Trial record 1 of 1 for:    NCT02077881
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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02077881
Recruitment Status : Recruiting
First Posted : March 4, 2014
Last Update Posted : June 20, 2017
Information provided by (Responsible Party):
NewLink Genetics Corporation

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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Metastatic Pancreatic Cancer Drug: Nab-Paclitaxel Drug: Gemcitabine Drug: Indoximod Phase 1 Phase 2

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 600mg/day and potentially escalate to 1200mg/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)
Estimated Enrollment : 98 participants
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
Study Start Date : August 2014
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 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:
  • Abraxane
  • Paclitaxel
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:
  • 1-methyl-D-tryptophan
  • D-1MT

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data. 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 (or MRI, if patient is allergic to CT contrast media). Patients cannot have nodal metastases alone even if such nodal metastases are formally considered M1 disease
  • Life expectancy of greater than 3 months.
  • Male or non-pregnant and non-lactating female, and ≥18 years of age.
  • If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test (β-hCG) documented within 7 days prior to the first administration of study drug.
  • The effects of indoximod on the developing human fetus are unknown. For this reason and because indoximod may affect maternal immune tolerance of the fetus, sexually active women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Use of contraception or abstinence should continue for a minimum of 1 month after completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should discontinue the study drug and inform her treating physician immediately. Also men should be discouraged from fathering children while on treatment.
  • 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 adequate biological parameters as demonstrated by the following blood counts at Baseline (obtained ≤14 days prior to treatment initiation):
  • Absolute neutrophil count (ANC) ≥1.5 × 10^9/L
  • Platelet count ≥75,000/mm3 (75 × 10^9/L)
  • Hemoglobin (Hgb) ≥9 g/dL.
  • Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to randomization):
  • AST (SGOT), ALT (SGPT) ≤2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤5 × ULN is allowed
  • Total bilirubin ≤ULN, patients with known Gilbert's syndrome allowed up to 3x ULN.
  • Serum creatinine within normal limits or calculated clearance ≥60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value
  • Patient has acceptable coagulation studies (obtained ≤14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (±15%). If the patient is on coumadin we suggest switching the patient to a low molecular weight heparin product including enoxaparin (Lovenox) and fondiparinux (Arixtra), but if not feasible then INR must be ≤ 3.
  • Patient has no clinically significant abnormalities in urinalysis results (obtained ≤14 days prior to randomization).
  • Patient has a Karnofsky performance status (KPS) ≥ 70.
  • Patients should be asymptomatic for jaundice prior to Day 1.
  • Significant or symptomatic amounts of ascites should be drained prior to enrollment.
  • Pain symptoms should be stable and should not require modifications in analgesic management prior to enrollment.
  • Ability to understand and the willingness to sign a written informed consent document.

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.
  • Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  • Patient has known historical or active infection with HIV, hepatitis B, or hepatitis C.
  • Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic dermatitis, asthma, IBD, M.S., uveitis, vasculitis), chronic inflammatory condition, or any condition requiring concurrent use of any systemic immunosuppressants or steroids for any reason would be excluded from the study. Any patient with an allo-transplant of any kind would be excluded as well. This would include those with a xenograft heart valve to avoid the potential risk of any immune reaction causing valvular degeneration. Mild-intermittent asthma requiring only occasional beta-agonist inhaler use or mild localized eczema will not be excluded.
  • 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.
  • Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study, breastfeeding should be discontinued.

Information from the National Library of Medicine

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 identifier (NCT number): NCT02077881

United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Benjamin Priestley    650-723-2990      
Principal Investigator: Sigurdis Haraldsdottir, MD, PhD         
United States, Georgia
Georgia Regents University Recruiting
Augusta, Georgia, United States, 30912
Contact: Robbin Dobbins, RN    706-721-2154   
Principal Investigator: Samir Khleif, MD         
United States, Kentucky
University of Kentucy Recruiting
Lexington, Kentucky, United States, 40536
Contact: Stephanie Malicote    404-785-0232      
Principal Investigator: Peter Hosein, MD         
United States, Missouri
Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Kimberly Lears    314-747-8085   
Principal Investigator: Andrea Wang-Gillam, MD         
United States, New Jersey
The Vally Hospital Recruiting
Paramus, New Jersey, United States, 07652
Contact: Stephanie Blash    201-634-5792      
Principal Investigator: Jin Lee, MD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Natalie Streeter    412-235-1276   
Principal Investigator: Nathan Bahary, MD         
United States, South Carolina
Greenville Health Systems Recruiting
Greenville, South Carolina, United States, 29605
Contact: Lisa Johnson, RN    864-455-3600      
Contact: Jill Cantrell, RN         
Principal Investigator: Mark O'Rourke, MD         
Gibbs Cancer Center and Research Institute Recruiting
Spartanburg, South Carolina, United States, 29303
Contact: Kenneth Kuenzli, RN    864-560-7579      
Principal Investigator: Caio Rocha-Lima, MD         
United States, Tennessee
The West Clinic Recruiting
Memphis, Tennessee, United States, 38120
Contact: Cindy Inman, RN    901-683-0055   
Principal Investigator: Bradley Somer, MD         
United States, Utah
Huntsman Cancer Center Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Rachel Kingsford, MS    801-585-0115   
Principal Investigator: Ignacio Garrido-Laguna, MD         
United States, Vermont
University of Vermont Medical Center Recruiting
Burlington, Vermont, United States, 05401
Contact: Debbie McAdoo    802-656-9113   
Principal Investigator: Maura Barry, MD         
Sponsors and Collaborators
NewLink Genetics Corporation
Study Chair: Nicholas Vahanian, MD NewLink Genetics Corporation

Additional Information:
Responsible Party: NewLink Genetics Corporation Identifier: NCT02077881     History of Changes
Other Study ID Numbers: NLG2104
First Posted: March 4, 2014    Key Record Dates
Last Update Posted: June 20, 2017
Last Verified: June 2017

Keywords provided by NewLink Genetics Corporation:

Additional relevant MeSH terms:
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs