Non-small Cell Lung CancerPhase 2NCT02093962
Study of TH-302 or Placebo in Combination With Pemetrexed in Patients With Non-squamous Non-small Cell Lung Cancer
A Phase 2 study testing TH-302 combination with pemetrexed in people with Non-small Cell Lung Cancer, run by ImmunoGenesis at 80 sites in 10 countries.
Trial summary
The purpose of this study is to determine whether TH-302 in combination with pemetrexed is safe and effective in the treatment of non-squamous non-small cell lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- TH-302 combination with pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 265 participants
- Where
- 80 sitesin 10 countries
- Study dates
- Jun 2014to May 2016
- Phase
- Phase 2
- 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
- Men and women ≥ 18 years of age.
- Histologically or cytologically confirmed stage IIIB or IV NSCLC with non-squamous histology
- Recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance
- Neoadjuvant/adjuvant cytotoxic chemotherapy initiated < 12 months prior to study randomization will be counted as one prior treatment
- Neoadjuvant/adjuvant cytotoxic chemotherapy initiated ≥ 12 months prior to study randomization will not be counted as one prior chemotherapy treatment
- Use of targeted agents (e.g., monoclonal antibodies or kinase inhibitors) will not be counted as a prior chemotherapy treatment
Show all 12Show fewer
- Patients with known EGFR-activating mutations or ALK rearrangements should have received treatment with a targeted kinase inhibitor (e.g., erlotinib, crizotinib) and no longer be considered as a candidate for such treatment
- Measurable disease according to RECIST 1.1
- ECOG performance status 0-1
- Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior therapy
- Adequate hematologic, hepatic, cardiac, and renal function
- Female patients of childbearing potential must have a negative serum or urine pregnancy test, whichever is considered standard by the institution
Who cannot join
- Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or NSCLC NOS
- Prior therapy with pemetrexed
- Inability or unwillingness to take folic acid, vitamin B12 supplementation or corticosteroids
- Inability to discontinue non-steroidal anti-inflammatory drugs for 5 days (long half-life) or for 2 days (short half-life, if CrCL <80 mL/min) before pemetrexed dosing and until 2 days after pemetrexed dosing
- Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the following criteria are met:
- brain metastases are stable and have been previously treated with either whole-brain radiotherapy or gamma-knife surgery
Show all 19Show fewer
- steroids are currently not required and more than 14 days since last steroid treatment
- Symptomatic pleural effusion (> CTCAE Grade 1 dyspnea) that is not amenable to drainage
- Treatment with other systemic anticancer therapy within 4 weeks prior to the first dose of study medication
- Treatment with full field radiation therapy within 4 weeks or limited field radiation therapy within 2 weeks prior to the first dose of study medication
- Major surgery within 4 weeks or minor surgery within 2 weeks prior the first dose of study medication
- Elective or a planned major surgery while on study treatment
- Radiation therapy to greater than 25% of the bone marrow
- Clinically significant active infection (e.g. tuberculosis, viral hepatitis, HIV)
- Any other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct
- Concurrent active malignancy other than adequately treated basal cell or squamous cell carcinoma of the skin or pre-invasive carcinoma of the cervix.
- Pregnant or breast feeding
- Patients who are taking medications that prolong QT interval and have a risk of Torsades de Pointes (Appendix F) or who have a history of long QT syndrome
- Patients who are taking medications that are strong inducers or inhibitors of CYP3A4
Trial locations and contacts
80 sites in 10 countries.
