Metastatic Renal Cell CarcinomaPhase 1NCT02926053
TIL Therapy for Metastatic Renal Cell Carcinoma
A Phase 1 study testing Surgical removal of tumor tissue for T cell production, Cyclophosphamide and Fludarabine in people with Metastatic Renal Cell Carcinoma, 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. The TILs are isolated from patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Renal Cell Carcinoma
- What is being tested?
- Surgical removal of tumor tissue for T cell production, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteDenmark
- Study dates
- Dec 2016to 31 Oct 2021
- Phase
- Phase 1
- 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 mRCC with the possibility of surgical removal of tumor tissue of > 1 cm3. Histology must include a clear cell component with or without a sarcomatoid dedifferentiation.
- Metastatic disease irrespective of number of previous treatment lines. Treatment naïve pt's can be included.
- ECOG performance status of ≤1.
- IMDC prognostic group 'Favorable' or 'Intermediary'.
- Life expectancy of > 6 months.
- At least one measurable parameter after surgery in accordance with RECIST 1.1 -criteria's.
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- No significant toxicities or side effects (CTC ≤ 1) from previous treatments.
- Normal ejection fraction (EF) measured by a multigated acquisition (MUGA) scan.
- Crom EDTA clearance >40 ml/min.
- Adequate renal, hepatic and hematological function.
- LDH ≤ 5 times upper normal limit as a measure of tumor burden.
- Women in the fertile age must use effective contraception. Likewise, men included in the study, as well as their partners, must use effective contraception. This applies from inclusion and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered safe contraceptives.
- Able to comprehend the information given and willing to sign informed consent.
- Willingness to participate in the planned controls.
Who cannot join
- A history of prior malignancies, except curatively treated non-melanoma skin cancer and CIS of the cervix uteri. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 3 years after treatment.
- Patients with cerebral metastases.
- Patients with widespread bone or bone only metastases.
- Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
- Severe medical conditions or psychiatric comorbidity.
- Acute/chronic infection with HIV, hepatitis, tuberculosis among others.
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- Severe and active autoimmune disease.
- Pregnant women and women breastfeeding.
- Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone, methotrexate among others).
- 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
Herlev, 2730
About this study
Official title: T Cell Therapy for Patients With Metastatic Renal Cell Carcinoma
Adoptive T cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. 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.
Recent studies suggest, that TIL therapy works in other cancers than Metastatic Melanoma, including Renal Cell Carcinoma. In this study TIL therapy is administered to patients with metastatic Renal Cell Carcinoma.
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. 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.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic renal cell carcinoma with ACT with TILs.
To evaluate treatment related immune responses . To evaluate clinical efficacy.
Design:
Patients will be screened with a physical exam, medical history, blood samples, pulmonary function test, Cr-EDTA clearance, MUGA scan and ECG.
Patients will undergo surgery to harvest tumor material for TIL production.
Patients is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7.
On day 0 patients receive TIL infusion and shortly after starts IL-2 administration with high-dose bolus IL-2 every eight hour for up to 5 days (maximum of 15 doses).
The patients will followed until progression or up to 5 years.
- Conditions
- Metastatic Renal Cell Carcinoma
- Being tested
- Surgical removal of tumor tissue for T cell production, Cyclophosphamide, Fludarabine, TIL infusion, Interleukin-2
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical removal of tumor tissue for T cell productionProcedure or surgery
Surgical removal of > 1 cm3 tumor tissue chosen with regards to high rate of success and to minimize the general risks involved in a surgical procedure.
CyclophosphamideDrug
Also called Cyclophospamide
Cyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6.
FludarabineDrug
Also called Fludarabinephosphate, Fludara
Fludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration.
TIL infusionBiological
Also called T Cell infusion
The maximum number of expanded TILs are infused over 30-45 minutes on day 0.
Interleukin-2Drug
Also called IL-2, Proleukin
Interleukin-2 is administered as high-dose bolus infusions (600.000 IU/kg) over a 15 minute period every 8 hours and continuing for up to 5 days (maximum of 15 doses).
| Study group | Role | What they receive |
|---|---|---|
| Patient group | Experimental | All patients receive the same treatment.
Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially.
All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses). Receives: Procedure: Surgical removal of tumor tissue for T cell production; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients in Which the Treatment Was Tolerable
Determine the safety of the administration of TIL therapy including lymphodepleting chemotherapy and Interleukin-2 for patients with metastatic renal cell cancer. This will be assessed clinically by whether the patients are able to receive treatment as described in the protocol.
Measured: 0-24 weeks
Secondary outcomes (2)
Number of Infusion Products With Detectable in Vitro Anti-tumor Responses
In vitro anti-tumor responses will be measured by cytokine production in a flow-cytometry based assed after co-culture of tumor-infiltrating lymphocytes from the infusion product with autologous tumor cells (from tumor digest and/or autologous tumor cell lines).
