ALT-803 in Treating Patients with Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Status: Active

Description

This randomized phase II trial studies how well superagonist interleukin-15:interleukin-15 receptor alphaSu / Fc fusion complex ALT-803 (ALT-803) works in treating patients with stage III-IV ovarian, fallopian tube, or primary peritoneal cancer. Biological therapies, such as ALT-803, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. ALT-803 is usually given as an injection under the skin (subcutaneous); however, ovarian, fallopian tube, and primary peritoneal cancers give the unique opportunity to administer drugs directly into the belly, referred to as an intraperitoneal infusion. It is not yet known if intraperitoneal infusion of ALT-803 works better than subcutaneous injection in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Eligibility Criteria

Inclusion Criteria

  • Diagnosis of Federation of Gynecology and Obstetrics (FIGO) stage III or grade IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma, has received at least 3 cycles of first line intravenous (IV)/IP cisplatin and paclitaxel chemotherapy and has stable disease or better as defined by measurable/evaluable tumor and/or CA-125 levels
  • Able to begin study therapy within 3 weeks (+/- 1 week) of final IV/IP chemotherapy
  • Functioning intraperitoneal catheter
  • Gynecological Oncology Group (GOG) performance status =< 2
  • hemoglobin > 8 g/dl
  • Absolute neutrophil count (ANC) >= 1500/ul
  • Absolute lymphocyte count (ALC) > 800/ul
  • Platelets > 50 x 10^9/L
  • Creatinine: =< 2.0 mg/dL
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 3 x upper limit of institutional normal (ULN)
  • Ability to be off prednisone and other immunosuppressive drugs (< 1 mg/day) for at least 3 days prior to and while receiving ALT-803
  • Available archived tumor (formalin-fixed, paraffin-embedded tissue block) for genomic and proteomic analysis
  • Voluntary written consent prior to the performance of any research related procedures

Exclusion Criteria

  • Received any investigational agent within the 14 days before the start of ALT-803
  • Class II or greater New York Heart Association Functional Classification criteria or serious cardiac arrhythmias likely to increase the risk of cardiac complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
  • Marked baseline prolongation of QT/corrected QC (QTc) interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
  • Uncontrolled bacterial, fungal or viral infections including human immunodeficiency virus (HIV)-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed
  • Active autoimmune disease requiring systemic immunosuppressive therapy
  • History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible)
  • Uncontrolled hypertension defined as an average systolic blood pressure of >= 140 mm Hg or an average diastolic pressure >= 95 mm Hg
  • History of pulmonary disease or abnormal pulmonary function studies
  • History of narcolepsy or any neurological condition which may impair consciousness

Locations & Contacts

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Contact: Melissa A. Geller
Phone: 612-626-3111
Email: gelle005@umn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To select a “winner” for future study with the intent to ensure that if one method is clearly inferior in terms of the primary endpoint of progression free survival (PFS) by 6 months of subcutaneous administration against intraperitoneal and subcutaneous administration of ALT-803.

SECONDARY OBJECTIVES:

I. To determine one and two year progression free survival (PFS).

II. To determine one and two year overall survival (OS).

III. To document ALT-803 associated toxicity when administered by intraperitoneal (IP) in this patient population.

IV. To evaluate the safety of ALT-803 when administered by IP on this schedule.

TERTIARY OBJECTIVES:

I. To evaluate peripheral blood and peritoneal washing lymphocyte number, phenotype and function.

II. To characterize ALT-803 immunogenicity.

III. To determine the genomic, transcriptomic, and proteomic profile of subjects’ tumors to identify gene mutations, gene amplifications, ribonucleic acid (RNA)-expression levels, and protein-expression levels.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ALT-803 subcutaneously (SC) on days 1, 8, 15, and 22. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ALT-803 IP on days 1, 8, 15, and 22 of course 1 only and then SC on days 1, 8, 15, and 22 of courses thereafter. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 weeks for 2 years from the start of treatment.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Minnesota / Masonic Cancer Center

Principal Investigator
Melissa A. Geller

Trial IDs

Primary ID 2016LS034
Secondary IDs NCI-2017-01337
Clinicaltrials.gov ID NCT03054909