Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent



Status:Recruiting
Conditions:Ovarian Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:2/13/2016
Start Date:June 2015
End Date:February 2017

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Treatment of High Risk or Recurrent Ovarian Cancer With Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells (BATs), Low Dose IL-2, and GM-CSF (Phase I).

This phase I trial studies the side effects and best dose of activated T-cell therapy when
given together with low-dose aldesleukin and sargramostim in treating patients with ovarian,
fallopian tube, or primary peritoneal cancer that is stage III-IV, has not responded to
previous treatment, or has come back. Activated T cells that have been coated with
bi-specific antibodies, such as anti-cluster of differentiation (CD)3 and anti-human
epidermal growth factor receptor 2 (HER2), may stimulate the immune system in different ways
and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor
cells. Colony-stimulating factors, such as sargramostim, may increase the production of
blood cells. Giving activated T-cell therapy with low-dose aldesleukin and sargramostim may
be a better treatment for ovarian, fallopian tube, or primary peritoneal cancer.

PRIMARY OBJECTIVES:

I. Perform a phase I clinical trial consisting of dose-escalation/de-escalation of
intraperitoneal (IP) infusions of anti-CD3 x anti-HER2/neu (HER2Bi) armed anti-CD3 activated
T cells (aATC) in women with high risk or recurrent ovarian cancer to determine the maximum
tolerated dose (MTD) for IP injections in combination with a fixed intravenous (IV) dose of
10 x 10^9 (± 20%) aATC once a week.

II. To clearly define the toxicity profile of IP and IV HER2Bi aATC at the MTD or
technically feasible dose in patients with ovarian cancer.

SECONDARY OBJECTIVES:

I. Evaluate clinical responses, time to progression, and overall survival. II. Evaluate
phenotype, cytokine profiles and interferon (IFN)-gamma enzyme-linked immunosorbent spots
(ELISPOTS), cytotoxicity and antibodies directed at laboratory ovarian cancer cell lines.

III. Monitor cancer antigen (CA)125 or tumor markers, and antibody responses to mouse
proteins (human anti-mouse antibodies [HAMA]).

IV. The migration of armed ATC out of the peritoneal and serum cytokine levels induced by IP
or IV armed ATC infusion will be assessed by studying the appearance of armed ATC at various
time points (0, 4, 8, 12, 24, 48, 72, and 96 hours after IP infusion) in the blood after IP
infusions by performing flow cytometry to detect anti-CD3 (OKT3) x anti-Her2 (Herceptin®)
bi-specific antibody (BiAb) on the surface of aATC.

OUTLINE: This is a dose-escalation study of IP infused HER2Bi-armed activated T cells.

Patients receive HER2Bi-aATC IV over 5-15 minutes and IP within 3-4 days of IV dose weekly
for 4 weeks. Patients also receive low-dose aldesleukin subcutaneously (SC) daily and
sargramostim SC twice weekly beginning 3 days before the first HER2Bi-aATC infusions
infusion and ending 7 days after the last HER2Bi-aATC infusion. Treatment continues in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 and 3 months, and then
every 6 months.

Inclusion Criteria:

- Histologically documented, epithelial ovarian, fallopian tube, or primary peritoneal,
high grade serous or clear cell carcinoma are eligible; all patients must have a
confirmed pathology; stage 3 and 4 initial disease with response to primary surgery
and neo/adjuvant chemotherapy, platinum refractory disease, and patients with
recurrent disease are candidates

- Patients meeting the above pathologic criteria will be eligible for therapy
irrespective of their HER2/neu over expression status; immunohistochemical staining
will be not be required for protocol entry but fluorescence in situ hybridization
(FISH) and immunohistochemistry (IHC) studies for HER2/neu are preferred

- Chemotherapy: no limit to prior therapies; however, patients with multiple
chemotherapy regimens will be screened for lymphocyte proliferation at investigator's
discretion

