AzTrials
AzTrials

Melanoma and SarcomaPhase 1/2TITANNCT03555032

TITAN (Tumoural Injection of T-VEC and Isolated Limb Perfusion)

A Phase 1/2 study testing Talimogene laherparepvec (T-VEC) in people with Melanoma and Sarcoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will look at the safety and effects of combining a new drug called Talimogene Laherparepvec (T-VEC) with chemotherapy delivered by Isolated Limb Perfusion (ILP). The investigators want to find out whether these two treatments can be combined safely and whether T-VEC with ILP is better at treating your… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma and Sarcoma
What is being tested?
Talimogene laherparepvec (T-VEC)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited Kingdom
Study dates
26 Jun 2018to 1 Aug 2021
Phase
Phase 1/2
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
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males or females aged 18 years.
  • A confirmed histological diagnosis of in-transit malignant melanoma with or without regional lymph node metastases or limited visceral metastatic disease (AJCC Stage IIIb/c and IVa/b) or locally advanced soft-tissue sarcoma with or without regional or distant metastases (T2a/b, N0/1, M0/1) suitable for isolated limb perfusion.
  • Life expectancy of at least 3 months (as assessed, and documented by the Chief Investigator).
  • ECOG Performance Score of 0 to 2.
  • No continuing acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) Grade 1.
  • Completed any previous chemotherapy at least 28 days before entry into the study.
Show all 15Show fewer
  • Have baseline laboratory results as follows:
  • Absolute neutrophil count (ANC) 1.5 × 109 [SI units 109/L];
  • Platelets 100 ×109 [SI units 109/L] (without platelet transfusion);
  • Haemoglobin 9.0 g/dL [SI units gm/L] (with or without red blood cell (RBC) transfusion);
  • Serum creatinine 1.5 × upper limit of normal (ULN);
  • Bilirubin < 1.25 × ULN
  • ALT, AST and and alkaline phosphatase < 2 × ULN;
  • Calcium < 12 mg/dl (2.99 mmol/l).
  • Provide written informed consent in accordance with all applicable regulations and follow the study procedures. Patients must be capable

Who cannot join

  • Known cerebral metastases.
  • Have had concurrent immunotherapy during, and for the number of days equal to the half-life of that agent before or during, the study therapy.
  • Evidence of immunosuppression for any reason:
  • Known HIV disease
  • Acute or chronic hepatitis B or hepatitis C infection.
  • Chronic oral or systemic steroid medication use at a dose of > 10 mg/day of prednisolone or equivalent.
Show all 13Show fewer
  • Other signs or symptoms of clinical immune system suppression.
  • Open herpetic skin lesions.
  • A history of hypersensitivity to T-VEC or its excipients.
  • Pregnant or breast-feeding female. Confirmation that women of childbearing potential are not pregnant with a negative serum and urine beta-human chorionic gonadotrophin (beta-hCG) pregnancy test results must be obtained within 7 days prior to treatment initiation (i.e. the 1st administration of T-VEC).
  • Fertile males and females who are unwilling to employ highly effective means of contraception during study treatment and for 3 months after the last dose of study treatment.
  • Previous treatment with T-VEC for active disease.
  • Require intermittent or chronic treatment with an anti-herpetic drug (e.g. acyclovir), other than intermittent topical use.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • The Royal Marsden NHS Foundation Trust

    London, SW3 6JJ

Other trials in United Kingdom

About this study

Official title: A Phase I/II Study of the Safety and Efficacy of Talimogene Laherparepvec (T-VEC) Delivered by Intra-tumoural Injection in Combination With Isolated Limb Perfusion With Melphalan and Tumour Necrosis Factor-α in Patients With Advanced Extremity Tumours Including Metastatic Melanoma

This study will look at the safety and effects of combining a new drug called Talimogene Laherparepvec (T-VEC) with chemotherapy delivered by Isolated Limb Perfusion (ILP). The investigators want to find out whether these two treatments can be combined safely and whether T-VEC with ILP is better at treating your cancer than with ILP alone.

Read the detailed description

This is a non-randomised, single-centre Phase I/II study of the combination of the oncolytic virus, TVEC, administered by intra-tumoural (i.t.) injection in combination with isolated limb perfusion with melphalan and tumour necrosis factor in patients with advanced extremity tumours.

