Phase I TH-302 Plus Gemcitabine Plus Nab-Paclitaxel in Pancreatic Cancer

NCT02047500 | Terminated Phase 1 Results

• 1 other identifier: EMR200592-006
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

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.

Conditions

Pancreatic Cancer

Keywords

TH-302; Nab-paclitaxel; Gemcitabine; Evofosfamide

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Experiencing Dose Limiting Toxicity (DLT)

  Up to Day 28 of Cycle 1

Secondary Outcomes (6)

• Progression Free Survival (PFS) Time

  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

• Percentage of Subjects With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) Criteria

  Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment

• Duration of Overall Response According to RECIST Version 1.1 Criteria

  Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment

• Percentage of Subjects With Disease Control According to RECIST Version 1.1 Criteria

  Every 8 weeks from Day 1 of Cycle 1 until disease progression or within 1 week after discontinuation of study treatment

• Tumor Metabolic Response Assessed by Positron Emission Tomography (PET) Scans According to European Organization for Research and Treatment of Cancer (EORTC) Criteria

  Baseline and 8 weeks after Day 1 of Cycle 1

Study Arms (1)

TH-302 plus Nab-paclitaxel plus Gemcitabine

EXPERIMENTAL

Drug: TH-302; Drug: Nab-paclitaxel; Drug: Gemcitabine

Interventions

TH-302 DRUG

TH-302 will be administered at a dose ranging from 170-340 milligram per square meter (mg/m\^2) as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.

TH-302 plus Nab-paclitaxel plus Gemcitabine

Nab-paclitaxel DRUG

Nab-paclitaxel will be administered at a dose ranging from 100-125 mg/m\^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.

TH-302 plus Nab-paclitaxel plus Gemcitabine

Gemcitabine DRUG

Gemcitabine will be administered at a dose ranging from 800-1000 mg/m\^2 as intravenous infusion over 30 minutes on Days 1, 8 and 15 of every 28-day cycle until evidence of progressive disease, intolerable toxicity or subject withdrawal.

TH-302 plus Nab-paclitaxel plus Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ImmunoGenesis: lead
• Threshold Pharmaceuticals: collaborator

Study Sites (5)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (1)

• 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.

  PMID: 25679067 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

TH 302; 130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Thomas Wilson
• Organization: Threshold Pharmaceuticals

twilson@thresholdpharm.com

302-359-0565

Study Officials

• Medical Responsible

  EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: January 28, 2014
• Study Start: January 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: May 1, 2016
• Last Updated: May 11, 2025
• Results First Posted: December 15, 2017

Record last verified: 2025-05

Locations

US (5)