Soft Tissue SarcomaPhase 1/2NCT02453191
TVEC and Preop Radiation for Sarcoma (4 ml Dose)
A Phase 1/2 study testing Talimogene Laherparepvec and Radiotherapy in people with Soft Tissue Sarcoma, run by University of Iowa at 1 site in United States.
Trial summary
The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy. Approximately 30 people will take part in this study conducted by investigators at the University of Iowa. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Talimogene Laherparepvec and Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2015to 10 Mar 2023
- Phase
- Phase 1/2
- 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
- Subject has provided informed consent.
- Histologically confirmed diagnosis of locally advanced STS that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate.
- EXAMPLES:
- Resectable stage IIB, III, and IV disease that are not suitable for surgically resection alone due to inability to achieve clear margins.
- Including metastatic (stage IV) disease for which radiotherapy and surgical resection are indicated.
- Except certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas.
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- Previous treatment: prior systemic anti-cancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy are allowed provided therapy completed at least 1 year prior to enrollment.
- No prior Talimogene laherparepvec or tumor vaccines allowed.
- No prior radiation to the same tumor bed allowed.
- Age ≥18 years.
- Both men and women of all races and ethnic groups are eligible for this trial.
- ECOG performance status ≤1.
- Patient must have measurable disease:
- Tumor size at least ≥ 5 cm in the longest diameter as measured by CT scan or MRI for which radiation is feasible.
- Patient must have injectable disease (direct injection or ultrasound guided).
Who cannot join
- Certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas.
- History or evidence of sarcoma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
- Subjects with retroperitoneal and visceral sarcoma.
- History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn's disease) or other symptomatic autoimmune disease including, inflammatory bowel disease, or history of any poorly controlled or severe systemic autoimmune disease (i.e., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, type I diabetes, or autoimmune vasculitis).
- History of other malignancy within the past 3 years except treated with curative intent and no known active disease present and has not received chemotherapy for ≥ 1 year before enrollment/randomization and low risk for recurrence.
- History of prior or current autoimmune disease.
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- History of prior or current splenectomy or splenic irradiation.
- Active herpetic skin lesions
- Require intermittent or chronic treatment with an anti-herpetic drug (e.g., acyclovir), other than intermittent topical use.
- Any non-oncology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period.
- Concomitant treatment with therapeutic anticoagulants such as warfarin.
- Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).
- Acute or chronic hepatitis B or hepatitis C infection (requires negative test for clinically suspected hepatitis B or hepatitis C infection).
- Evidence of hepatitis B -
- Positive HBV surface antigen (indicative for chronic hepatitis B or recent acute hepatitis B).
- Negative HBV surface antigen but positive HBV total core antibody (indicative for resolved hepatitis B infection or occult hepatitis B) and detectable copies of HBV DNA by PCR (detectable HBV DNA copies suggest occult hepatitis B).
- Evidence of hepatitis C -
- 1. Positive HCV antibody and positive HCV RNA by PCR (undetectable RNA copies suggest past and resolved hepatitis C infection).
- Female subjects who are pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment.
- Female subjects of childbearing potential or male subjects who are unwilling to use 2 highly effective methods of contraception during study treatment and through 3 months after the last dose of study treatment. See Section 7.5 for more details.
- Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s).
- Other investigational procedures while participating in this study that could affect the primary objective of the study as determined by the PI are excluded.
- Subject previously has entered this study.
- Patients who are receiving any other investigational agents.
- Evidence of CNS metastases.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to talimogene laherparepvec.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients on or requiring immunosuppressive therapies.
- Any of the following laboratory abnormalities:
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count (ANC) < 1500 per mm3
- Platelet count < 100,000 per mm3
- Total bilirubin > 1.5 × ULN
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × ULN
- Alkaline phosphatase > 2.5 × ULN
- PT (or INR) and PTT (or aPTT) > 1.5 × ULN
- Creatinine > 2.0 × ULN
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
Official title: Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas
The purpose of this research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy.
Approximately 30 people will take part in this study conducted by investigators at the University of Iowa.
Read the detailed description
This is a single-arm open-label phase Ib and phase II clinical study assessing the safety and relative efficacy of concurrent talimogene laherparepvec in combination with radiotherapy in patients with soft tissue sarcomas. Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care.
