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Ovarian Cancer MetastaticPhase 1/2OVSTARNCT04389229

OVSTAR TIL Trial (OVarian Cancer Co-STimulatory Antigen Receptor TIL Trial)

A Phase 1/2 study testing cyclophosphamide, fludarabine and IL-2 (Proleukin) in people with Ovarian Cancer Metastatic, run by Immetacyte Ltd at 2 sites in United Kingdom.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

An open label, multi-centre Phase 1/2a study of modified and unmodified autologous Tumour Infiltrating Lymphocytes (TIL) in patients with platinum-resistant ovarian cancer. The purpose of this phase I/II study is to evaluate the feasibility and safety of both standard unmodified TIL (UTIL-01) and TIL engineered to… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer Metastatic
What is being tested?
cyclophosphamide, fludarabine and IL-2 (Proleukin)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited Kingdom
Study dates
1 Jul 2020to 31 Jul 2025
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Criteria for Pre-Screening Phase
  • Patients are eligible to be included in the pre-screening phase of the study only if all of the following criteria apply:
  • Women with histologically confirmed recurrent metastatic platinum-resistant high-grade serous ovarian cancer (HGSOC) (platinum resistant defined as progressing within 6 months of last platinum-containing combination chemotherapy. Patients must have received at least 1 line of prior platinum-containing combination chemotherapy and have completed at least 4 cycles of this treatment).
  • Expected to fulfil all entry criteria for OVSTAR Main Study
  • Written informed consent to Pre-Screening
  • Measurable disease by Response Evaluation Criteria in Solid Tumours 1.1
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  • Have disease suitable for fresh TIL harvesting from tumour biopsies (only applicable to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)
  • Medically suitable for a general anaesthetic and surgical biopsy (only applicable to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)
  • Women of child bearing potential must be willing to practise a highly effective method of birth control once consented to pre-screening
  • World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)
  • Age equal to or greater than 18 years
  • Life expectancy > 6 months
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the Pre-Screening or Main Study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis
  • Haematological and biochemical indices
  • -Patients are eligible to be included in the Main Study only if all of the following criteria, and the inclusion criteria listed in Section 1.3.1, apply:
  • Women with metastatic platinum resistant high-grade serous ovarian cancer (HGSOC) who have recurrent disease (platinum resistant defined as progressing within 6 months of last platinum-containing combination chemotherapy. patients must have received at least 1 line of prior platinum-containing combination chemotherapy and have completed at least 4 cycles of this treatment).
  • Informed consent to Main Study
  • Confirmation from Sponsor of successful TIL growth
  • Measurable disease (by Response Evaluation Criteria in Solid Tumors 1.1) on CT within 4 weeks of main study entry
  • Left ventricular ejection fraction >50% on Echocardiogram scan
  • Patients must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regime if appropriate.
  • World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)
  • Age equal to or greater than 18 years
  • Life expectancy > 6 months
  • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the Pre-Screening or Main Study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
  • Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis
  • Haematological and biochemical indices

Who cannot join

  • Patients will not be invited to participate in Pre-Screening if any of the following criteria apply:
  • History of a previous malignancy at another site, unless followed for >2 years with no sign of recurrent disease (local completely excised cutaneous basal cell, squamous cell carcinoma or in situ carcinoma will be allowed).
  • Patients receiving chemotherapy, targeted therapy, immunotherapy or systemic steroids including steroid doses >10mg/day of prednisolone (or equivalent) during the previous four weeks prior to TIL harvesting. Patients who require such therapies intermittently due to pre-existing disorders are also excluded.
  • Evidence of any active significant infection.
  • Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT.
  • Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease).
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  • Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or class III or IV American Heart Association criteria for heart disease.
  • Patients who are at high medical risk because of non-malignant systemic disease including those with uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which, in the lead clinician's opinion, would not make the patient a good candidate for adoptive TIL therapy.
  • Severe and active autoimmune disease.
  • On concomitant treatment with other experimental drugs within 4 weeks of TIL harvesting.
  • Patients not considered likely to comply with required follow up.
  • Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs.
  • Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells).
  • Patients who are pregnant or breast feeding should be excluded from pre-screening
  • Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded
  • Patents who have received live vaccines within 4 weeks prior to TIL therapy will be excluded
  • Patients receiving day 1 of their last cycle of chemotherapy or targeted therapy less than four weeks prior to pre-conditioning chemotherapy.
  • Patients receiving systemic immunosuppressive therapy including steroids at doses higher than 10mg/day of prednisolone (or equivalent) within four weeks of commencing pre-conditioning chemotherapy (unless this is required briefly as anti-emetic prophylaxis for the treatments detailed in above point 1). Patients who require such therapies intermittently due to pre-existing disorders are also excluded.
  • Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT.
  • Evidence of any active significant infection.
  • Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease).
  • Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or class III or IV American Heart Association criteria for heart disease.
  • Patients who are at high medical risk because of non-malignant systemic disease including those with uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which, in the lead clinician's opinion, would not make the patient a good candidate for adoptive TIL therapy.
  • Severe and active autoimmune disease.
  • Receiving concomitant treatment with any other experimental drugs within 4 weeks of pre-conditioning chemotherapy. Patients receiving experimental immunotherapies will be discussed with the sponsor.
  • Patients not considered likely to comply with required follow up.
  • Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs.
  • Patients who are pregnant or breast feeding should be excluded from entering the study
  • Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells).
  • Caution should be exercised for patients requiring regular drainage of ascites or pleural effusions. When there is sufficient fluid to be safely drained, drainage must be performed prior to trial enrolment and pre-conditioning chemotherapy in those patients.
  • Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded
  • Patents who have received live vaccines within 4 weeks prior to TIL therapy will be excluded.

