AzTrials
AzTrials

Malignant Ovarian Clear Cell TumorPhase 1NCT02470559

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

A Phase 1 study testing Aldesleukin, HER2Bi-Armed Activated T Cells and Laboratory Biomarker Analysis in people with Malignant Ovarian Clear Cell Tumor and Malignant Ovarian Serous Tumor, run by Barbara Ann Karmanos Cancer Institute.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Aldesleukin, HER2Bi-Armed Activated T Cells and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2015to Feb 2017
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

  • 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
Show all 33Show fewer
  • 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

Who cannot join

None listed.

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Aldesleukin, HER2Bi-Armed Activated T Cells, Laboratory Biomarker Analysis, Sargramostim
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

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

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given SC

  • HER2Bi-Armed Activated T CellsBiological

    Also called Anti-CD3 x Anti-Her2/neu Bispecific Antibody-Armed Activated T Cells, HER2Bi-Armed ATCs

    Given IV and IP

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • SargramostimBiological

    Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine

    Given SC

Study groups in NCT02470559
Study groupRoleWhat they receive
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.
Receives: Biological: Aldesleukin; Biological: HER2Bi-Armed Activated T Cells; Other: Laboratory Biomarker Analysis; Biological: Sargramostim

What is being measured

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

  1. 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

    Measured: Up to 4 weeks

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (8)

  1. Changes in cytokine profiles

    Increases or decreases in the amount of cytokine produced from the pre immunotherapy baseline at any time point after immunotherapy will be considered as continuous outcomes. Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

    Measured: Baseline to up to 12 months

  2. Changes in HAMA levels in serum samples

    Sera from patients will be obtained before and after immunotherapy at the designated time points to determine if there is development of HAMA responses directed at OKT3 (mouse IgG2a antibody). Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

    Measured: Baseline to up to 12 months

  3. Changes in phenotyping induced by immunotherapy in peripheral blood mononuclear cells (PBMC)

    PBMC from the patients will be obtained before and after immunotherapy to determine if there changes induced by immunotherapy. Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

    Measured: Baseline to up to 12 months

  4. 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

    Point and exact confidence interval estimates will be calculated for response rate.

    Measured: Up to 12 months

  5. Increases in IFN-gamma ELISPOTS

    Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

    Measured: Baseline to up to 12 months

  6. Increases in the immunoglobulin G titer against selected ovarian cancer cell lines in serum samples

    Sera from patients will be obtained before and after immunotherapy to determine if there are changes induced by immunotherapy. Paired t-test or Wilcoxon signed rank test will be used to compare the difference between baseline and after any time point of aATC treatment in proliferation, ELISPOTS, and the amount of cytokine produced. The data collected at all study time points after immunotherapy will be analyzed using mixed-effect model for longitudinal data adjusted for baseline measures.

    Measured: Baseline to 4 weeks

  7. Overall survival

    Will be estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 6 month, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates will be calculated.

    Measured: From the beginning of immunotherapy to the time of death, assessed up to 12 months

  8. Progression free survival

    Will be estimated with the standard Kaplan-Meier method, from which summary statistics of interest (median, 6 month, 1-year rate, etc.) will be derived. Both point and 95% confidence interval estimates will be calculated.

    Measured: From the beginning of immunotherapy to progression or death, assessed up to 12 months

Timeline

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

  1. First posted12 Jun 2015 (estimated)
  2. Study startJun 2015
  3. Primary completionFeb 2017 (estimated)
  4. Study completionFeb 2017 (estimated)

Why it stopped: Study did not accrue any participants, the PI has left the institution.

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02470559
Sponsor's protocol ID
2014-129
Other IDs
NCI-2015-00180, 2014-129, P30CA022453
Status last verified
Feb 2016
First submitted
10 Jun 2015
Last updated
17 Feb 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Aldesleukin, HER2Bi-Armed Activated T Cells and Laboratory Biomarker Analysis in people with Malignant Ovarian Clear Cell Tumor and Malignant Ovarian Serous Tumor, run by Barbara Ann Karmanos Cancer Institute.

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 33 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: withdrawn, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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?

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 (time frame: Up to 4 weeks). 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?

On the ClinicalTrials.gov record for NCT02470559.

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 17 Feb 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in