80 sites in 10 countries
United States29 sites
St. Joseph Mercy Ann Arbor Cancer Center
Ann Arbor, Michigan, 48106
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889
UAB Cancer Center
Birmingham, Alabama, 35294
Gabrail Cancer Center Research
Canton, Ohio, 44718
Ironwood Cancer and Research Centers
Chandler, Arizona, 85224
Associates in Oncology & Hematology
Chattanooga, Tennessee, 37421
DORN VA Medical Center
Columbia, South Carolina, 29209
VA Eastern Colorado Healthcare System
Denver, Colorado, 80220
Durham VA Medical Center
Durham, North Carolina, 27705
California Cancer Center
Encinitas, California, 92024
Fpr Belvoir Community Hospital
Fort Belvoir, Virginia, 22060
San Antonio Military Medical Center
Fort Sam Houston, Texas, 78234
California Cancer Center Associates
Fresno, California, 93720
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Oncology Consultants
Houston, Texas, 77024
Millennium Oncology
Houston, Texas, 77090
Cancer Specialists of North Florida - CBO
Jacksonville Beach, Florida, 32256
Research Medical Center
Kansas City, Kansas, 64132
UCLA-Department of Medicine a Division of Hem/Onc
Los Angeles, California, 90095
AMPM Research
Miami, Florida, 33133
Ochsner Clinical Foundation
New Orleans, Louisiana, 70121
Clinical Research Alliance
New York, New York, 10021
Christiana Care Health Services
Newark, Delaware, 19713
Regional Cancer Care Institute at Regional Health
Rapid City, South Dakota, 57701
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
W.G. (Bill) Hefner VA Medical Center
Salisbury, North Carolina, 28144
Sarcoma Oncology Research Center
Santa Monica, California, 90403
Virginia Mason Medical Center
Seattle, Washington, 98101
Montefire-Einstein Center for Cancer Care
The Bronx, New York, 10461
Italy10 sites
Hospital Bellaria "Carlo Alberto Pizzardi" - Operative Unit of Oncology
Bologna, 40139
IRCCS Azienda Ospedallera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro
Genova
European Institute of Oncology (IEO) - Medical Care Unit
Milan, 20141
S. Gerardo Hospital - Complex Structure of Medical Oncology
Monza, 20900
Azienda Ospedaliera Universitaria Policlinico della Seconda Universita di Napoli
Naples
A.O.U.S. Luigi GonzagaUniversity Hospital
Orbassano, Torino, 10043
University Hospital of Pisa, Department of Cardothoracic Surgery, Operative unit of Pneumology
Pisa, 56124
"Santa Maria degli Angeli" - Hospital - Complex Operative Unit of Oncology
Pordenone, 33170
San Camillo-Forlanini Hospital - U.O.C. Pneumologia Oncologica 1
Rome, 00152
"Mater Salutis" Hospital - Operative Unit of Oncology
Verona, Legnago, 37045
Germany8 sites
Charité Universitätsmedizin Berlin;
Berlin, 12200
Klinikum Frankfurt Höchst GmbH
Frankfurt, 65929
Asklepios Fachkliniken Munchen-Gaunting
Gauting, Bavaria, 82131
Lungen Clinic Grosshandsdorf GmbH
Großhansdorf, 22927
Marien Hospital Herne
Herne, North Rhine-Westphalia
Universitatsklinikum Schleswig-Holstein
Lübeck, 23538
Städtisches Klinikum München - Klinikum Bogenhausen
München, 81925
Universitätsklinikum Ulm; Zentrum für Innere Medizin
Ulm, 89081
Russia7 sites
Republican Clinical Oncology Center under the Ministry of Healthcare of Tatarstan Republic
Kazan', Tatarstan Republic, 420029
Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of Medical Sciences
Moscow, 115478
Blokhin Russian Oncology Research Center
Moscow, 15478
State Healthcare Institution: Nizhny Novgorod Regional Oncology Center
Nizhny Novgorod, 603081
St. Petersburg Clinical Center for Applied Special Medical Services (Oncology)
Saint Petersburg, 194044
St. Petersburg 1st State Medical University n.a.I.P. Pavlov under the Ministry of Healthcare of the Russian Federation
Saint Petersburg, 197101
City Clinical Oncology Center, Oncology Department (Thoracic Oncology)
Saint Petersburg, 198255
Hungary6 sites
Koranyi National Institute of TBC and Pulmonology, 14th Dept of Pulmonology
Budapest, 1121
Koranyi National Institute of TBC and Pulmonology, 6th Department of Pulmonology
Budapest, 1121
Koranyi National Institute of TBC and Pulmonology, 8th Department of Pulmonology
Budapest, 1121
University of Debrecen, Medical and Health Science Center, Department of Pulmonology
Debrecen, 4032
Csongrad County Hospital of Chest Diseases
Deszk, 6772
Hetenyi Geza Hospital, Department of Oncology
Szolnok, 5004
Spain6 sites
General University Hospital Gregorio Maranon, Dept. of Oncology
Madrid, 28007
Jimenez Diaz Foundation
Madrid, 28040
Hospital Universitario Puerta de Hierro
Madrid, 28222
University Hospital Virgen de Valme
Seville, 41014
Dr. Peset University Hospital, Dept. of Oncology
Valencia, 46017
Hospital Universitario La Fe, Servicio de Oncologia
Valencia, 46026
Czechia4 sites
Hospital Na Bulovce, Department of Pneumology and Thoracic Surgery
Libeň, 18081
General Univesity Hospital in Prague, Clinic of Oncology
Prague, 12800
Thomayer Hospital, Clinic of Pneumology
Prague, 140 59
Regional Hospital T. Bta, Department of Pneumology
Zlín, 76275
Greece4 sites
IASO General, Oncology Unit
Athens, 15562
Attikon University General Hospital
Athens
Department of Medical Oncology
Heraklion, 71110
University General Hospital of Patras, Oncology Unit
Pátrai, 26500
Poland3 sites
Med-Polonia Sp. z o.o.
Poznan, 60693
L. Rydygier Provencial Hospitals in Torun, Dept. of Tumors Chemotherapy
Torun, 87-100
Maria Sklodowska-Curie Institute of Oncology in Warsaw
Warsaw, 02781
Romania3 sites
Pro. Dr. Alex Trestioreanu Institute of Oncology
Bucharest, 022328
Prof. Dr. Ioan Chiricuta Institute of Oncology
Cluj-Napoca, 400015
Oncology Centre "Sf. Nectarie"
Craiova, Dolj
About this study
Official title: A Randomized Phase 2, Double-blind, Placebo-controlled, Multi-center Study Comparing Pemetrexed in Combination With TH-302 vs. Pemetrexed in Combination With Placebo as Second-line Chemotherapy for Advanced Non-Squamous, Non-Small Cell Lung Cancer
The purpose of this study is to determine whether TH-302 in combination with pemetrexed is safe and effective in the treatment of non-squamous non-small cell lung cancer.
Read the detailed description
TH-302 is designed to target the hypoxic regions of tumors which are generally located distant from tumor vessels. Pemetrexed has poor tissue penetration and targets the regions of tumors that are located in proximity to the tumor vessels. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively target the hypoxic microenvironment. There is evidence supporting the presence of hypoxia in NSCLC lesions based on a hypoxia PET study. Combining pemetrexed with TH-302 may enable the targeting of both the normoxic and hypoxic regions of NSCLC lesions.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- TH-302 combination with pemetrexed, Matched placebo in combination with pemetrexed
- Keywords
- TH-302, TH-CR-415, Pemetrexed, Non-small cell lung cancer, Lung cancer, Evofosfamide
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-302 combination with pemetrexedDrug
400 mg/m2 of TH-302 will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle.
Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after TH-302 administration.
Matched placebo in combination with pemetrexedDrug
Matched placebo will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle.
Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after placebo administration.
| Study group | Role | What they receive |
|---|---|---|
| TH-302 and pemetrexed | Experimental | TH-302 in combination with pemetrexed Receives: Drug: TH-302 combination with pemetrexed |
| Placebo and pemetrexed | Active comparator | Matching placebo in combination with pemetrexed Receives: Drug: Matched placebo in combination with pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
To assess the efficacy of pemetrexed in combination with TH-302 as determined by overall survival in patients with advanced non-squamous NSCLC in the second-line chemotherapy setting compared with pemetrexed in combination with placebo
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2014 (estimated)
- Study startJun 2014
- Primary completionApr 2016
- Study completionMay 2016
Why it stopped: At the interim analysis, the futility boundary was not met and the study was stopped due to insufficient efficacy.
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.
