUG: Indoximod 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).

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Indoximod and Gemcitabine + Nab-paclitaxel

Phase 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 re

DRUG: Nab-Paclitaxel

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.

DRUG: Gemcitabine

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.

DRUG: Indoximod

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).

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Biomarker Response	A secondary objective is to examine biomarker responses of gemcitabine and nab-paclitaxel with indoximod through the evaluation of serum for biomarkers of IDO activity (kynurenine and tryptophan), before and after initiation of therapy through specimen collection at protocol specified timepoints.	22 months
Response Rate	To determine the response rate of the combination indoximod with gemcitabine plus nab-paclitaxel. Imaging assessments to be performed at protocol-specified time points and evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).	22 months
Time to Progression of Disease	To determine the time to progression with the combination indoximod with gemcitabine plus nab-paclitaxel. Progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).	22 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Learn

Resources

PatientS

Caregivers

Clinical Trial Record