Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02077881|
Recruitment Status : Active, not recruiting
First Posted : March 4, 2014
Last Update Posted : July 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Pancreatic Adenocarcinoma Metastatic Pancreatic Cancer||Drug: Nab-Paclitaxel Drug: Gemcitabine Drug: Indoximod||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||157 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Indoximod in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Adenocarcinoma of the Pancreas|
|Actual Study Start Date :||August 2014|
|Actual Primary Completion Date :||January 17, 2018|
|Estimated Study Completion Date :||October 2018|
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 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.
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.
Other Name: Gemzar
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.
- Phase 2 Dosing [ Time Frame: 10 months ]
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 [ Time Frame: 10 months ]
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 [ Time Frame: 22 months ]
Phase 2 component:
To evaluate efficacy as determined by overall survival (OS) in patients with metastatic adenocarcinoma of the pancreas.
- Biomarker Response [ Time Frame: 22 months ]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 [ Time Frame: 22 months ]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 [ Time Frame: 22 months ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02077881
|United States, California|
|Palo Alto, California, United States, 94304|
|United States, Georgia|
|Augusta, Georgia, United States, 30912|
|United States, Kentucky|
|University of Kentucy|
|Lexington, Kentucky, United States, 40536|
|United States, Missouri|
|Washington University in St. Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, New Jersey|
|The Vally Hospital|
|Paramus, New Jersey, United States, 07652|
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, South Carolina|
|Greenville Health Systems|
|Greenville, South Carolina, United States, 29605|
|Gibbs Cancer Center and Research Institute|
|Spartanburg, South Carolina, United States, 29303|
|United States, Tennessee|
|The West Clinic|
|Memphis, Tennessee, United States, 38120|
|United States, Utah|
|Huntsman Cancer Center|
|Salt Lake City, Utah, United States, 84112|
|United States, Vermont|
|University of Vermont Medical Center|
|Burlington, Vermont, United States, 05401|