- Conditions
- Soft Tissue Sarcoma
- Being tested
- Talimogene Laherparepvec, Radiotherapy
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Talimogene LaherparepvecDrug
Talimogene Laherparepvec
RadiotherapyRadiation
Concurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Talimogene Laherparepvec in combination with radiotherapy
Talimogene Laherparepvec Dose Levels:
• Initial dose for all = talimogene laherparepvec up to 4.0 mL of 106 PFU/mL Receives: Drug: Talimogene Laherparepvec; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b: Number of Subjects With Dose Limiting Toxicities (DLTs)
A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.
Measured: 14 weeks
Phase 2: Pathologic Tumor Necrosis Rate
Pathologic tumor necrosis rate is defined as the percentage of subjects with pathologic tumor necrosis ≥ 95%.
Measured: 14 weeks
Secondary outcomes (4)
Overall Response Rate
Overall response rate is defined as the percentage of patients with a confirmed complete or partial response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT:
Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is a 30% decrease in the sum of the longest dimensions of the target lesions, relative to baseline. Progressive disease (PD) is an increase of 20% or more in the sum of the longest dimension of target lesions. Stable disease (SD) is a decrease in the tumor size of < 30% or an increase of < 20%.
Measured: 24 months
Percentage of Participants With 2 Year Progression-Free Survival
Progression-free survival is defined as the time from treatment initiation to the date of first documentation of disease progression or death due to any cause. Otherwise, patients are censored at the date of last radiographic assessment for progression.
Measured: 24 months
Percentage of Participants With 2 Year Overall Survival
Overall survival is defined as the time from treatment initiation to death due to any cause. Patients still alive are censored at last date known to be alive.
Measured: 24 months
Number of Participants With Adverse Events (AEs)
To further assess the safety of talimogene laherparepvec given concurrently with preoperative external beam radiation in sarcoma patients.Information regarding the occurrence of adverse events will be collected from the time the subject signs the informed consent form and throughout their participation in the study, including a period of 30 days after the last dose of study drug.
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2015 (estimated)
- Study start13 Jul 2015
- Primary completion22 Jan 2019
- Study completion10 Mar 2023
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 Soft Tissue SarcomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Mohammed Milhem, University of Iowa
- Investigators
- John Rieth, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02453191
- Sponsor's protocol ID
- 201504731 (4 milliliter dose)
- Status last verified
- Jun 2024
- First submitted
- 28 Apr 2015
- Last updated
- 20 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Monga V, Miller BJ, Tanas M, Boukhar S, Allen B, Anderson C, Stephens L, Hartwig S, Varga S, Houtman J, Wang L, Zhang W, Jaber O, Thomason J, Kuehn D, Rajput M, Metz C, Zamba KD, Mott S, Abanonu C, Bhatia S, Milhem M. Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial. J Immunother Cancer. 2021 Jul;9(7):e003119. doi: 10.1136/jitc-2021-003119.
PubMed 34330766
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Intralesional Injection of Talimogene Laherparepvec With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas
- ClinicalTrials.gov ID
- NCT02453191
- Acronym / sponsor ID
- 201504731 (4 milliliter dose)
- Conditions
- Soft Tissue Sarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 13 Jul 2015 (actual)
- Primary completion
- 22 Jan 2019 (actual)
- Study completion
- 10 Mar 2023 (actual)
- First posted
- 25 May 2015 (estimated)
- Results
- Posted 17 Jun 2020
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 research study is to determine the safety and tolerability of talimogene laherparepvec when combined with radiation therapy.
Approximately 30 people will take part in this study conducted by investigators at the University of Iowa.
Detailed description
This is a single-arm open-label phase Ib and phase II clinical study assessing the safety and relative efficacy of concurrent talimogene laherparepvec in combination with radiotherapy in patients with soft tissue sarcomas. Patients will be treated with neoadjuvant radiation and weekly intratumoral injections of talimogene laherparepvec. Weekly injections of talimogene laherparepvec will be continued until surgery. Surgery will be performed 4-6 weeks from the end of radiation therapy to allow for resolution of acute toxicities per current standard of care.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Talimogene Laherparepvec, Radiation: RadiotherapyTalimogene Laherparepvec in combination with radiotherapy Talimogene Laherparepvec Dose Levels: • Initial dose for all = talimogene laherparepvec up to 4.0 mL of 106 PFU/mL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subject has provided informed consent.