- Herceptin: women who have been previously treated with Herceptin or other monoclonal
antibody therapies are eligible for the trial

- Radiation therapy: patients who have received prior radiotherapy to any portion of
the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of
the breast, head and neck, or skin is permitted, provided that it was completed more
than three years prior to registration, and the patient remains free of recurrent or
metastatic disease

- Patients may have no evidence of measurable disease by Response Evaluation Criteria
in Solid Tumors (RECIST) criteria or have measurable disease; CA-125 and other
available markers will be obtained

- Karnofsky performance score of >= 70 is required or Eastern Cooperative Oncology
Group (ECOG) score, performance status (PS) = 0-2

- The patient must have a life expectancy of 3 months or more based on the judgment of
the investigators; women who have rapidly progressive symptomatic disease affecting
major organ systems such as the liver and lungs will be excluded

- Negative serum test for pregnancy in premenopausal women

- No previous or concurrent malignancy, other than curatively treated in situ squamous
cell carcinoma of the cervix or basal cell carcinoma of the skin or non-active breast
cancer

- Each patient must be aware of the nature of her disease process and must willingly
consent to treatment after being informed of alternatives, potential benefits, side
effects, and risks; eligibility testing that is considered standard of care may be
done prior to informed consent but no immunotherapy related procedures or testing may
occur without informed consent

- No serious medical or psychiatric illness which prevents informed consent or
intensive treatment

- Patients will be ineligible for treatment on this protocol if:

- There is a history of a recent myocardial infarction (within one year)

- There is a history of a past myocardial infarction (more than one year ago)
along with current coronary symptoms requiring medications and/or evidence of
depressed left ventricular function (left ventricular ejection fraction [LVEF] <
45% by echocardiogram [ECHO])

- There is a current history of angina/coronary symptoms requiring medications
and/or evidence of depressed left ventricular function (LVEF < 45% by ECHO)

- There is clinical evidence of congestive heart failure requiring medical
management (irrespective of ECHO results)

- Patients who have persistently elevated systolic blood pressures (BPs) >= 145 or
diastolic BPs >= 90 need to have their systolic or diastolic BP controlled with
anti-hypertensive agents for at least 3 days prior to the initiation of cell therapy;
patients already on anti-hypertensive agents will have their medicine adjusted based
on the clinical judgment of the patient care team

- Patients with treated brain metastases (received definitive radiation and/or
underwent surgical resection) are eligible for therapy on this protocol; patients
with clinical evidence of active brain metastases are ineligible for therapy on this
protocol

- Granulocytes >= 1,000/mm^3

- Platelet count >= 50,000/ul

- Hemoglobin >= 8 gm/dl

- Blood urea nitrogen (BUN) =< 1.5 times normal

- Serum creatinine =< 1.8 mg/dl

- Creatinine clearance >= 60 ml/mm

- Bilirubin =< 2.0 times normal

- Serum glutamic oxaloacetic transaminase (SGOT) =< 2.0 times normal

- Human immunodeficiency virus (HIV) = negative

- LVEF >= 45% at rest (by ECHO)

- Pulmonary function tests (PFT)-forced expiratory volume in one second (FEV1),
diffusing capacity of the lung for carbon monoxide (DLCO2), and forced vital capacity
(FVC) >= 60% predicted value if clinically indicated

- Minor changes from the required initial laboratory data guidelines will be allowed at
the discretion of the attending team under special circumstances; the reasons for
exceptions must be documented prior to enrollment

- Appropriate slides of the primary lesion will be available for future review; if
available, HER2/neu positivity will be recorded

- Peritoneal dialysis catheter implantation is identical to that from the Gynecologic
Oncology Group (GOG) 252 Protocol and revised from the GOG Surgical Procedures Manual
We found this trial at
1
site
4100 John R
Detroit, Michigan 48201
800-527-6266
Barbara Ann Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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mi
from
Detroit, MI
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