- Other trials for Non-small Cell Lung CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 265 participants (actual)
Sponsor and investigators
- Lead sponsor
- ImmunoGenesis
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- EMD Serono
- Responsible party
- Sponsor
- Investigators
- Tillman Pearce, MD, Study chair, Threshold PharmaceuticalsJonathan Goldman, MD, Principal investigator, UCLA-Dept of Medicine a Div of Hem/Onc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02093962
- Sponsor's protocol ID
- TH-CR-415
- Status last verified
- May 2025
- First submitted
- 18 Mar 2014
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase 2, Double-blind, Placebo-controlled, Multi-center Study Comparing Pemetrexed in Combination With TH-302 vs. Pemetrexed in Combination With Placebo as Second-line Chemotherapy for Advanced Non-Squamous, Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02093962
- Acronym / sponsor ID
- TH-CR-415
- Conditions
- Non-small Cell Lung Cancer
- Keywords
- TH-302, TH-CR-415, Pemetrexed, Non-small cell lung cancer, Lung cancer, Evofosfamide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: At the interim analysis, the futility boundary was not met and the study was stopped due to insufficient efficacy.
- Enrolment
- 265 participants (actual)
- Lead sponsor
- ImmunoGenesisIndustry (pharma, biotech, devices)
- Collaborators
- EMD Serono
- Study start
- Jun 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 21 Mar 2014 (estimated)
- Results
- Posted 11 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether TH-302 in combination with pemetrexed is safe and effective in the treatment of non-squamous non-small cell lung cancer.
Detailed description
TH-302 is designed to target the hypoxic regions of tumors which are generally located distant from tumor vessels. Pemetrexed has poor tissue penetration and targets the regions of tumors that are located in proximity to the tumor vessels. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively target the hypoxic microenvironment. There is evidence supporting the presence of hypoxia in NSCLC lesions based on a hypoxia PET study. Combining pemetrexed with TH-302 may enable the targeting of both the normoxic and hypoxic regions of NSCLC lesions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TH-302 and pemetrexed | Experimental | Drug: TH-302 combination with pemetrexedTH-302 in combination with pemetrexed |
| Placebo and pemetrexed | Active comparator | Drug: Matched placebo in combination with pemetrexedMatching placebo in combination with pemetrexed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Men and women ≥ 18 years of age.
- Histologically or cytologically confirmed stage IIIB or IV NSCLC with non-squamous histology
- Recurrent or progressive disease after one prior platinum-based non-pemetrexed chemotherapy treatment for advanced disease with or without maintenance
- Neoadjuvant/adjuvant cytotoxic chemotherapy initiated < 12 months prior to study randomization will be counted as one prior treatment
- Neoadjuvant/adjuvant cytotoxic chemotherapy initiated ≥ 12 months prior to study randomization will not be counted as one prior chemotherapy treatment
Key exclusion criteria (19 listed)
- Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung or NSCLC NOS
- Prior therapy with pemetrexed
- Inability or unwillingness to take folic acid, vitamin B12 supplementation or corticosteroids
- Inability to discontinue non-steroidal anti-inflammatory drugs for 5 days (long half-life) or for 2 days (short half-life, if CrCL <80 mL/min) before pemetrexed dosing and until 2 days after pemetrexed dosing
- Leptomeningeal disease or any untreated or symptomatic brain metastases, unless the following criteria are met:
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-302 combination with pemetrexed400 mg/m2 of TH-302 will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle. Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after TH-302 administration. | Drug | TH-302 and pemetrexed |
| Matched placebo in combination with pemetrexedMatched placebo will be administered by IV infusion over 30 - 60 minutes on Day 1 and Day 8 of a 21-day cycle. Pemetrexed (500 mg/m2) will be administered as an IV infusion on Day 1 two - four hours after placebo administration. | Drug | Placebo and pemetrexed |
Primary outcome
Overall Survival
Time frame: 2 years
To assess the efficacy of pemetrexed in combination with TH-302 as determined by overall survival in patients with advanced non-squamous NSCLC in the second-line chemotherapy setting compared with pemetrexed in combination with placebo
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Tillman Pearce, MD study chair
Threshold Pharmaceuticals
Jonathan Goldman, MD principal investigator
UCLA-Dept of Medicine a Div of Hem/Onc
80 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TH-302 combination with pemetrexed in people with Non-small Cell Lung Cancer, run by ImmunoGenesis at 80 sites in 10 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 19 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: stopped early, as of the sponsor's last update on 16 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 80 sites in United States, Italy, Germany, Russia, Hungary and 5 more countries. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 11 Aug 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: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 May 2025.