- Histologically confirmed diagnosis of locally advanced STS that is unresectable with clear wide margins, for which preoperative radiotherapy is considered appropriate.
- Resectable stage IIB, III, and IV disease that are not suitable for surgically resection alone due to inability to achieve clear margins.
- Including metastatic (stage IV) disease for which radiotherapy and surgical resection are indicated.
- Except certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas.
Key exclusion criteria (37 listed)
- Certain histologic subtypes: GIST, Desmoid, Ewing sarcoma, Kaposi sarcoma, and bone sarcomas.
- History or evidence of sarcoma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
- Subjects with retroperitoneal and visceral sarcoma.
- History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn's disease) or other symptomatic autoimmune disease including, inflammatory bowel disease, or history of any poorly controlled or severe systemic autoimmune disease (i.e., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, type I diabetes, or autoimmune vasculitis).
- History of other malignancy within the past 3 years except treated with curative intent and no known active disease present and has not received chemotherapy for ≥ 1 year before enrollment/randomization and low risk for recurrence.
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 |
|---|---|---|
| Talimogene LaherparepvecTalimogene Laherparepvec | Drug | Treatment |
| RadiotherapyConcurrent Preoperative Radiation. External Beam Radiation Therapy (EBRT) will be given at the standard dose for resectable soft tissue sarcomas. according to the NCCN sarcoma guidelines. | Radiation | Treatment |
Primary outcome
Phase 1b: Number of Subjects With Dose Limiting Toxicities (DLTs)
Time frame: 14 weeks
A DLT is defined as any of the following talimogene laherparepvec-related toxicity or related to the combination of talimogene laherparepvec and radiation therapy during treatment and up to 4 weeks after the last talimogene laherparepvec injection: Grade 3 or greater immune-mediated adverse events, Grade 3 or greater allergic reactions, any grade plasmacytoma, any other unexpected grade 3 or greater hematologic or non-hematologic toxicity, with the exceptions of: any grade of alopecia, expected radiation related skin toxicity of any grade, Grade 3 arthralgia or myalgia, brief (< 1 week) grade 3 fatigue, Grade 3 fever, Grade 3 diarrhea or vomiting responding to supportive case.
Phase 2: Pathologic Tumor Necrosis Rate
Time frame: 14 weeks
Pathologic tumor necrosis rate is defined as the percentage of subjects with pathologic tumor necrosis ≥ 95%.
4 secondary outcomes
Overall Response Rate
Time frame: 24 months
Percentage of Participants With 2 Year Progression-Free Survival
Time frame: 24 months
Percentage of Participants With 2 Year Overall Survival
Time frame: 24 months
Number of Participants With Adverse Events (AEs)
Time frame: 14 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34330766Monga V, Miller BJ, Tanas M, Boukhar S, Allen B, Anderson C, Stephens L, Hartwig S, Varga S, Houtman J, Wang L, Zhang W, Jaber O, Thomason J, Kuehn D, Rajput M, Metz C, Zamba KD, Mott S, Abanonu C, Bhatia S, Milhem M. Intratumoral talimogene laherparepvec injection with concurrent preoperative radiation in patients with locally advanced soft-tissue sarcoma of the trunk and extremities: phase IB/II trial. J Immunother Cancer. 2021 Jul;9(7):e003119. doi: 10.1136/jitc-2021-003119.
- Individual participant dataSharing planned: No
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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.
John Rieth, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Talimogene Laherparepvec and Radiotherapy in people with Soft Tissue Sarcoma, run by University of Iowa at 1 site in United States.
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 15 inclusion and 37 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 20 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 17 Jun 2020). 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?
Phase 1b: Number of Subjects With Dose Limiting Toxicities (DLTs) (time frame: 14 weeks). The study lists 2 primary outcomes in all. 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 NCT02453191, 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 20 Jun 2024.