The safety of T-VEC administered by i.t. injection followed by isolated limb perfusion will be assessed in an initial safety run in comprised of six subjects as described below.

Cohort 1: The first subject will be recruited and will receive an initial dose of T-VEC 4-6 weeks prior to isolated limb perfusion.

A further preoperative dose of i.t. T-VEC will be given at 2-3 weeks prior to isolated limb perfusion.

A third dose will be given on the day of isolated limb perfusion. Following isolated limb perfusion, no further doses of TVEC shall be given. No further patients will be recruited until this patient has passed 30 days from the end of the study treatment. If this patient experiences a dose limiting toxicity (DLT), the Trial Steering Committee (TSC) will meet to consider termination of the study.

Cohort 2: Assuming no DLTs in Cohort 1, two further patients will be recruited and receive the study treatment as described above. Once these patients have passed 30 days from the end of the study treatment, the TSC will meet and perform a safety assessment.

Cohort 3: Assuming TSC approval following Cohort 2, three further patients will be recruited and receive the study treatment as described above. Once these patients have passed 30 days from the end of the study treatment, the TSC will meet and perform a safety assessment.

Cohort 4: Open recruitment up to a maximum of 15 patients in total, unless otherwise indicated by the TSC.

If more than 1 DLT is observed at any point in the study, the Chief Investigator will notify the TSC and recruitment will be suspended until further notification from the TSC.

Being tested
Talimogene laherparepvec (T-VEC)
Medical subject headings
Melanoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Talimogene laherparepvec (T-VEC)Drug

    One dose of 1 x 106 PFU/mL. Two doses of 1 x 108 PFU/mL. Given by intra-tumoural (i.t.) injection.

Study groups in NCT03555032
Study groupRoleWhat they receive
All patientsExperimentalAll patients will receive two pre-operative doses of T-VEC administered by intratumoural injection prior to a 3rd intratumoural dose given at the time of Isolated Limb Perfusion (ILP). No further treatment will be given.
Receives: Drug: Talimogene laherparepvec (T-VEC)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of dose limiting toxicities and adverse events when T-VEC administered by intratumoural injection is combined with Isolated Limb Perfusion [Safety and Tolerability]

    This will be assessed by serial blood tests and physical examinations from the first administration of T-VEC to 52 weeks follow-up

    Measured: From first T-Vec administration to 52 week follow up.

  2. The percentage of patients achieving complete/partial response following treatment [Efficacy]

    This will be assessed by serial physical examinations and/or imaging from 4 weeks following therapy until 52 weeks follow-up

    Measured: From T-Vec and ILP administration until 52 weeks follow up.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2018
  2. Study start26 Jun 2018
  3. Primary completion1 Aug 2021
  4. Study completion1 Aug 2021

Resources

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
Model description
Four Cohorts of patients staggered. Cohort 1: The first patient will need to be 30 days from the end of study treatment before patients can be consented to Cohort 2. Cohort 2: Assuming no Dose Limiting Toxicities in Cohort 1, two further patients will be recruited. Once these patients have passed 30 days from the end of study treatment Cohort 3 will open. Cohort 3: Three further patients will be recruited and be 30 days post before Cohort 4 opens. Cohort 4: Open recruitment for the remaining 9 patients.
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03555032
Sponsor's protocol ID
CCR 4679
Acronym
TITAN
Status last verified
Mar 2021
First submitted
9 May 2018
Last updated
18 Aug 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tulokas SKA, Kohtamaki LM, Makela SP, Juteau S, Alback A, Vikatmaa PJ, Mattila KE, Skytta TK, Koivunen JP, Tyynela-Korhonen K, Hernberg MM. Isolated limb perfusion with melphalan as treatment for regionally advanced melanoma of the limbs: results of 60 patients treated in Finland during 2007-2018. Melanoma Res. 2021 Oct 1;31(5):456-463. doi: 10.1097/CMR.0000000000000755.

    PubMed 34132224

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Talimogene laherparepvec (T-VEC) in people with Melanoma and Sarcoma, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.

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 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 18 Aug 2021. 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 Kingdom. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The number of dose limiting toxicities and adverse events when T-VEC administered by intratumoural injection is combined with Isolated Limb Perfusion [Safety and Tolerability] (time frame: From first T-Vec administration to 52 week follow up.). 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 NCT03555032, 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 18 Aug 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in