Clinical trial NCT02077881: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Pancreatic Adenocarcinoma
Metastatic Pancreatic Cancer
Keywords: metastatic
metastasis
Pancreatic
Pancreas
Cancer
adenocarcinoma
Lead sponsor: Lumos Pharma
Sponsor class: INDUSTRY
First posted: 2014-03-04
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Phase 2 Dosing
timeFrame: 10 months
measure: Regimen Limiting Toxicity
timeFrame: 10 months
measure: Overall Survival
timeFrame: 22 months
Secondary outcomes:
measure: Biomarker Response
timeFrame: 22 months
measure: Response Rate
timeFrame: 22 months
measure: Time to Progression of Disease
timeFrame: 22 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Lexington
country: United States
facility: University of Kentucy
state: Kentucky
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Paramus
country: United States
facility: The Vally Hospital
state: New Jersey
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health Systems
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Cancer Center and Research Institute
state: South Carolina
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
Study officials:
References: