Ovarian Cancer Metastatic Clinical Trial
— OVSTAROfficial 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
| Verified date | December 2020 |
| Source | Immetacyte Ltd |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | July 31, 2025 |
| Est. primary completion date | March 31, 2023 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - 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: 1. 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). 2. Expected to fulfil all entry criteria for OVSTAR Main Study 3. Written informed consent to Pre-Screening 4. Measurable disease by Response Evaluation Criteria in Solid Tumours 1.1 5. 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) 6. Medically suitable for a general anaesthetic and surgical biopsy (only applicable to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME) 7. Women of child bearing potential must be willing to practise a highly effective method of birth control once consented to pre-screening 8. World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3) 9. Age equal to or greater than 18 years 10. Life expectancy > 6 months 11. 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 12. Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis 13. Haematological and biochemical indices Exclusion Criteria: - Exclusion for Pre-Screening Phase Patients will not be invited to participate in Pre-Screening if any of the following criteria apply: 1. 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). 2. 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. 3. Evidence of any active significant infection. 4. Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT. 5. Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease). 6. 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. 7. 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. 8. Severe and active autoimmune disease. 9. On concomitant treatment with other experimental drugs within 4 weeks of TIL harvesting. 10. Patients not considered likely to comply with required follow up. 11. Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs. 12. Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells). 13. Patients who are pregnant or breast feeding should be excluded from pre-screening 14. Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded 15. Patents who have received live vaccines within 4 weeks prior to TIL therapy will be excluded Inclusion for Main Study -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: 1. 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). 2. Informed consent to Main Study 3. Confirmation from Sponsor of successful TIL growth 4. Measurable disease (by Response Evaluation Criteria in Solid Tumors 1.1) on CT within 4 weeks of main study entry 5. Left ventricular ejection fraction >50% on Echocardiogram scan 6. 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. 7. World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3) 8. Age equal to or greater than 18 years 9. Life expectancy > 6 months 10. 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 11. Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis 12. Haematological and biochemical indices Exclusion for Main Study 1. Patients receiving day 1 of their last cycle of chemotherapy or targeted therapy less than four weeks prior to pre-conditioning chemotherapy. 2. 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. 3. Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT. 4. Evidence of any active significant infection. 5. Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease). 6. 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. 7. 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. 8. Severe and active autoimmune disease. 9. 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. 10. Patients not considered likely to comply with required follow up. 11. Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs. 12. Patients who are pregnant or breast feeding should be excluded from entering the study 13. Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells). 14. 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. 15. Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded 16. Patents who have received live vaccines within 4 weeks prior to TIL therapy will be excluded. |
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Queens Elizabeth Hospital | Birmingham | |
| United Kingdom | The Christies Hospital | Manchester |
| Lead Sponsor | Collaborator |
|---|---|
| Immetacyte Ltd |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 6 weeks post treatment | |
| Primary | 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 | 12weeks post treatment | |
| Primary | 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 | up to 24 months post treatment | |
| Primary | Feasibility of treatment assessed by successful completion of planned treatment | Subjects will receive lymphodepletion followed by a single TIL treatment and supportive IL-2 | 5 days post TIL therapy | |
| Primary | Tolerability and safety assessed according to NCI CTCAE v5.0 grading. | Any adverse events related to study treatment will be recorded and assessed | up to 24 months post TIL therapy | |
| Secondary | 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 | up to 24 months post TIL therapy | |
| Secondary | Feasibility assessed by successful completion of planned treatment. | Subjects will receive lymphodepletion followed by a single TIL treatment and supportive IL-2 | 5 days post TIL therapy | |
| Secondary | 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 | up to 24 months post TIL therapy | |
| Secondary | Duration of overall response and stable disease | This is measured by time from response until radiological progression | up to 24 months post TIL therapy | |
| Secondary | Tolerability and safety assessed according to NCI CTCAE v5.0 grading | Any adverse events related to study treatment will be recorded and assessed | up to 24 months post TIL therapy | |
| Secondary | 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 | up to 24months post TIL therapy |