Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer
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| ClinicalTrials.gov Identifier: NCT02077881 |
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Recruitment Status :
Completed
First Posted : March 4, 2014
Last Update Posted : May 28, 2020
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| 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 |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Completion Date : | October 17, 2018 |
| Arm | Intervention/treatment |
|---|---|
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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. |
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.
Other Names:
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.
Other Name: Gemzar 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). 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. Other Names:
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- 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).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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 | |
| Stanford University | |
| Palo Alto, California, United States, 94304 | |
| United States, Georgia | |
| Augusta University | |
| 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 | |
| Responsible Party: | NewLink Genetics Corporation |
| ClinicalTrials.gov Identifier: | NCT02077881 |
| Other Study ID Numbers: |
NLG2104 |
| First Posted: | March 4, 2014 Key Record Dates |
| Last Update Posted: | May 28, 2020 |
| Last Verified: | May 2020 |
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metastatic metastasis Pancreatic |
Pancreas Cancer adenocarcinoma |
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Adenocarcinoma Pancreatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine Paclitaxel Albumin-Bound Paclitaxel |
Tryptophan Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |