MelanomaPhase 2NCT04427306
Neoadjuvant T-VEC in High Risk Early Melanoma
A Phase 2 study testing T-Vec in people with Melanoma, run by University of California, Davis at 1 site in United States.
Trial summary
Despite the recent notable advances in the treatment of advanced melanoma with application of growing immunotherapies, patterns of response and factors resulting in treatment failure are poorly understood. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Melanoma
- What is being tested?
- T-Vec
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 21 May 2020to 21 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ability to understand and willingness to sign an informed consent form.
- Ability to adhere to the study visit schedule and other protocol requirements.
- Men and women ≥18 years of age.
- ECOG performance status score of 0-1 (Appendix 13.1) / Karnofsky Performance Status (KPS) performance status of 60% or greater.
- Life expectancy ≥ 3 months.
- Hematology parameters defined by:
Show all 20Show fewer
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L,
- Platelet count ≥ 75 × 109/L, and
- Hemoglobin ≥ 8 g/dL (may have been transfused)
- Blood chemistry levels defined by:
- Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
- AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
- INR and aPTT ≤1.5 x ULN (for patients on anticoagulation they must be receiving a stable dose for at least 1 week prior to first treatment)
- Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula.
- Subjects with active hepatitis B virus (Hep B) and with untreated hepatitis C virus (HCV) are allowed.
- Willingness to undergo mandatory pre-treatment biopsy (unless there is adequate archival tumor specimen available) and mandatory on-treatment biopsy.
- Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Or, female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration.
- Male and female subjects who agree to use highly effective method of birth control (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices [IUDs], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug.
- Biopsy-proven resectable primary cutaneous melanoma > 2.0mm in depth with residual tumor or local, in-transit, or dermal oligometastatic resectable recurrence in a treatment- naïve patient not otherwise eligible for systemic therapy
- Residual pigmented cutaneous lesion accessible to intralesional injection
Who cannot join
- Pregnant or lactating women.
- Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- Any significant medical condition including additional malignancies, laboratory abnormalities, or psychiatric illness that would prevent the subject from participating and adhering to study related procedures.
- Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial.
- Severe infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 4 weeks prior to enrollment.
- Melanoma >/= 2.0mm in depth without residual disease following biopsy
Show all 28Show fewer
- Previous exposure to talimogene laherparepvec or systemic therapies
- Concurrent cancer or treatment for a concurrent cancer, except treated non-melanoma skin cancer
- Regional or systemic metastases
- History of evidence of symptomatic autoimmune disease requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Immunosuppressed state, including the following:
- Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease, concurrent opportunistic infection, receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid doses > 10 mg/day of prednisone or equivalent within 7 days prior to enrollment.
- Prior immunosuppressive, chemotherapy, radiotherapy (in which the field encompassed a planned injection site), biological cancer therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
- Active human immunodeficiency virus (HIV) infection
- Active herpetic skin lesions or prior complication of herpes simplex virus-1 infection (e.g., herpetic keratitis or encephalitis).
- Current enrollment in another clinical trial
- Patients who are know to be sensitive to any of the products or components of T-VEC
- Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical use.
- Previous treatment with talimogene laherparepvec or any other oncolytic virus.
- Prior therapy with tumor vaccine or received live vaccine within 28 days prior to enrollment.
- Adjuvant hormonal therapy is allowed if appropriate for planned study.
- Prior radiotherapy in which the field does not overlap the injection sites or non- immunosuppressive targeted therapy within 14 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 14 days prior to enrollment
- History of other malignancy within the past 5 years with the following exceptions:
- Adequately treated non melanoma skin cancer without evidence of disease at the time of enrollment
- Adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment
- Adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment
- Prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment.
- Subjects who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV-1 induced complications such as immunosuppressed individuals, individuals known to have HIV infection, pregnant women, or infants under the age of 3 months, during talimogene laherparepvec treatment and through 30 days after the last dose
Trial locations and contacts
1 site in 1 country.
United States1 site
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: Biomarker Analysis of Neoadjuvant Intralesional Therapy in High Risk Early Melanoma
Despite the recent notable advances in the treatment of advanced melanoma with application of growing immunotherapies, patterns of response and factors resulting in treatment failure are poorly understood. Moreover, the application of these therapeutics has been limited in the neoadjuvant setting, particularly in earlier stage disease, even though this strategy has improved tolerance and efficacy with other modalities of therapy in other cancer types.
Survival remains significantly poorer for thicker and ulcerated lesions with T3b and T4 lesions demonstrating less than 50% survival at 5 years independent of other prognostic indicators. Oncolytic viral therapies (OVT) stimulate or suppress the immune system in different ways to stop cancer cells from growing and intra-lesional OVT has demonstrated comparable efficacy and durability with greater tolerability than most effective systemic therapy. Talimogene laherparepvec (T-VEC) is the only phase III approved intra-lesional therapy in melanoma and has demonstrated significantly improved overall response rate (64%) and bystander effect (34% in uninjected lesions) in the therapeutic setting for advanced disease.
