Metastatic Ovarian CancerPhase 1/2NCT03287674
TIL Therapy in Combination With Checkpoint Inhibitors for Metastatic Ovarian Cancer
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and TIL infusion in people with Metastatic Ovarian Cancer, run by Inge Marie Svane at 1 site in Denmark.
Trial summary
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Ovarian Cancer
- What is being tested?
- Cyclophosphamide, Fludarabine and TIL infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteDenmark
- Study dates
- 9 Oct 2017to 1 Jun 2020
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological proven advanced ovarian-, fallopian tube or primary peritoneal cancer with the possibility of surgical removal of tumor tissue of > 1 cm3.
- Progressive or recurrent resistant disease after platin-based chemotherapy (platinum resistant) or progressive or recurrent disease after second line or additional chemotherapy.
- Age: 18 - 70 years.
- ECOG performance status of ≤1 (Appendix 2).
- Life expectancy of > 6 months.
- At least one measurable parameter in accordance with RECIST 1.1 -criteria's.
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- No significant toxicities or side effects from previous treatments, except sensoric- and motoric neuropathy and/or alopecia
- Sufficient renal, hepatic and hematological function
- Men and women in the fertile age must use effective contraception. This applies from inclusion and until 6 months after treatment.
- Able to comprehend the information given and willing to sign informed consent
Who cannot join
- Other malignancies, unless followed for ≥ 5 years with no sign of disease
- Known hypersensitivity to one of the active drugs or one or more of the excipients.
- Severe medical or psychiatric conditions
- Creatinine clearance < 70 ml/min. In selected cases it can be decided to include a patient with a GFR < 70 ml/min with the use of a reduced dose of chemotherapy.
- Acute/chronic infection with HIV, hepatitis, syphilis among others.
- Severe allergies or previous anaphylactic reactions.
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- Active autoimmune disease
- Pregnant women and women breastfeeding.
- Need for immunosuppressive treatment e.g. corticosteroids or methotrexate. In selected cases a systemic dose of ≤10 mg prednisolone or a transient planned treatment that can be stopped before TIL therapy can be tolerated.
- Simultaneous treatment with other experimental drugs.
- Simultaneous treatment with other systemic anti-cancer treatments.
- Patients with active and uncontrollable hypercalcaemia.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Cancer Immune Therapy Dept. of Hematology/oncology
Copenhagen, 2730
About this study
Official title: T-cell Therapy in Combination With Checkpoint Inhibitors for Patients With Advanced Ovarian-, Fallopian Tube- and Primary Peritoneal Cancer
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.
Read the detailed description
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with ACT with TILs in combination with checkpoint inhibitors.
To evaluate treatment related immune responses To evaluate clinical efficacy
Design:
Patients will be screened with a physical exam, medical history, blood samples and ECG.
Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2 patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase the activity of the infused TIL product.
On day 0 patients receive TIL infusion and shortly after starts IL-2 stimulation with a daily subcutaneous dose for a total of 14 days.The patients will followed until progression or up to 5 years.
- Conditions
- Metastatic Ovarian Cancer
- Being tested
- Cyclophosphamide, Fludarabine, TIL infusion, Interleukin-2, Ipilimumab
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
FludarabineDrug
Also called Fludarabine phosphate
Fludarabine 25 mg/m2 is administered on day -5 to day -1.
TIL infusionBiological
Also called TILs
The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
Interleukin-2Drug
Also called IL-2
Interleukin-2 is administered as a daily low-dose subcutaneous injection of 2 MIU for a total of 14 days.
IpilimumabDrug
One dose of Ipilimumab 3 mg/kg is administered 14 days prior to surgical removal of tumor tissue for TIL expansion.
NivolumabDrug
Nivolumab 3 mg/kg is administered on day -2 before TIL infusion and every 2 weeks for a total of 4 doses.
| Study group | Role | What they receive |
|---|---|---|
| Patient group | Experimental | All patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks.
The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13.
Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2; Drug: Ipilimumab; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Reported Adverse Events by Type
Determine the safety of TIL therapy in combination with checkpoint inhibitors for patients with ovarian-, fallopian tube or primary peritoneal cancer by reporting adverse events according to CTCAE v. 4.0.
Measured: Up to 12 months
Secondary outcomes (4)
Treatment Related Immune Responses
Ex vivo anti-tumor reactivity of expanded TILs after co-culture measured with flow cytometry.
Measured: Until protocol end, until 6 months after TIL infusion
Objective Response Rate
Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CAT scan:
Complete Response (CR) Disappearance of all target lesions (sum of all taget lesions=0) Partial Response (PR) >=30% decrease (vs baseline) of sum of all target lesions dimension Progressive Disease (PD) new lesions or >=20% increase (vs smallest sum of target lesions or nadir) Stable Disease (SD) when sum of all target lesions does not qualify for CR/PR/PD
Measured: Assessed up to 12 months after therapy.
Overall Survival
Overall Survival (OS), defined as time from TIL infusion to death
Measured: Up to 3 years after TIL infusion
Progression Free Survival
Progression free survival (PFS): Time from TIL infusion to disease progression, relapse or death due to any cause, which ever comes first, will be used as an event.
Measured: Up to 12 months after TIL infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2017
- Study start9 Oct 2017
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
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.
