Cancer, Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer, Solid Tumor
Conditions
Brief summary
To determine the maximum tolerated dose (MTD) of FT538 monotherapy when administered via intraperitoneal (IP) catheter and in combination with intravenous (IV) enoblituzumab in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer.
Interventions
DRUGFT538
FT538 IP at assigned dose level on Day 1, Day 8, and Day 15.
BIOLOGICALEnoblituzumab
Enoblituzumab 15 mg/kg IV begin on Day -6 and continuing once every 3 weeks beginning on Day 22 until disease progression or unacceptable toxicity - refer to Section 7.2.1 for timing of the enoblituzumab dose on Day 22 if steroid pre-meds are needed due to an infusion reaction with the 1st enoblituzumab dose as there is a 14 day ban on corticosteroid use after the last dose of FT538
Sponsors
National Cancer Institute (NCI)
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer meeting one of the following minimal prior treatment requirements (no limit to the maximum number of prior treatments). * Platinum Resistant: may receive FT538 as 2nd line (as 1st salvage therapy). * At least 18 years of age at the time of consent. * GOG Performance Status 0, 1, or 2 (refer to Appendix I). * Adequate organ function within 14 days (28 days for pulmonary and cardiac) of study treatment (CY/Flu or enoblituzumab) start * Pulmonary Function: Oxygen saturation ≥ 90% on room air; PFTs are performed only if known history or as medically indicated - if done, must have pulmonary function \>50% corrected DLCO and FEV1. * Cardiac Function: LVEF ≥ 40% by echocardiography, MUGA, or cardiac MRI; no clinically significant cardiovascular disease including any of the following: stroke or myocardial infarction within 6 months prior to first study treatment; unstable angina or congestive heart failure of New York Heart Association (NYHA) Grade 2 or higher (Appendix I).
Exclusion criteria
* Pregnant or breastfeeding or planning on becoming pregnant in the next 6 months. * Currently receiving or likely to require systemic immunosuppressive therapy * Active autoimmune disease requiring systemic immunosuppressive therapy. * History of severe asthma and currently on chronic systemic medications. * Uncontrolled bacterial, fungal or viral infections with progression of clinical symptoms despite therapy. * Receipt of any biological therapy, chemotherapy, or radiation therapy (except palliative RT), within 2 weeks prior to the first dose of FT538 * Live vaccine within 6 weeks prior to start of lympho-conditioning. * Known allergy to the following FT538 components: albumin (human) or dimethyl sulfoxide (DMSO). * Prior enoblituzumab. * Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions in the 2-year period leading up to study enrollment. (Refer to Section 5.1.8 regarding history of brain metastases.) * Known history of HIV positivity or active hepatitis C or B - chronic asymptomatic viral hepatitis is allowed. * Presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to patient. * Any medical condition or clinical laboratory abnormality that, per investigator judgement, precludes safe participation in and completion of the study or that could affect compliance with protocol conduct or interpretation of results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Maximum Tolerated Dose (MTD) of FT538 | 48 months | The primary objective of the study is to determine the maximum tolerated dose (MTD) of FT538 monotherapy when administered via intraperitoneal (IP) catheter and in combination with intravenous (IV) enoblituzumab in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer. Monitor the patient for signs of acute infusion related reaction during and after IP infusion. For IV infusion signs of a possible reaction are rigors and chills, rash, urticaria, hypotension, dyspnea, and angioedema. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 72 months | Overall response rate is defined as number of patients who have a partial or complete response to therapy divided by the total number of patients who received treatment. |
| Determine Progression-free Survival (PFS) | 72 months | Number of participants experiencing progression free survival at one year follow up |
| Adverse Events | 72 months | Number of participants experiencing adverse events with the combination of Enoblituzumab and FT538 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumor Biopsies (if Feasible) at the Time of Catheter Placement and Catheter Removal for Study Related Analysis | 72 months | Tumors will be biopsied to assess tumor microenvironment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IP FT538 Monotherapy Level -1: IP FT538 monotherapy 5 x 10\^7 cells/dose Level 1: IP FT538 monotherapy 1 x 10\^8 cells/dose Level 2: IP FT538 monotherapy 3 x 10\^8 cells/dose Level 3: IP FT538 monotherapy 1 x 10\^9 cells/dose Level 4: IP FT538 monotherapy 1.5 x 10\^9 cells/dose
FT538: FT538 IP at assigned dose level on Day 1, Day 8, and Day 15. | 1 |
| IP FT538 + Enoblituzumab Level 5: IP FT538 at the safe dose (MTD-1) + Enoblituzumab Level 6: IP FT538 at the highest dose (MTD) + Enoblituzumab
FT538: FT538 IP at assigned dose level on Day 1, Day 8, and Day 15.
Enoblituzumab: Enoblituzumab 15 mg/kg IV begin on Day -6 and continuing once every 3 weeks beginning on Day 22 until disease progression or unacceptable toxicity - refer to Section 7.2.1 for timing of the enoblituzumab dose on Day 22 if steroid pre-meds are needed due to an infusion reaction with the 1st enoblituzumab dose as there is a 14 day ban on corticosteroid use after the last dose of FT538 | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | IP FT538 Monotherapy | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Determine Maximum Tolerated Dose (MTD) of FT538
The primary objective of the study is to determine the maximum tolerated dose (MTD) of FT538 monotherapy when administered via intraperitoneal (IP) catheter and in combination with intravenous (IV) enoblituzumab in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer. Monitor the patient for signs of acute infusion related reaction during and after IP infusion. For IV infusion signs of a possible reaction are rigors and chills, rash, urticaria, hypotension, dyspnea, and angioedema.
Time frame: 48 months
Population: Trial was terminated before the outcome measure data were collected.
Secondary
Adverse Events
Number of participants experiencing adverse events with the combination of Enoblituzumab and FT538
Time frame: 72 months
Population: Trial was terminated before the outcome measure data were collected.
Secondary
Determine Progression-free Survival (PFS)
Number of participants experiencing progression free survival at one year follow up
Time frame: 72 months
Population: Trial was terminated before the outcome measure data were collected.
Secondary
Overall Response Rate (ORR)
Overall response rate is defined as number of patients who have a partial or complete response to therapy divided by the total number of patients who received treatment.
Time frame: 72 months
Population: Trial was terminated before the outcome measure data were collected.
Other Pre-specified
Tumor Biopsies (if Feasible) at the Time of Catheter Placement and Catheter Removal for Study Related Analysis
Tumors will be biopsied to assess tumor microenvironment.
Time frame: 72 months
Population: Trial was terminated before the outcome measure data were collected.