The investigators propose an open-label, Phase 2 study of talimogene laherparepvec (T-VEC), in the neoadjuvant setting for patients with high-risk, resectable primary and cutaneous melanoma prior to definitive excision. The central hypothesis of this proposal is that neoadjuvant intra-lesional therapy with T-VEC in high risk early stage melanoma will effectively treat local and subclinical distant disease by enhanced immune recognition, immunomodulation of the nodal basin, and still allow for standard of care surgery. The primary aim of this study will be to evaluate for histologic response of melanoma with secondary aim to determine changes in immune response and draining sentinel nodes as well as relationship of immune phenotype to response rate, stage and nodal burden. The investigators plan for thorough exploratory analysis of genetic and microenvironmental changes to identify actionable targets in incomplete as well as evaluation of changes in sentinel burden and subsequent rates of locoregional disease control, recurrence-free survival and overall survival in long term follow up. The investigators predict that histologic clearance of the primary tumor in the surgical specimen will be associated with improved RFS.
Read the detailed description
In summary, the goal of this project is to conduct a phase II study to evaluate efficacy of Talimogene laherparepvec in the neoadjuvant setting for primary invasive melanoma in effort to improve currently poor outcomes for these tumors. This strategy has not yet been explored in early phase disease despite dramatic results seen with neoadjuvant therapeutics in other cancer types and recent clinical studies demonstrating efficacy of this approach in advanced resectable melanoma. Our ability to predict non-responder from responder to immunotherapeutic agents such as T-VEC is not yet defined and the risk of universal exposure to these systemic agents may outweigh the hypothesized benefit given the potential for immune-mediated toxicity as well as associated costs. More importantly, mechanistic dissection of pathways and molecular/immunological signatures of response and resistance offer the promise of a more rational and targeted selection of immunotherapy to maximize benefits and minimize risks. This study would be first in kind to target high earlier stage melanoma in the neoadjuvant setting with a less toxic intra-tumoral immunotherapy with key correlative endpoints regarding immune mechanisms of response.
- Conditions
- Melanoma
- Being tested
- T-Vec
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-VecDrug
Also called talimogene laherparepvec, Amgen
(talimogene laherparepvec) will be given prior to surgery. Standard care the patients receive the drug after sugery
| Study group | Role | What they receive |
|---|---|---|
| Treatment (talimogene laherparepvec) | Experimental | This study all subject get the research treatment drug (talimogene laherparepvec) Receives: Drug: T-Vec |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic response
Clinical efficacy and biologic effect will be calculated by measuring rates of pathologic response based on assessment of immunologic response and molecular changes in residual tumors. Based on this assessment, patients will be assigned to one of the four categories described below:
Pathologic response defined as:
- Pathologic Complete Response (pCR, defined as 0% residual tumor)
- Major Pathologic Response (defined as ≤10% residual tumor)
- Partial Pathologic Response (pPR, defined as less than or equal to 50% viable tumor cells)
- Pathologic Non-Response (pNR, defined as greater than 50% viable tumor cells)
The analysis will be based on intent-to-treat (ITT). If a patient fails to complete treatment or disease reassessment, then he/she will be counted as a non-responder, even though the exact response is unknown.
Measured: At surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start21 May 2020
- Primary completion27 Jun 2022
- Study completion21 May 2024 (estimated)
Why it stopped: low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Cameron Gaskill, MD, Principal investigator, UC Davis Department of SurgeryMichael C Lowe, MD, Principal investigator, Emory University Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04427306
- Sponsor's protocol ID
- 1529612
- Other IDs
- UCDCCSO034
- Status last verified
- Sep 2023
- First submitted
- 7 Apr 2020
- Last updated
- 15 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Analysis of Neoadjuvant Intralesional Therapy in High Risk Early Melanoma
- ClinicalTrials.gov ID
- NCT04427306
- Acronym / sponsor ID
- 1529612
- Conditions
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: low enrollment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 21 May 2020 (actual)
- Primary completion
- 27 Jun 2022 (actual)
- Study completion
- 21 May 2024 (estimated)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite the recent notable advances in the treatment of advanced melanoma with application of growing immunotherapies, patterns of response and factors resulting in treatment failure are poorly understood. Moreover, the application of these therapeutics has been limited in the neoadjuvant setting, particularly in earlier stage disease, even though this strategy has improved tolerance and efficacy with other modalities of therapy in other cancer types.
Survival remains significantly poorer for thicker and ulcerated lesions with T3b and T4 lesions demonstrating less than 50% survival at 5 years independent of other prognostic indicators. Oncolytic viral therapies (OVT) stimulate or suppress the immune system in different ways to stop cancer cells from growing and intra-lesional OVT has demonstrated comparable efficacy and durability with greater tolerability than most effective systemic therapy. Talimogene laherparepvec (T-VEC) is the only phase III approved intra-lesional therapy in melanoma and has demonstrated significantly improved overall response rate (64%) and bystander effect (34% in uninjected lesions) in the therapeutic setting for advanced disease.
The investigators propose an open-label, Phase 2 study of talimogene laherparepvec (T-VEC), in the neoadjuvant setting for patients with high-risk, resectable primary and cutaneous melanoma prior to definitive excision. The central hypothesis of this proposal is that neoadjuvant intra-lesional therapy with T-VEC in high risk early stage melanoma will effectively treat local and subclinical distant disease by enhanced immune recognition, immunomodulation of the nodal basin, and still allow for standard of care surgery. The primary aim of this study will be to evaluate for histologic response of melanoma with secondary aim to determine changes in immune response and draining sentinel nodes as well as relationship of immune phenotype to response rate, stage and nodal burden. The investigators plan for thorough exploratory analysis of genetic and microenvironmental changes to identify actionable targets in incomplete as well as evaluation of changes in sentinel burden and subsequent rates of locoregional disease control, recurrence-free survival and overall survival in long term follow up. The investigators predict that histologic clearance of the primary tumor in the surgical specimen will be associated with improved RFS.
Detailed description
In summary, the goal of this project is to conduct a phase II study to evaluate efficacy of Talimogene laherparepvec in the neoadjuvant setting for primary invasive melanoma in effort to improve currently poor outcomes for these tumors. This strategy has not yet been explored in early phase disease despite dramatic results seen with neoadjuvant therapeutics in other cancer types and recent clinical studies demonstrating efficacy of this approach in advanced resectable melanoma. Our ability to predict non-responder from responder to immunotherapeutic agents such as T-VEC is not yet defined and the risk of universal exposure to these systemic agents may outweigh the hypothesized benefit given the potential for immune-mediated toxicity as well as associated costs. More importantly, mechanistic dissection of pathways and molecular/immunological signatures of response and resistance offer the promise of a more rational and targeted selection of immunotherapy to maximize benefits and minimize risks. This study would be first in kind to target high earlier stage melanoma in the neoadjuvant setting with a less toxic intra-tumoral immunotherapy with key correlative endpoints regarding immune mechanisms of response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (talimogene laherparepvec) | Experimental | Drug: T-VecThis study all subject get the research treatment drug (talimogene laherparepvec) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Ability to understand and willingness to sign an informed consent form.
- Ability to adhere to the study visit schedule and other protocol requirements.
- Men and women ≥18 years of age.
- ECOG performance status score of 0-1 (Appendix 13.1) / Karnofsky Performance Status (KPS) performance status of 60% or greater.
- Life expectancy ≥ 3 months.
Key exclusion criteria (28 listed)
- Pregnant or lactating women.
- Any psychiatric condition that would prohibit the understanding or rendering of informed consent.
- Any significant medical condition including additional malignancies, laboratory abnormalities, or psychiatric illness that would prevent the subject from participating and adhering to study related procedures.
- Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial.
- Severe infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 4 weeks prior to enrollment.
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 |
|---|---|---|
| T-VecAlso: talimogene laherparepvec, Amgen(talimogene laherparepvec) will be given prior to surgery. Standard care the patients receive the drug after sugery | Drug | Treatment (talimogene laherparepvec) |
Primary outcome
Pathologic response
Time frame: At surgery
Clinical efficacy and biologic effect will be calculated by measuring rates of pathologic response based on assessment of immunologic response and molecular changes in residual tumors. Based on this assessment, patients will be assigned to one of the four categories described below: Pathologic response defined as: * Pathologic Complete Response (pCR, defined as 0% residual tumor) * Major Pathologic Response (defined as ≤10% residual tumor) * Partial Pathologic Response (pPR, defined as less than or equal to 50% viable tumor cells) * Pathologic Non-Response (pNR, defined as greater than 50% viable tumor cells) The analysis will be based on intent-to-treat (ITT). If a patient fails to complete treatment or disease reassessment, then he/she will be counted as a non-responder, even though the exact response is unknown.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2023.
- Learn more or sign up for the study here!Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Melanoma
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
RecruitingPhase 1/2
Hepzato Kit and Opdualag for Metastatic Melanoma and Liver Metastasis
Metastatic Melanoma, Liver Metastases
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
RecruitingPhase 1
A Study of BI 3810944 in Patients With Advanced Cancer
Solid Tumours, Melanoma
Not yet recruitingPhase 1/2
Combination Immunotherapy Targeting Melanoma
Melanoma
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.
Cameron Gaskill, MD principal investigator
UC Davis Department of Surgery
Michael C Lowe, MD principal investigator
Emory University Winship Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing T-Vec in people with Melanoma, run by University of California, Davis 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 20 inclusion and 28 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: paused, as of the sponsor's last update on 15 Sep 2023. 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 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?
Results are not available in the source record.
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?
Pathologic response (time frame: At surgery). 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 15 Sep 2023.