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Queens Elizabeth Hospital

    Birmingham

  • The Christies Hospital

    Manchester

Other trials in United Kingdom

About this study

Official title: Protocol Title: An Open Label, Multi-centre Phase 1/2a Study of Modified and Unmodified Autologous Tumour Infiltrating Lymphocytes (TIL) in Patients With Platinum-resistant Ovarian Cancer

An open label, multi-centre Phase 1/2a study of modified and unmodified autologous Tumour Infiltrating Lymphocytes (TIL) in patients with platinum-resistant ovarian cancer. The purpose of this phase I/II study is to evaluate the feasibility and safety of both standard unmodified TIL (UTIL-01) and TIL engineered to express the co-stimulatory receptor CoStAR (CoTIL-01) in platinum resistant ovarian cancer.

Read the detailed description

This is a single-arm Phase 1/2a study of unmodified (UTIL-01) and gene modified (CoTIL-01) adoptive TIL therapy which will enrol sequentially. A total of 8 patients will be recruited to the UTIL-01 cohort to receive autologous standard unmodified TIL (phase 2). Up to 14 patients will receive autologous gene engineered TIL(CoTIL-1) in a dose escalation design (Phase 1/2a). Once patients have met all the pre-screening inclusion criteria, and that sponsor has confirmed a successful TIL harvest, a request to manufacture will be sent to the Sponsor to initiate TIL production. Manufacturing and quality control assessment is anticipated to take approximately 6 weeks. During this time, patients may receive standard of care chemotherapy (bridging chemotherapy) as deemed appropriate by the treating oncology team. Patients will proceed to the main trial after completion of bridging chemotherapy. Once the TIL product is certified for release, and that patient has consented to the main trial and has completed main trial screening assessments, study treatment can be scheduled.

Patients will receive non-myeloablative lymphodepleting pre-conditioning chemotherapy with cyclophosphamide 600mg/m2/day and fludarabine 30mg/m2/day on Day -5, -4 and -3. Chemotherapy will aim to be delivered as an outpatient, but patients can be admitted if clinically needed. Patients will be required to maintain oral hydration of >2 litres per day. If this is felt to be difficult to achieve then the patient will be admitted for IV fluids. Patients will be admitted for TIL infusion on Day 0. The TIL infusion will be administered at least 36 hours after last dose of chemotherapy. The cells will only be thawed once an Investigator has made a positive decision to go ahead with infusion and confirmed this in writing. TIL infusion may be delayed for up to 7 days for clinical reasons or for issues regarding the cell specification. This decision must be made before final preparation for infusion. Following TIL infusion, patients will commence subcutaneous interleukin-2 at a fixed dose of 18 million units once a day. Patients must remain an inpatient for the duration of IL-2 treatment for a minimum of 7 days post TIL infusion. Recruitment to the study will occur over approximately 24-month period. Recruitment to CoTIL-01 will commence after UTIL-01. Patients will be followed up in the study for 24 months post TIL infusion.

