Study Stopped
Study did not accrue any participants, the PI has left the institution.
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
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).
3 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
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.
Trial Health
Trial Health Score
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Started Jun 2015
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Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2015
CompletedFirst Submitted
Initial submission to the registry
June 10, 2015
CompletedFirst Posted
Study publicly available on registry
June 12, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2017
CompletedFebruary 17, 2016
February 1, 2016
1.7 years
June 10, 2015
February 15, 2016
Conditions
Outcome Measures
Primary Outcomes (2)
MTD of IP injections in combination with the IV fixed dose of aATC determined by the incidence of dose-limiting toxicity (DLT) defined using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Up to 4 weeks
Toxicity profile of IP and IV HER2Bi-aATC at the MTD or technically feasible dose graded using NCI CTCAE version 4.0
Patients who received any armed ATC but not evaluable for DLT will be analyzed separately for the toxicity profile. The toxicity will be summarized with point and exact confidence intervals.
Up to 2 years
Secondary Outcomes (8)
Changes in cytokine profiles
Baseline to up to 12 months
Changes in HAMA levels in serum samples
Baseline to up to 12 months
Changes in phenotyping induced by immunotherapy in peripheral blood mononuclear cells (PBMC)
Baseline to up to 12 months
Clinical response rate (including complete response, partial response, progressive disease, and stable disease) measured on the basis of CA-125 or RECIST-defined tumor measurements
Up to 12 months
Increases in IFN-gamma ELISPOTS
Baseline to up to 12 months
- +3 more secondary outcomes
Study Arms (1)
Treatment (aldesleukin, sargramostim, HER2Bi-aACT)
EXPERIMENTALPatients 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 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.
Interventions
Given SC
Given IV and IP
Correlative studies
Given SC
Eligibility Criteria
You may qualify if:
- 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 \[ECHO\])
- +18 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lawrence Lum
Barbara Ann Karmanos Cancer Institute
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 10, 2015
First Posted
June 12, 2015
Study Start
June 1, 2015
Primary Completion
February 1, 2017
Study Completion
February 1, 2017
Last Updated
February 17, 2016
Record last verified: 2016-02