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Ovarian CancerPhase 1NCT02118285

Intraperitoneal Natural Killer Cells and INCB024360 for Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

A Phase 1 study testing Fludarabine, Cyclophosphamide and NK cells in people with Ovarian Cancer and Fallopian Tube Carcinoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a single center phase I trial designed to determine the maximum tolerated dose (MTD) of the oral IDO inhibitor INCB024360 when administered as part of a larger regimen of intraperitoneal (IP) delivery of haploidentical donor NK cells and IL-2 after a non-myeloablative cyclophosphamide/fludarabine (Cy/Flu)… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Fludarabine, Cyclophosphamide and NK cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
28 Jul 2014to 12 Nov 2015
Phase
Phase 1
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer that has failed or progressed after at least 1 prior salvage chemotherapy regimen directed at recurrent/metastatic disease.
  • Measurable disease per disease specific RECIST version 1.1- patients with bone as their only site of disease will not be eligible
  • If history of brain metastases must be stable for at least 3 months after treatment - A brain CT scan will only be required in subjects with known brain metastases at the time of enrollment or in subjects with clinical signs or symptoms suggestive of brain metastases.
  • Available related HLA-haploidentical NK cell donor by at least Class I serologic typing at the A\&B locus
  • Age 18 years or older
  • GOG Performance Status ≥ 2 - refer to appendix III
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  • Adequate organ function as determined by the following criteria within 14 days of the start of the preparative regimen, unless otherwise noted:
  • Bone marrow: platelets ≥ 80,000 x 109/L and hemoglobin ≥ 9 g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 109/L, unsupported by G-CSF or granulocytes
  • Renal function: estimated glomerular filtration rate (GFR) of ≥ 50 ml/min (based on the Fairview Laboratories formula at time of screening)
  • Liver function: total bilirubin < 1.5 times upper limit of institutional normal; AST, ALT, and alkaline phosphatase < 3 times upper limit of institutional normal
  • Cardiac: Left ventricular ejection fraction > 40% (within 28 days of treatment start)
  • Pulmonary function: > 50% corrected DLCO and FEV1, if presence of pleural effusion due to metastatic disease > 40% corrected DLCO and FEV1 is acceptable (within 28 days of treatment start)
  • Able to be off prednisone or other immunosuppressive medications other than that prescribed per protocol for at least 3 days prior to Day 0
  • At least 14 days must lapse between last prior anti-cancer treatment and 1st day of preparative regimen
  • Not pregnant or lactating - The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Participants of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy and agree to use adequate birth control during study treatment.
  • Able to tolerate intraperitoneal (IP) port placement and IP treatment administration in the opinion of the enrolling investigator
  • Voluntary written consent

Who cannot join

  • Active infection - must be afebrile and off antibiotics
  • Receiving monoamine oxidase inhibitors (MAOI)s or drug which as significant MAOI activity (meperidine, linezolid, methylene blue) within 21 days of 1st dose of fludarabine
  • Requiring potent CYP3A4 inducers or inhibitors
  • Have ever had Serotonin Syndrome after receiving one or more serotonergic drugs
  • Prior therapy with anti-CTLA-4 antibody, anti PD-1, or an experimental immune system-targeted therapy
  • Use of any UGT1A9 inhibitor including: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid from screening through follow-up period.
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  • Undergone an organ transplant(s) including allogeneic stem cell or bone marrow transplants.
  • Unstable cardiovascular disease (eg, uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatment.
  • Any gastrointestinal condition causing malabsorption or obstruction (eg, celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome). Unable or unwilling to swallow tablets BID.
  • Active autoimmune process (eg rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) or who have been receiving therapy for an autoimmune or inflammatory disease. Vitiligo, thyroiditis, or eczema is permitted if patient is otherwise eligible
  • Known HIV-positivity
  • History of hepatitis or positive serology as follows:
  • Hepatitis B (HepB) screening testing required:
  • HepB SAg (hepatitis B surface antigen);
  • Anti-HepB SAg (antibody against hepatitis B surface antigen);
  • Anti-Hepatitis B core IgG (antibody against hepatitis B core antigen).
  • Hepatitis B core IgM antibody
  • Hepatitis C screening testing required:
  • HCV-antibody (antibody against hepatitis C virus);
  • HCV-RNA (serum test for circulating virus, based on detecting RNA)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Minnesota Masonic Cancer Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Indoleamine-2,3-dioxygenase (IDO) Inhibition With INCB024360 and Intraperitoneal Delivery of Allogeneic Natural Killer Cells for Women With Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

This is a single center phase I trial designed to determine the maximum tolerated dose (MTD) of the oral IDO inhibitor INCB024360 when administered as part of a larger regimen of intraperitoneal (IP) delivery of haploidentical donor NK cells and IL-2 after a non-myeloablative cyclophosphamide/fludarabine (Cy/Flu) preparative regimen for the treatment of recurrent ovarian, fallopian tube, and primary peritoneal cancer.