Being tested
cyclophosphamide, fludarabine, IL-2 (Proleukin), Unmodified Tumour Infiltrating Lymphocytes (UTIL-01), Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01)

What participants receive

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

  • cyclophosphamideDrug

    600mg/m2/day for 3 days ( on day -5, -4, -3)

  • fludarabineDrug

    30mg/m2/day for 3 days ( on day -5, -4, -3)

  • IL-2 (Proleukin)Drug

    Subcutaneous injections at a fixed dose of 18 million units once a day following TIL infusion

  • Unmodified Tumour Infiltrating Lymphocytes (UTIL-01)Genetic

    Also called TIL

    Single dose at 5 x 10^9 - 5 x 10^10

  • Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01)Genetic

    Also called engineeredTIL

    Single dose at 2 x10^9 (+/- 20%) (engineered TIL)

Study groups in NCT04389229
Study groupRoleWhat they receive
UTIL-01ExperimentalSingle dose autologous unmodified tumour infiltrating lymphocytes
Receives: Drug: cyclophosphamide; Drug: fludarabine; Drug: IL-2 (Proleukin); Genetic: Unmodified Tumour Infiltrating Lymphocytes (UTIL-01)
CoTIL-01ExperimentalSingle dose autologous gene modified tumour infiltrating lymphocytes
Receives: Drug: cyclophosphamide; Drug: fludarabine; Drug: IL-2 (Proleukin); Genetic: Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01)

What is being measured

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

  1. Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

    Subjects will have CT scan at 6 weeks post treatment to compare with baseline CT scans in order to assess disease response to therapy

    Measured: 6 weeks post treatment

  2. Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

    Subjects will have CT scan at 12 weeks post treatment to compare with baseline and previous post treatment CT scans in order to assess disease response to therapy

    Measured: 12weeks post treatment

  3. Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

    Subjects will have CT scan every 12 weeks after week 12 post treatment to compare with baseline and previous post treatment CT scans in order to assess disease response to therapy

    Measured: up to 24 months post treatment

  4. Feasibility of treatment assessed by successful completion of planned treatment

    Subjects will receive lymphodepletion followed by a single TIL treatment and supportive IL-2

    Measured: 5 days post TIL therapy

  5. Tolerability and safety assessed according to NCI CTCAE v5.0 grading.

    Any adverse events related to study treatment will be recorded and assessed

    Measured: up to 24 months post TIL therapy

Secondary outcomes (6)

  1. Percentage change in CA125 according to the Gynaecologic Cancer InterGroup CA125 response definition

    Serum level of CA125 will be measured in patients on day of discharge, 4weeks, 6weeks,12weeks and 3 monthly post TIL treatment

    Measured: up to 24 months post TIL therapy

  2. Feasibility assessed by successful completion of planned treatment.

    Subjects will receive lymphodepletion followed by a single TIL treatment and supportive IL-2

    Measured: 5 days post TIL therapy

  3. Progression free survival

    This will be measured by time from treatment initiation (from first day of pre-conditioning chemotherapy to radiological disease progression, relapse or death due to any cause

    Measured: up to 24 months post TIL therapy

  4. Duration of overall response and stable disease

    This is measured by time from response until radiological progression

    Measured: up to 24 months post TIL therapy

  5. Tolerability and safety assessed according to NCI CTCAE v5.0 grading

    Any adverse events related to study treatment will be recorded and assessed

    Measured: up to 24 months post TIL therapy

  6. Objective response by RECIST v1.1

    Subjects who have received CoTIL-01 will have CT scan at 6 weeks, 12 weeks, then very 12 weeks post treatment to compare with baseline and previous post treatment CT scans in order to assess disease response to therapy

    Measured: up to 24months post TIL therapy

Timeline

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

  1. First posted15 May 2020
  2. Study start1 Jul 2020 (estimated)
  3. Primary completion31 Mar 2023 (estimated)
  4. Study completion31 Jul 2025 (estimated)

Why it stopped: Sponsor decision

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
Non-randomised
Intervention model
Sequential
Model description
This study has two cohorts which will open sequentially. This is not a randomized controlled trial.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04389229
Sponsor's protocol ID
IMM-2019T-01-OC
Other IDs
2019-000106-30, 2019
Acronym
OVSTAR
Status last verified
Dec 2020
First submitted
22 Jan 2020
Last updated
16 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing cyclophosphamide, fludarabine and IL-2 (Proleukin) in people with Ovarian Cancer Metastatic, run by Immetacyte Ltd at 2 sites 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 28 inclusion and 32 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: withdrawn, as of the sponsor's last update on 16 Dec 2020. 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 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 was withdrawn before enrolling participants, so there are no results.

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?

Disease objective response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (time frame: 6 weeks post treatment). The study lists 5 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 NCT04389229.

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 Dec 2020.

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