Measured: Up to 12 months
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2016 (estimated)
- Study startDec 2016
- Primary completion31 Oct 2021
- Study completion31 Oct 2021
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 Renal Cell CarcinomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 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 M Svane, Prof., MD, Study director, Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Borgmester Ib Juuls vej 25C, DK-2730Troels H Borch, MD, PhD, Principal investigator, Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Borgmester Ib Juuls vej 25C, DK-2730
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02926053
- Sponsor's protocol ID
- UG1617
- Status last verified
- Sep 2024
- First submitted
- 5 Oct 2016
- Last updated
- 22 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T Cell Therapy for Patients With Metastatic Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT02926053
- Acronym / sponsor ID
- UG1617
- Conditions
- Metastatic Renal Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Inge Marie SvaneUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- 31 Oct 2021 (actual)
- Study completion
- 31 Oct 2021 (actual)
- First posted
- 6 Oct 2016 (estimated)
- Results
- Posted 22 Nov 2024
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. 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.
Recent studies suggest, that TIL therapy works in other cancers than Metastatic Melanoma, including Renal Cell Carcinoma. In this study TIL therapy is administered to patients with metastatic Renal Cell Carcinoma.
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. 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.
Objectives:
To evaluate safety and feasibility when treating patients with metastatic renal cell carcinoma with ACT with TILs.
To evaluate treatment related immune responses . To evaluate clinical efficacy.
Design:
Patients will be screened with a physical exam, medical history, blood samples, pulmonary function test, Cr-EDTA clearance, MUGA scan and ECG.
Patients will undergo surgery to harvest tumor material for TIL production.
Patients is admitted day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7.
On day 0 patients receive TIL infusion and shortly after starts IL-2 administration with high-dose bolus IL-2 every eight hour for up to 5 days (maximum of 15 doses).
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 | Procedure: Surgical removal of tumor tissue for T cell production, Drug: Cyclophosphamide, Drug: Fludarabine, Biological: TIL infusion, Drug: Interleukin-2All patients receive the same treatment. Surgical removal of tumor tissue for T cell production, which takes 4-6 weeks, is performed initially. All patients are hospitalized during treatment (one week in advance of the T cell product being ready and for approximately 3 weeks in total) and receive treatment only once. The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine on day -7 to day -1. The TILs are infused on day 0 and Interleukin-2 therapy is administered on day 0 to day 5. Interleukin-2 is administered as high-dose i.v. bolus every eight hour starting approximately 6 hours after TIL infusion and for up to 5 days (maximum of 15 doses). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histological proven mRCC with the possibility of surgical removal of tumor tissue of > 1 cm3. Histology must include a clear cell component with or without a sarcomatoid dedifferentiation.
- Metastatic disease irrespective of number of previous treatment lines. Treatment naïve pt's can be included.
- ECOG performance status of ≤1.
- IMDC prognostic group 'Favorable' or 'Intermediary'.
- Life expectancy of > 6 months.
Key exclusion criteria (12 listed)
- A history of prior malignancies, except curatively treated non-melanoma skin cancer and CIS of the cervix uteri. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 3 years after treatment.
- Patients with cerebral metastases.
- Patients with widespread bone or bone only metastases.
- Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
- Severe medical conditions or psychiatric comorbidity.
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 |
|---|---|---|
| Surgical removal of tumor tissue for T cell productionSurgical removal of > 1 cm3 tumor tissue chosen with regards to high rate of success and to minimize the general risks involved in a surgical procedure. | Procedure or surgery | Patient group |
| CyclophosphamideAlso: CyclophospamideCyclophosphamide 60 mg/kg is administered i.v. on day -7 and day -6. | Drug | Patient group |
| FludarabineAlso: Fludarabinephosphate, FludaraFludarabine 25 mg/m2 is administered on day -5 to day -1. Maximum dose of 50 mg per administration. | Drug | Patient group |
| TIL infusionAlso: T Cell infusionThe maximum number of expanded TILs are infused over 30-45 minutes on day 0. | Biological | Patient group |
| Interleukin-2Also: IL-2, ProleukinInterleukin-2 is administered as high-dose bolus infusions (600.000 IU/kg) over a 15 minute period every 8 hours and continuing for up to 5 days (maximum of 15 doses). | Drug | Patient group |
Primary outcome
Number of Patients in Which the Treatment Was Tolerable
Time frame: 0-24 weeks
Determine the safety of the administration of TIL therapy including lymphodepleting chemotherapy and Interleukin-2 for patients with metastatic renal cell cancer. This will be assessed clinically by whether the patients are able to receive treatment as described in the protocol.
2 secondary outcomes
Number of Infusion Products With Detectable in Vitro Anti-tumor Responses
Time frame: Up to 12 months
Objective Response Rate
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
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Active, not recruitingPhase 3
Immunotherapy With Nivolumab and Ipilimumab Followed by Nivolumab or Nivolumab With Cabozantinib for Patients With Advanced Kidney Cancer, The PDIGREE Study
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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 M Svane, Prof., MD study director
Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Borgmester Ib Juuls vej 25C, DK-2730
Troels H Borch, MD, PhD principal investigator
Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital, Borgmester Ib Juuls vej 25C, 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 study testing Surgical removal of tumor tissue for T cell production, Cyclophosphamide and Fludarabine in people with Metastatic Renal Cell Carcinoma, 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 14 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 22 Nov 2024. 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 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.
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 Nov 2024). 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 Patients in Which the Treatment Was Tolerable (time frame: 0-24 weeks). 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 22 Nov 2024.