Phase 2
N=7
TIL Therapy in Combination With Checkpoint Inhibitors for Metastatic Ovarian Cancer
Metastatic Ovarian Cancer
Bottom Line
View on ClinicalTrials.gov: NCT03287674 ↗Enrolled (actual)
7
Serious AEs
100.0%
Results posted
Mar 2021
Primary outcome: Primary: Number of Participants With Reported Adverse Events by Type — 3; 3; 1; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cyclophosphamide (Drug); Fludarabine (Drug); TIL infusion (Biological); Interleukin-2 (Drug); Ipilimumab (Drug); Nivolumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Inge Marie Svane
- Primary completion
- Jun 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Reported Adverse Events by Type |
3; 3; 1; 1; 1; 3 | — |
| SECONDARY Treatment Related Immune Responses |
6 | — |
| SECONDARY Objective Response Rate |
0; 1; 5; 0 | — |
| SECONDARY Overall Survival |
247 | — |
| SECONDARY Progression Free Survival |
93 | — |
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. 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.
Eligibility Criteria
Only patients within the Danish healthcare system are eligible for enrollment.
Inclusion Criteria
- 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.
- 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
Exclusion Criteria
- 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.
- 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.
Data sourced from ClinicalTrials.gov (NCT03287674). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.