Metastatic Ovarian CancerPhase 2NCT03412526
Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian
A Phase 2 study testing Fludarabine, Radiation and TIL administration in people with Metastatic Ovarian Cancer, run by Sheba Medical Center at 1 site in Israel.
Trial summary
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2. Most TIL ACT trials have been conducted as salvage therapy for patients who already had failed numerous treatments; many study participants presented with multiple metastases… Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Metastatic Ovarian Cancer
- What is being tested?
- Fludarabine, Radiation and TIL administration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteIsrael
- Study dates
- 21 Jan 2018to 1 Feb 2022
- Phase
- Phase 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 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand and sign the Informed Consent Form.
- Pathology confirmed epithelial Ovarian/Fallopian Tube/Primary Peritoneal carcinomatosis.
- For ovarian/peritoneal carcinoma: Platinum- resistant or platinum refractory disease (platinum-resistant disease is defined as disease-progression within 6 months of completion of prior platinum containing regimen, whereas platinum refractory disease is defined as disease progression while on platinum containing regimen or within 3 months from first line, adjuvant chemotherapy).
- Received and exhausted standard of care therapies for recurrent ovarian cancer and further chemotherapy lines have no proven added value. (For platinum resistant disease, received no more than 3 prior chemotherapy lines, whereas for platinum refractory disease received no more than 2 previous chemotherapy lines).
- Patients must have at least one lesion that is resectable for TIL generation.
- Have measurable disease per RECIST 1.1.
Show all 32Show fewer
- Patients with one or more brain metastases less than 1 cm each, and any patients with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 6 weeks.
- Greater than or equal to 18 years of age.
- For Patients with child bearing potential, willing to practice birth control from the start of chemotherapy until 120 days after release from the hospital.
- Life expectancy of greater than three months
- Performance status of ECOG 0 or 1
- Adequate organ function defined by lab test results:
- Hematology:
- Absolute neutrophil count greater than 1000/mm3 without support of filgrastim Normal WBC greater than 3000/mm3. Hemoglobin greater than 9.0 g/dL Platelet count greater than 100,000/mm3
- Serology:
- Seronegative for HIV antibody. Seronegative for Hepatitis B or Hepatitis C (patients who recovered from previous infection and have no detected HBSAg or HCV RNA are allowed).
- Chemistry:
- Serum ALT/AST less than three times the upper limit of normal (ULN). Serum creatinine less than or equal to 1.6 mg/dL Total bilirubin no more than 1.5 times the ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 mg/dL.
- Negative pregnancy test in women of child bearing potential.
- More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients may have undergone minor surgical procedures with the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
- Note: As described in the Study Population section in the synopsis, before entering the trial, the medical team will present other available experimental therapies to the patient for her consideration.
- SUBJECT EXCLUSION CRITERIA
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the non-myeloablative, lymphodepleting induction regimen on the fetus or infant. (Note: Pregnancies occurring in patients with Ovarian cancer are very rare, but possible. For this reason, ELIM has decided to retain the sections dealing with possible cases of pregnancy during the study.)
- Systemic steroid therapy required (patients who require replacement therapy for adrenal insufficiency may be enrolled if steroid treatment dose do not exceed 10 mg of prednisone or equivalent).
- Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
- Opportunistic infections (the experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
- History of severe immediate hypersensitivity reaction to any of the agents used in this study , including history of an anaphylactic reaction to penicillin or gentamicin
- History of coronary revascularization or ischemic heart disease.
- Any patient known to have an LVEF less than or equal to 50 percent.
- Documented LVEF of less than or equal to 50 percent tested in patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
- Documented FEV1 and DLCO (relative to predicted) less than or equal to 60 percent.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Sheba medical Center
Ramat Gan, 5262100
Jacob Schachter, Prof., 972-3-5304907, jacob.scachter@sheba.health.gov.il
Meital Bar, 972-3-5305201, meital.bar@sheba.health.gov.il
About this study
Official title: A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2.
Most TIL ACT trials have been conducted as salvage therapy for patients who already had failed numerous treatments; many study participants presented with multiple metastases, frequently in visceral organs and even in the brain. The effectiveness of TIL ACT in eradicating metastatic tumors of the responding patients underlines the value of this immunotherapeutic approach.