- Other trials for Metastatic Ovarian CancerStudies 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inge Marie Svane
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Inge Marie Svane, Herlev Hospital
- Investigators
- Inge Marie Svane, Prof., M.D., Study director, Center for Cancer Immune Therapy, Depth of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730Magnus Pedersen, M.D., Principal investigator, Center for Cancer Immune Therapy, Depth of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03287674
- Sponsor's protocol ID
- GY1721
- Status last verified
- Feb 2023
- First submitted
- 14 Sep 2017
- Last updated
- 1 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T-cell Therapy in Combination With Checkpoint Inhibitors for Patients With Advanced Ovarian-, Fallopian Tube- and Primary Peritoneal Cancer
- ClinicalTrials.gov ID
- NCT03287674
- Acronym / sponsor ID
- GY1721
- Conditions
- Metastatic Ovarian Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Inge Marie SvaneUniversity, hospital or other
- Study start
- 9 Oct 2017 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 19 Sep 2017 (actual)
- Results
- Posted 22 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.
Detailed description
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. Recently, the investigators have completed a pilot study treating 6 patients with metastatic ovarian cancer. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 is administered to support T cell activation and proliferation in vivo.
The investigators recent pilot study has shown TIL therapy in patients with metastatic ovarian cancer to be feasible and tolerable. Mainly transient clinical responses where observed and therefore the investigators plan to combine TIL therapy with checkpoint inhibitors to potentially increase the clinical effect.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic ovarian cancer with ACT with TILs in combination with checkpoint inhibitors.
To evaluate treatment related immune responses To evaluate clinical efficacy
Design:
Patients will be screened with a physical exam, medical history, blood samples and ECG.
Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2 patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase the activity of the infused TIL product.
On day 0 patients receive TIL infusion and shortly after starts IL-2 stimulation with a daily subcutaneous dose for a total of 14 days.The patients will followed until progression or up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patient group | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: TIL infusion, Drug: Interleukin-2, Drug: Ipilimumab, Drug: NivolumabAll patients receive the same treatment. All patients are treated with one dose of Ipilimumab 14 days prior to surgical removal of tumor tissue for TIL expansion. Hospitalization for TIL treatment is approximately 3 weeks. The patients are admitted to hospital on day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine= on day -7 to day -1. The first of 4 doses of Nivolumab is administered on day -2 and every 2 weeks for at total of 4 doses. The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 13. Interleukin-2 is administered as a daily low-dose subcutaneous injection for a total for 14 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histological proven advanced ovarian-, fallopian tube or primary peritoneal cancer with the possibility of surgical removal of tumor tissue of > 1 cm3.
- Progressive or recurrent resistant disease after platin-based chemotherapy (platinum resistant) or progressive or recurrent disease after second line or additional chemotherapy.
- Age: 18 - 70 years.
- ECOG performance status of ≤1 (Appendix 2).
- Life expectancy of > 6 months.
Key exclusion criteria (12 listed)
- Other malignancies, unless followed for ≥ 5 years with no sign of disease
- Known hypersensitivity to one of the active drugs or one or more of the excipients.
- Severe medical or psychiatric conditions
- Creatinine clearance < 70 ml/min. In selected cases it can be decided to include a patient with a GFR < 70 ml/min with the use of a reduced dose of chemotherapy.
- Acute/chronic infection with HIV, hepatitis, syphilis among others.
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 |
|---|---|---|
| CyclophosphamideCyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. | Drug | Patient group |
| FludarabineAlso: Fludarabine phosphateFludarabine 25 mg/m2 is administered on day -5 to day -1. | Drug | Patient group |
| TIL infusionAlso: TILsThe maximum number of expanded TILs are infused over 30-45 minutes on day 0. | Biological | Patient group |
| Interleukin-2Also: IL-2Interleukin-2 is administered as a daily low-dose subcutaneous injection of 2 MIU for a total of 14 days. | Drug | Patient group |
| IpilimumabOne dose of Ipilimumab 3 mg/kg is administered 14 days prior to surgical removal of tumor tissue for TIL expansion. | Drug | Patient group |
| NivolumabNivolumab 3 mg/kg is administered on day -2 before TIL infusion and every 2 weeks for a total of 4 doses. | Drug | Patient group |
Primary outcome
Number of Participants With Reported Adverse Events by Type
Time frame: Up to 12 months
Determine the safety of TIL therapy in combination with checkpoint inhibitors for patients with ovarian-, fallopian tube or primary peritoneal cancer by reporting adverse events according to CTCAE v. 4.0.
4 secondary outcomes
Treatment Related Immune Responses
Time frame: Until protocol end, until 6 months after TIL infusion
Objective Response Rate
Time frame: Assessed up to 12 months after therapy.
Overall Survival
Time frame: Up to 3 years after TIL infusion
Progression Free Survival
Time frame: Up to 12 months after TIL infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Inge Marie Svane, Prof., M.D. study director
Center for Cancer Immune Therapy, Depth of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
Magnus Pedersen, M.D. principal investigator
Center for Cancer Immune Therapy, Depth of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730
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 Cyclophosphamide, Fludarabine and TIL infusion in people with Metastatic Ovarian Cancer, run by Inge Marie Svane at 1 site in Denmark.
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 10 inclusion and 12 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 1 Mar 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 Denmark. 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 22 Mar 2021). 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?
Number of Participants With Reported Adverse Events by Type (time frame: Up to 12 months). 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 1 Mar 2023.