Intraperitoneal Infusion of Autologous Monocytes With Sylatron (Peginterferon Alfa-2b) and Actimmune (Interferon Gamma-1b) in Women With Recurrent or Refractory Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer

Phase 1

Terminated

Conditions: Primary Peritoneal Cancer
Fallopian Tube Cancer
Ovarian Cancer

Interventions: Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON

Registration Number: NCT02948426

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Ovarian cancer is a leading cause of cancer death in women. Monocytes are white blood cells that slow tumor growth. Interferons (IFNs) are molecules that help immune cells fight cancer. Researchers want to stimulate monocytes with IFNs. They want to test if these stimulated monocytes combined with the drugs Sylatron and Actimmune can shrink tumors and slow the progression of cancer.

Objective:

To test how well IFN stimulated monocytes, with Sylatron and Actimmune, kill tumor cells.

Eligibility:

Women ages 18 and older with certain ovarian, fallopian tube, or peritoneal cancers

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Scan

Results or sample from previous biopsy

Participants may have a tumor sample taken.

Participants who do not have a port will have a catheter placed inside the abdominal cavity. It will be used to give the treatment.

Participants will have visits for 4 days of each 28-day cycle. This includes overnight observation.

Participants with ascites fluid in their abdominal cavity will have it sampled twice.

Each cycle, participants will have:

Blood tests

Leukapheresis. Some blood is removed and put through a machine that separates out the monocytes. The rest of the blood is returned to the body.

Infusion of the monocytes and study drugs

Participants will have weekly phone calls in Cycle 1 and scans every 2 cycles.

Participants will continue treatment until they can no longer tolerate it or their cancer gets worse.

Participants will have a visit about 1 month after stopping treatment, then monthly phone calls.

Detailed Description: Background:

* Monocytes can differentiate into classic M1 (classically activated) macrophages inhibiting tumor proliferation and promoting natural killer (NK) cell differentiation.

* Human alpha interferons (interferon alfa, IFN-alpha), interferon gamma (IFN-gamma) and monocytes have strong anti-neoplastic response in vitro and in vivo

* IFN-alpha and IFN-gamma have been shown in early phase clinical trials to be safely administered intraperitoneally.

* Intraperitoneal monocytes alone or activated with IFN-gamma are safe and feasible as demonstrated in phase I clinical studies.

* We have shown that the combination of human monocytes, IFN-alpha2a and IFN-gamma1b, or pegylated IFN-alpha, act synergistically against tumor cells in vitro and in mouse models.

Objectives:

-To identify a maximum tolerated dose of intraperitoneal autologous monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b).

Eligibility:

* Advanced metastatic or unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is relapsed and resistant or refractory to prior platinum-based standard care systemic regimen.

* Patients must be off prior chemotherapy, radiation therapy, hormonal therapy or biological therapy for at least 4 weeks.

* Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and adequate organ and marrow function.

Design:

* This is an open label single arm phase I trial to determine the maximum tolerated dose of intraperitoneal monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b).

* Autologous monocytes obtained through apheresis will be mixed with Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b) in a 3 + 3 dose escalation and administered intraperitoneally once every 28 days. A new product will be manufactured for each treatment cycle.

* Once the maximum tolerated dose is obtained, an expansion cohort will be enrolled to better quantify response rate and time to disease progression.

* Research samples including peripheral blood and ascites will be obtained prior to the initiation of study therapy andprior to the start of each cycle. Tissue biopsies will be obtained in the dose expansion phase to characterize the immune infiltration.

* Patients will be evaluated every 2 cycles for response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and every cycle for safety using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Level 1 - Sylatron 25µg (0.1 µg/ml); Actimmune 5mg (0.02µg/ml)	Autologous Monocytes + ACTIMMUNE + SYLATRON	Sylatron 25µg (0.1 µg/ml); Actimmune 5mg (0.02µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.
Dose Level 3 - Monocytes (750x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml)	Autologous Monocytes + ACTIMMUNE + SYLATRON	Monocytes (750x10\^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.
EX1 Dose Expansion Arm	Autologous Monocytes + ACTIMMUNE + SYLATRON	10 additional patients will be treated at the maximum tolerated dose (MTD)
Dose Level 2 - Monocytes (75x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml)	Autologous Monocytes + ACTIMMUNE + SYLATRON	Monocytes (75x10\^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.
Dose Level 4 - Monocytes (750x10^6); Sylatron 250µg (1µg/ml); Actimmune 50mg (0.2µg/ml)	Autologous Monocytes + ACTIMMUNE + SYLATRON	Monocytes (750x10\^6); Sylatron 250µg (1µg/ml); Actimmune 50mg (0.2µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.

Primary Outcome Measures

Name	Time	Method
Overall Maximum Tolerated Dose of Sylatron (Peginterferon Alpha-2b)	Cycle 1 Day 28	Maximum Tolerated Dose of Sylatron (Peginterferon alpha-2b).
Overall Maximum Tolerated Dose of Intraperitoneal Autologous Monocytes	Cycle 1 Day 28	Maximum Tolerated Dose of intraperitoneal autologous monocytes.
Overall Maximum Tolerated Dose of Actimmune (Interferon Gamma-1b)	Cycle 1 Day 28	Maximum Tolerated Dose of Actimmune (Interferon gamma-1b).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Response	Participants were evaluated for response by radiographic imaging every 8 weeks, up to 80 weeks	Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
Time to Disease Progression	Participants were assessed every 4 weeks by physical exam and 8 weeks by radiographic imaging for disease progression, up to 10 months.	Time to disease progression is defined as the time from registration to progression, censored at date last known progression-free for those who have not progressed. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study