IP ALT-803 Followed by SQ ALT-803 for Ovarian Cancer

QUILT-2.021: Randomized Study of Single Course of Intraperitoneal (IP) ALT-803 Followed by Subcutaneous (SQ) Maintenance ALT-803 Versus Subcutaneous (SQ) Maintenance ALT-803 Only After 1st Line Chemotherapy for Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

This is a single center, randomized phase II study of an IL-15Rα-Fc super-agonist complex (ALT-803) given as maintenance therapy after the completion of 1st line IV/IP chemotherapy for the treatment of advanced ovarian, fallopian tube, and primary peritoneal cancer.

Study Overview

• Status: Completed
• Conditions: FIGO Stage III and IV Ovarian Cancer; FIGO Stage III and IV Fallopian Tube Cancer; FIGO Stage III Primary Peritoneal Cancer
• Intervention / Treatment: Biological: ALT-803 Subcutaneous; Biological: ALT-803 Intraperitoneal

Detailed Description

In this study all patients receive four 8 week cycles of ALT-803 consisting of 4 weekly doses followed by a 4 week rest (no treatment). As it is not known how intraperitoneal (IP) administration (a route of drug administration frequently used for gynecologic cancers) of ALT-803 compares to subcutaneous (SQ) administration, both routes of administration will be tested. The primary objective of this trial is to select one method of delivery for further testing.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Diagnosis of FIGO stage III or grade IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma, has received at least 3 cycles of first line IV/IP cisplatin and paclitaxel chemotherapy and has stable disease or better - refer to Appendix II for FIGO staging system (Note: to be eligible for this study, the patient must receive a minimum of 3 cycles of IP therapy; however, patients may continue on IV only 1st line therapy for additional cycles as long as inclusion criteria 4.1.2 is met)
• Able to begin study therapy within 3 months of final dose of first line chemotherapy
• Functioning intraperitoneal catheter
• ≥ 18 years of age
• GOG performance status ≤ 2 (Appendix II)

• Adequate organ function within 14 days of enrollment defined as:

  • Hematology: hemoglobin ≥ 8 g/dl, absolute neutrophil count (ANC) ≥ 1500/ul, platelets ≥ 50 x 109/L
  • Creatinine: ≤ 2.0 mg/dL
  • Hepatic: SGOT and SGPT ≤ 3 x upper limit of institutional normal (ULN)
• Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to and while receiving ALT-803
• 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 (Appendix II) 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/QTc interval (e.g. demonstration of a QTc interval greater than 500 milliseconds)
• Uncontrolled bacterial, fungal or viral infections including 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 ≥2 readings over 160 mmHg systolic or 110 mmHg diastolic within month prior to enrollment despite optimal anti-hypertensive medication. Patients with high readings which improve to ≤160/110 after adjustment of medications will be eligible.
• History of pulmonary disease or abnormal pulmonary function studies
• History of narcolepsy or any neurological condition which may impair consciousness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: ALT-803 subcutaneous only	Biological: ALT-803 Subcutaneous; Patient receives ALT-803 10 mcg/kg subcutaneous weekly x 4 followed by 4 weeks of no treatment before continuing with treatment courses 2, 3, and 4. Treatment courses 2, 3, and 4 are identical for all patients - ALT-803 10 mcg/kg subcutaneous weekly x 4 with a 4 week rest (4 weeks on/4 weeks off)
Experimental: Arm 2: ALT-803 intraperitoneal and subcutaneous	Biological: ALT-803 Intraperitoneal; Patient receives ALT-803 10 mcg/kg intraperitoneal weekly x 4 weeks followed by 4 weeks of no treatment before continuing with treatment courses 2, 3, and 4. Treatment courses 2, 3, and 4 are identical for all patients - ALT-803 10 mcg/kg subcutaneous weekly x 4 with a 4 week rest (4 weeks on/4 weeks off).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Incidence of Progression Free Survival after first treatment of ALT-803.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Incidence of Progression Free Survival after first treatment of ALT-803.. Survival probability estimate.	1 year
Overall Survival	Overall Survival from start of ALT-803 dosing	1 year
ALT-803 Associated Toxicities	Incidence of ALT-803 associated toxicities after first treatment of ALT-803.	1 year
Incidence of Recorded Toxicity Grade 3 or Greater	Grade 3 adverse events or greater will be measured. A Grade 3 adverse event is defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling.	1 year
Progression Free Survival	Incidence of Progression Free Survival after first treatment of ALT-803.. Survival probability estimate.	2 years
Overall Survival	Overall Survival after first treatment of ALT-803.	2 year

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Melissa Geller, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2017
• Primary Completion (Actual): February 16, 2022
• Study Completion (Actual): February 16, 2022

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: February 13, 2017
• First Posted (Actual): February 16, 2017

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 2016LS034

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No