Back to resultsStudy of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer
Primary Purpose
Metastatic Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nab-Paclitaxel
Gemcitabine
Indoximod
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Pancreatic Adenocarcinoma focused on measuring metastatic, metastasis, Pancreatic, Pancreas, Cancer, adenocarcinoma
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Stanford University
- Augusta University
- University of Kentucy
- Washington University in St. Louis
- The Vally Hospital
- University of Pittsburgh Medical Center
- Greenville Health Systems
- Gibbs Cancer Center and Research Institute
- The West Clinic
- Huntsman Cancer Center
- University of Vermont Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Indoximod and Gemcitabine + Nab-paclitaxel
Arm Description
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 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.
Outcomes
Primary Outcome Measures
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.
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.
Overall Survival
Phase 2 component:
To evaluate efficacy as determined by overall survival (OS) in patients with metastatic adenocarcinoma of the pancreas.
Secondary Outcome Measures
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.
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).
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).
Full Information
NCT ID
NCT02077881
First Posted
February 28, 2014
Last Updated
May 26, 2020
Sponsor
NewLink Genetics Corporation
1. Study Identification
Unique Protocol Identification Number
NCT02077881
Brief Title
Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer
Official Title
A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
August 2014 (Actual)
Primary Completion Date
January 17, 2018 (Actual)
Study Completion Date
October 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NewLink Genetics Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer
Keywords
metastatic, metastasis, Pancreatic, Pancreas, Cancer, adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
157 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Indoximod and Gemcitabine + Nab-paclitaxel
Arm Type
Experimental
Arm Description
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 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.
Intervention Type
Drug
Intervention Name(s)
Nab-Paclitaxel
Other Intervention Name(s)
Abraxane, Paclitaxel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Indoximod
Other Intervention Name(s)
1-methyl-D-tryptophan, D-1MT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Phase 2 Dosing
Description
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.
Time Frame
10 months
Title
Regimen Limiting Toxicity
Description
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.
Time Frame
10 months
Title
Overall Survival
Description
Phase 2 component:
To evaluate efficacy as determined by overall survival (OS) in patients with metastatic adenocarcinoma of the pancreas.
Time Frame
22 months
Secondary Outcome Measure Information:
Title
Biomarker Response
Description
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.
Time Frame
22 months
Title
Response Rate
Description
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).
Time Frame
22 months
Title
Time to Progression of Disease
Description
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).
Time Frame
22 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Kentucy
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Vally Hospital
City
Paramus
State/Province
New Jersey
ZIP/Postal Code
07652
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Greenville Health Systems
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Gibbs Cancer Center and Research Institute
City
Spartanburg
State/Province
South Carolina
ZIP/Postal Code
29303
Country
United States
Facility Name
The West Clinic
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Huntsman Cancer Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer
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