Clinical Trial testing TH-302 in combination with gemcitabine in combination in previously untreated patients with pancreatic cancer

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2012-002957-42-HU
• Date of registration: 06/05/2013
• Prospective Registration: Yes
• Primary sponsor: Threshold Pharmaceuticals
• Public title: Clinical Trial testing TH-302 in combination with gemcitabine in combination in previously untreated patients with pancreatic cancer
• Scientific title: A Randomized, Double-Blind, Phase III Study of the Efficacy and Safety of Gemcitabine in Combination With TH-302 Compared With Gemcitabine in Combination With Placebo in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
• Date of first enrolment: 27/06/2013
• Target sample size: 660
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002957-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: yes Other specify the comparator: Gemcitabine Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, Czech Republic, European Union, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Information
• Affiliation: Threshold Pharmaceuticals

• Name: Information
• Affiliation: Threshold Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion criteria:
- At least 18 years of age.
- Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven by
histology or cytology and previously untreated with chemotherapy or systemic therapy
- Measurable disease (at least one target lesion outside of previous radiation fields) or
non-measurable disease by RECIST 1.1 criteria (see Appendix III).
- Documentation of disease progression since any prior therapy.
- Life expectancy of at least 3 months.
- Acceptable liver function.
- Acceptable renal function.
- Acceptable hematologic status.
- Other protocol defined inclusion criteria may applied
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 260
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion criteria:
1. New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial
infarction within 6 months prior to the date of randomization, unstable arrhythmia or
symptomatic peripheral arterial vascular disease.
2. Symptomatic ischemic heart disease.
3. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at
least 3 months).
4. Previous malignancy other than pancreatic cancer in the last 5 years, except for adequately
treated non-melanoma skin cancer or pre-invasive cancer of the cervix.
5. Severe chronic obstructive or other pulmonary disease with hypoxemia
6. Major surgery, other than diagnostic surgery, =28 days prior to the date of randomization.
Subject must have completely recovered from surgery.
7. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
8. Treatment of pancreatic cancer with radiation therapy or surgery =28 days prior to the date of
randomization.
9. Prior therapy with a hypoxic cytotoxin.
10. Subjects who participated in an investigational drug or device trial =28 days prior to Day 1 of
the first cycle.
11. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
12. Subjects who have exhibited allergic reactions to a structural compound similar to TH-302 or
the drug product excipients or to gemcitabine or its excipients.
13. Other protocol defined exclusion criteria may applied.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Locally advanced unresectable pancreatic adenocarcinoma
MedDRA version: 19.0 Level: LLT Classification code 10033606 Term: Pancreatic cancer non-resectable System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: TH-302
Product Code: TH-302
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: not available
CAS Number: 918633-87-1
Current Sponsor code: TH-302
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: The primary objective of the trial is to evaluate efficacy, as measured by overall survival (OS), of gemcitabine in combination with TH-302 compared to gemcitabine in
combination with placebo in subjects with previously untreated locally advanced unresectable or metastatic pancreatic adenocarcinoma.

Primary end point(s): The primary endpoint is Overall Survival (OS) time.

Secondary Objective: To assess efficacy with resepct to:
? progression free survival (PFS), and
? objective response (OR) and disease control.
To assess patient reported outcomes (PROs) with respect to quality of life (QoL) measured with EORTC QLQ-C30 (Version 3) and EQ-5D-5L, and pain measured by a Numerical Rating Scale (NRS).
To investigate levels of carbohydrate antigen 19-9 (CA19-9),
To assess the safety and tolerability of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo.

Timepoint(s) of evaluation of this end point: OS will be evaluated when 508 events (deaths) of randomized patients are reported.

Secondary Outcome(s)

Secondary end point(s): - Progression-freee Survival (PFS) Time.
- Best Overall Respose Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Disease control Rate according to Response Evaluation Criteria in solid Tumors (RECIST) version 1.1.
- Quality of Life (QOL) EuroQuol-5D (EG-5D) Health Outcome questionnaire.
- Pain intensitiy using a visual analogue scale (VAS).
- Serum CA 19-9 response rate.
- Number of participants with treatment-emergent adverse events (TEAE) graded according to National Cancer Institute Common Terminology Criteria for Adverse Eents (NCI CTCAE v.4.03).

Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated at the same timepoint as OS data is mature.

Secondary ID(s)

EMR200592-001

2012-002957-42-BE

Source(s) of Monetary Support

Threshold Pharmaceuticals