Metastatic or Locally Advanced Unresectable Pancreatic AdenocarcinomaPhase 3MAESTRONCT01746979
Clinical Trial Testing TH-302 in Combination With Gemcitabine in Previously Untreated Subjects With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
A Phase 3 study testing TH-302 and Gemcitabine in people with Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma, run by ImmunoGenesis at 2 sites in 2 countries.
Trial summary
This Phase 3 trial is a randomized, double-blind, placebo-controlled trial of gemcitabine in combination with TH-302 compared to gemcitabine in combination with placebo in subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma
- What is being tested?
- TH-302 and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 693 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2012to May 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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
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- Measurable disease (at least one target lesion outside of previous radiation fields) or non-measurable disease by RECIST v.1.1 criteria
- Documentation of disease progression since any prior therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least 3 month
- Acceptable liver, renal function and acceptable hematological status
- Other protocol defined inclusion criteria may apply
Who cannot join
- 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
- Symptomatic ischemic heart disease
- Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
- 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
- Severe chronic obstructive or other pulmonary disease with hypoxemia
- Major surgery, other than diagnostic surgery, less than or equal to 28 days prior to the date of randomization. Subject must have completely recovered from surgery
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- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Treatment of pancreatic cancer with radiation therapy or surgery less than or equal to 28 days prior to the date of randomization
- Prior therapy with a hypoxic cytotoxin
- Subjects who participated in an investigational drug or device trial less than or equal to 28 days prior to Day 1 of the first cycle
- Known infection with Human Immunodeficiency Virus (HIV), or an active infection with Hepatitis B or Hepatitis C
- 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
- Other protocol defined exclusion criteria may apply
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Please Contact U.S. Medical Information
Rockland, Massachusetts
About this study
Official 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
This Phase 3 trial is a randomized, double-blind, placebo-controlled trial of gemcitabine in combination with TH-302 compared to gemcitabine in combination with placebo in subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma. Randomized subjects will receive TH-302 plus gemcitabine or gemcitabine plus placebo in 4-week cycles until there is evidence of progressive disease, intolerable toxicity, or the subject discontinues from the trial for other reasons (for example, withdrawal of consent). The primary efficacy endpoint is overall survival (OS) time. The data cut-off for statistical analyses of the primary and secondary endpoints will be reached when 508 events (deaths) will be reported. No planned interim analyses will be conducted. An Independent Safety Monitoring Board (ISMB) will provide periodic evaluations of the unblinded safety data to ensure subject safety and the validity and scientific merit of the study. A total of 660 subjects will be enrolled.
- Being tested
- TH-302, Gemcitabine, Placebo (5 percent dextrose - D5W)
- Keywords
- TH-302, Evofosfamide, Pancreatic Cancer, EMR200592-001
- Medical subject headings
- Neoplasm Metastasis, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-302Drug
TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
GemcitabineDrug
Gemcitabine will be administered at a dose of 1000 (mg/m^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
Placebo (5 percent dextrose - D5W)Drug
TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine plus TH-302 | Active comparator | Not described Receives: Drug: TH-302; Drug: Gemcitabine |
| Gemcitabine plus placebo | Placebo comparator | Not described Receives: Drug: Gemcitabine; Drug: Placebo (5 percent dextrose - D5W) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Overall survival is defined as time from randomization to death or last day known to be alive.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Secondary outcomes (1)
Progression Free Survival
Progression Free Survival is defined as the time from randomization to either first observation of progressive disease or occurrence of death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionFeb 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic or Locally Advanced Unresectable Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 693 participants (actual)
Sponsor and investigators
- Lead sponsor
- ImmunoGenesis
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Threshold Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Antonio Gualberto, MD, PhD, Study director, EMD Serono Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01746979
- Sponsor's protocol ID
- EMR 200592-001
- Other IDs
- 2012-002957-42
- Acronym
- MAESTRO
- Status last verified
- Oct 2017
- First submitted
- 7 Dec 2012
- Last updated
- 11 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Borad MJ, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, Schelman WR, Stephenson J Jr, Chiorean EG, Rosen PJ, Ulrich B, Dragovich T, Del Prete SA, Rarick M, Eng C, Kroll S, Ryan DP. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol. 2015 May 1;33(13):1475-81. doi: 10.1200/JCO.2014.55.7504. Epub 2014 Dec 15.
PubMed 25512461
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01746979
- Acronym / sponsor ID
- MAESTRO / EMR 200592-001
- Keywords
- TH-302, Evofosfamide, Pancreatic Cancer, EMR200592-001
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 693 participants (actual)
- Lead sponsor
- ImmunoGenesisIndustry (pharma, biotech, devices)
- Collaborators
- Threshold Pharmaceuticals
- Study start
- Dec 2012
- Primary completion
- Feb 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 11 Dec 2012 (estimated)
- Results
- Posted 2 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 3 trial is a randomized, double-blind, placebo-controlled trial of gemcitabine in combination with TH-302 compared to gemcitabine in combination with placebo in subjects with locally advanced unresectable or metastatic pancreatic adenocarcinoma. Randomized subjects will receive TH-302 plus gemcitabine or gemcitabine plus placebo in 4-week cycles until there is evidence of progressive disease, intolerable toxicity, or the subject discontinues from the trial for other reasons (for example, withdrawal of consent). The primary efficacy endpoint is overall survival (OS) time. The data cut-off for statistical analyses of the primary and secondary endpoints will be reached when 508 events (deaths) will be reported. No planned interim analyses will be conducted. An Independent Safety Monitoring Board (ISMB) will provide periodic evaluations of the unblinded safety data to ensure subject safety and the validity and scientific merit of the study. A total of 660 subjects will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine plus TH-302 | Active comparator | Drug: TH-302, Drug: Gemcitabine |
| Gemcitabine plus placebo | Placebo comparator | Drug: Gemcitabine, Drug: Placebo (5 percent dextrose - D5W) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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 other than:
- Measurable disease (at least one target lesion outside of previous radiation fields) or non-measurable disease by RECIST v.1.1 criteria
- Documentation of disease progression since any prior therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (13 listed)
- 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
- Symptomatic ischemic heart disease
- Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 3 months)
- 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
- Severe chronic obstructive or other pulmonary disease with hypoxemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TH-302TH-302 will be administered at a dose of 340 milligrams per square meter (mg/m^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal. | Drug | Gemcitabine plus TH-302 |
| GemcitabineGemcitabine will be administered at a dose of 1000 (mg/m^2) as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal. | Drug | Gemcitabine plus TH-302, Gemcitabine plus placebo |
| Placebo (5 percent dextrose - D5W)TH-302 placebo (5 percent dextrose - D5W) will be administered as intravenous infusion over 30 minutes on Day 1, 8 and 15 of every 28-day cycle. Doses will be administered until evidence of progressive disease, intolerable toxicity or subject withdrawal. | Drug | Gemcitabine plus placebo |
Primary outcome
Overall Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Overall survival is defined as time from randomization to death or last day known to be alive.
1 secondary outcome
Progression Free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25512461Borad MJ, Reddy SG, Bahary N, Uronis HE, Sigal D, Cohn AL, Schelman WR, Stephenson J Jr, Chiorean EG, Rosen PJ, Ulrich B, Dragovich T, Del Prete SA, Rarick M, Eng C, Kroll S, Ryan DP. Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol. 2015 May 1;33(13):1475-81. doi: 10.1200/JCO.2014.55.7504. Epub 2014 Dec 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Gualberto, MD, PhD study director
EMD Serono Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TH-302 and Gemcitabine in people with Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma, run by ImmunoGenesis at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01746979, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2025.