Clinical trial NCT02047500: Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer
Official title: An Open-Label, Phase I Dose Escalation Trial of TH-302 in Combination With Gemcitabine and Nab-Paclitaxel in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: TH-302
Nab-paclitaxel
Gemcitabine
Evofosfamide
Lead sponsor: ImmunoGenesis
Sponsor class: INDUSTRY
Collaborators: name: Threshold Pharmaceuticals
First posted: 2014-01-28
Enrollment: 19
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 is a multicenter, open-label, Phase 1, dose escalation trial to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of TH-302 in combination with gemcitabine and nab-paclitaxel in previously untreated subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma.


Eligibility criteria: Inclusion Criteria:

* Subjects greater than or equal to (\>=) 18 years of age with locally advanced unresectable or metastatic pancreatic adenocarcinoma proven by histology or cytology and previously untreated with chemotherapy or systemic therapy other than:

  * Radiosensitizing doses of 5-fluorouracil;
  * Radiosensitizing doses of gemcitabine if relapse occurred at least 6 months after completion of gemcitabine;
  * Neoadjuvant chemotherapy if relapse occurred at least 6 months after surgical resection;
  * Adjuvant chemotherapy if relapse occurred at least 6 months after completion of adjuvant chemotherapy
* Subjects may have measurable or non-measurable disease according to RECIST 1.1.
* Eastern cooperative oncology group (ECOG) performance status of 0 or 1
* Acceptable hematological status, liver and renal function as defined in the protocol
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Significant cardiac or peripheral vascular arterial disease
* Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
* Severe chronic obstructive or other pulmonary disease with hypoxemia
* Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
* Subjects receiving concomitant treatment with radiotherapy or other investigational drugs
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Number of Subjects Experiencing Dose Limiting Toxicity (DLT)
timeFrame: Up to Day 28 of Cycle 1
Secondary outcomes:
measure: Progression Free Survival (PFS) Time
timeFrame: Time from enrollment to progressive disease (PD) or occurrence of death due to any cause within 120 days of either first administration of study drug or the last tumor assessment
measure: Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria
timeFrame: Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
measure: Duration of Overall Response According to RECIST Version 1.1 Criteria
timeFrame: Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
measure: Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria
timeFrame: Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment
measure: Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria
timeFrame: Baseline and 8 weeks after Day 1 of Cycle 1
measure: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 30 after the last dose of study treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Sun JD, Liu Q, Ahluwalia D, Li W, Meng F, Wang Y, Bhupathi D, Ruprell AS, Hart CP. Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer. Cancer Biol Ther. 2015;16(3):438-49. doi: 10.1080/15384047.2014.1003005.