Read the detailed description

Haploidentical donor NK cells and the 1st dose of IL-2 are infused intraperitoneally (IP) after a non-myeloablative preparative regimen of cyclophosphamide and fludarabine. IP IL-2 continues three times a week for 5 additional doses. INCB024360, at the assigned dose, begins 2 days before the NK cell infusion (on day -2) and continues twice daily for 90 days.

Follow-up for disease response and survival is for 1 year from the NK cell infusion with the possibility of re-treatment for patients who experience at least a clinical benefit for a minimum of 6 months prior to disease progression.

The MTD of INCB024360 will be determined using the continual reassessment method (CRM). The 1st 2 patients will be enrolled at dose level 1 (50 mg bid) of INCB024360. Each new cohort of 2 patients will be sequentially assigned to most appropriate dose by the study statistician based on the updated toxicity profile. Up to 4 dose levels of INCB024360 will be tested (50, 100, 200, and 300 mg bid) with a dose level -1 (25 mg bid) used in the event that 50 mg bid proves to be too toxic. The MTD will be identified when the total sample size of 20 patients is exhausted.

Being tested
Fludarabine, Cyclophosphamide, NK cells, IL-2, INCB024360
Keywords
Ovarian cancer, Fallopian cancer, Primary peritoneal cancer
Medical subject headings
Ovarian Neoplasms, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludara

    Fludarabine 25 mg/m^2 IV on days -6 through -2 from NK cell infusion

  • CyclophosphamideDrug

    Also called Endoxan, Cytoxan, Neosar, Procytox

    Cyclophosphamide 30 mg/kg IV on days -5 and -4 from NK cell infusion

  • NK cellsBiological

    Also called Natural Killer Cells

    CD3-/CD19- selected NK cells administered by intraperitoneal (IP) infusion on day 0

  • IL-2Biological

    Also called Interleukin 2

    IL-2 at 6 million units/dose IP 3 times a week x 6 doses with the 1st dose given immediately after the NK cell infusion

  • INCB024360Drug

    INCB024360 at assigned dose by mouth twice a day begin day -2 and continue for 90 days (+/- 3 days)

Study groups in NCT02118285
Study groupRoleWhat they receive
TreatmentExperimentalHaploidentical donor NK cells and IL-2 are infused intraperitoneally (IP) after a non-myeloablative preparative regimen of cyclophosphamide and fludarabine. INCB024360, at the assigned dose, begins 2 days before the NK cell infusion and continues twice daily for 90 days.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: NK cells; Biological: IL-2; Drug: INCB024360

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose of INCB024360

    To determine the maximum tolerated dose (MTD) of INCB024360 when administered with intraperitoneal haploidentical donor NK cells/IL-2 after a nonmyeloablative cyclophosphamide/fludarabine (Cy/Flu) preparative regimen in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer

    Measured: 90 days

Secondary outcomes (4)

  1. Initial tumor response

    The proportion of patients with initial tumor response (CR or PR)

    Measured: 90 days

  2. Duration of tumor response

    Duration of tumor response

    Measured: 1 year

  3. Progression-free survival

    Average time to progression.

    Measured: 5 years

  4. Overall survival

    Average length of survival after treatment

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Apr 2014 (estimated)
  2. Study start28 Jul 2014
  3. Primary completion12 Nov 2015
  4. Study completion12 Nov 2015

Resources

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
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02118285
Sponsor's protocol ID
2012LS101
Other IDs
MT2013-11
Status last verified
Dec 2017
First submitted
26 Mar 2014
Last updated
5 Dec 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fludarabine, Cyclophosphamide and NK cells in people with Ovarian Cancer and Fallopian Tube Carcinoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

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 17 inclusion and 20 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 5 Dec 2017. 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 United States. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose of INCB024360 (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02118285.

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 5 Dec 2017.

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