Recent developments in the identification and selection of tumor-specific T-cell populations have facilitated the implementation of TIL ACT also in nonmelanoma malignancies. Building on the experience of Ella Lemelbaum Institute, Sheba Medical Center with ACT TIL in the treatment of metastatic melanoma, the Dept. of Oncology, Tel HaShomer has expanded the use of TIL ACT following a reduced intensity, non-myeloablative, lymphodepleting induction regimen to metastatic Melanoma, Ovarian (OC) and Cervical cancer patients. The rationale supporting these studies is to further develop the ACT TIL procedure and expand its applicability to metastatic OC and cervical cancers.
Read the detailed description
The Sponsor is developing the ex-vivo expanded autologous Tumor Infiltrating Lymphocytes (TIL) as the Investigational Product (IP). Yet, the administration of the TIL cellular product can only be accomplished in the context of an Autologous, Adoptive Cell Therapy (ACT) procedure which is composed of the following steps:
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
- Early-stage follow-up until 30 days post-discharge
- Late-stage follow-up, such as CT scans, will be carried out four and twelve weeks after TIL administration, and then every 3 months thereafter for the first year after TIL therapy; for the second year and onwards, as clinically indicated.
- Conditions
- Metastatic Ovarian Cancer
- Being tested
- Fludarabine, Radiation, TIL administration, IL-2
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Reduced intensity, myeloablative, lymphodepleting regimen (25 mg/m2 for 3 days)
RadiationRadiation
Total Body Radiation (TBR) (2 Gray in a single treatment) for 1 day
TIL administrationBiological
TIL Administration
IL-2Drug
bolus high-dose (720,000 IU/kg) IL-2 is administered to the patients every 8 hours, to tolerance. A maximum of 10 doses are given to the patients.
| Study group | Role | What they receive |
|---|---|---|
| ACT TIL | Experimental | 1. Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
2. Preparation and administration of unselected or 4-1BB enriched TIL
3. Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient. Receives: Drug: Fludarabine; Radiation: Radiation; Biological: TIL administration; Drug: IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Tumor responses
Radiological follow up via CT to determine the sum of complete Responders (CR) + Partial Responders (PR) +Stable Disease (SD) as assessment by RECICT 1.1
Measured: 3 years
Assess adverse events using NCI CTCAE V.4.03 during treatment and follow up
adverse events will be assess using MCI CTCAE V.4.03 during treatment and follow up
Measured: 3 years
Secondary outcomes (4)
Overall survival (OS)
Overall survival is defined as the time from study entry until death from any cause
Measured: 3 years
Response Rate( RR)
Radiological follow up via CT to determine the sum of complete responders (CR) + Partial responders (PR) as assessed by RECICT 1.1
Measured: 3 years
Progression Free Survival (PFS)
Progression free survival according to RECICT 1.1
Measured: 3 years
Quality of Life (QoL)
assessment of Quality of Life (QoL) using disease specific modules of the EORTC QLQ-C30 (version 3.0)
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2018
- Study start21 Jan 2018
- Primary completion1 Feb 2021 (estimated)
- Study completion1 Feb 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Jacob Schachter MD,, Sheba Medical Center
- Investigators
- Jacob Schachter, Prof., Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03412526
- Sponsor's protocol ID
- SHEBA-16-3568-JS-TIL Ovarian
- Status last verified
- Apr 2019
- First submitted
- 21 Jan 2018
- Last updated
- 4 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: to be considered
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Ovarian
- ClinicalTrials.gov ID
- NCT03412526
- Acronym / sponsor ID
- SHEBA-16-3568-JS-TIL Ovarian
- Conditions
- Metastatic Ovarian Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 21 Jan 2018 (actual)
- Primary completion
- 1 Feb 2021 (estimated)
- Study completion
- 1 Feb 2022 (estimated)
- First posted
- 26 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) in combination with lymphodepletion and high-dose interleukin 2.
Most TIL ACT trials have been conducted as salvage therapy for patients who already had failed numerous treatments; many study participants presented with multiple metastases, frequently in visceral organs and even in the brain. The effectiveness of TIL ACT in eradicating metastatic tumors of the responding patients underlines the value of this immunotherapeutic approach.
Recent developments in the identification and selection of tumor-specific T-cell populations have facilitated the implementation of TIL ACT also in nonmelanoma malignancies. Building on the experience of Ella Lemelbaum Institute, Sheba Medical Center with ACT TIL in the treatment of metastatic melanoma, the Dept. of Oncology, Tel HaShomer has expanded the use of TIL ACT following a reduced intensity, non-myeloablative, lymphodepleting induction regimen to metastatic Melanoma, Ovarian (OC) and Cervical cancer patients. The rationale supporting these studies is to further develop the ACT TIL procedure and expand its applicability to metastatic OC and cervical cancers.
Detailed description
The Sponsor is developing the ex-vivo expanded autologous Tumor Infiltrating Lymphocytes (TIL) as the Investigational Product (IP). Yet, the administration of the TIL cellular product can only be accomplished in the context of an Autologous, Adoptive Cell Therapy (ACT) procedure which is composed of the following steps:
- Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day
- Preparation and administration of unselected or 4-1BB enriched TIL
- Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient.
- Early-stage follow-up until 30 days post-discharge
- Late-stage follow-up, such as CT scans, will be carried out four and twelve weeks after TIL administration, and then every 3 months thereafter for the first year after TIL therapy; for the second year and onwards, as clinically indicated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ACT TIL | Experimental | Drug: Fludarabine, Radiation: Radiation, Biological: TIL administration, Drug: IL-21. Reduced Intensity, non-myeloablative, lymphodepleting induction regimen using Fludarabine (25 mg/m2 for 3 days) followed by Total Body Radiation (TBR) (2 Gray as a single treatment) for 1 day 2. Preparation and administration of unselected or 4-1BB enriched TIL 3. Bolus high-dose (720,000 IU/kg) IL-2 will be administered to each patient every 8 hours, to tolerance. A maximum of 10 doses will be administered per patient. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Able to understand and sign the Informed Consent Form.
- Pathology confirmed epithelial Ovarian/Fallopian Tube/Primary Peritoneal carcinomatosis.
- For ovarian/peritoneal carcinoma: Platinum- resistant or platinum refractory disease (platinum-resistant disease is defined as disease-progression within 6 months of completion of prior platinum containing regimen, whereas platinum refractory disease is defined as disease progression while on platinum containing regimen or within 3 months from first line, adjuvant chemotherapy).
- Received and exhausted standard of care therapies for recurrent ovarian cancer and further chemotherapy lines have no proven added value. (For platinum resistant disease, received no more than 3 prior chemotherapy lines, whereas for platinum refractory disease received no more than 2 previous chemotherapy lines).
- Patients must have at least one lesion that is resectable for TIL generation.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| FludarabineReduced intensity, myeloablative, lymphodepleting regimen (25 mg/m2 for 3 days) | Drug | ACT TIL |
| RadiationTotal Body Radiation (TBR) (2 Gray in a single treatment) for 1 day | Radiation | ACT TIL |
| TIL administrationTIL Administration | Biological | ACT TIL |
| IL-2bolus high-dose (720,000 IU/kg) IL-2 is administered to the patients every 8 hours, to tolerance. A maximum of 10 doses are given to the patients. | Drug | ACT TIL |
Primary outcome
Objective Tumor responses
Time frame: 3 years
Radiological follow up via CT to determine the sum of complete Responders (CR) + Partial Responders (PR) +Stable Disease (SD) as assessment by RECICT 1.1
Assess adverse events using NCI CTCAE V.4.03 during treatment and follow up
Time frame: 3 years
adverse events will be assess using MCI CTCAE V.4.03 during treatment and follow up
4 secondary outcomes
Overall survival (OS)
Time frame: 3 years
Response Rate( RR)
Time frame: 3 years
Progression Free Survival (PFS)
Time frame: 3 years
Quality of Life (QoL)
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2019.
- Individual participant dataSharing planned: Undecided. to be considered
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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.
Jacob Schachter, Prof. principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Radiation and TIL administration in people with Metastatic Ovarian Cancer, run by Sheba Medical Center at 1 site in Israel.
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 32 inclusion and 0 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: status not confirmed, as of the sponsor's last update on 4 Apr 2019. 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 Israel. 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jacob Scachter, Prof. (972-3-5304907, jacob.schachter@sheba.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Tumor responses (time frame: 3 years). The study lists 2 primary outcomes in all. 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 4 Apr 2019.