A Trial of Intravenous Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2A in Stage III or IV Ovarian Cancer

The University of Texas System (UT)

Status and phase

Terminated

Phase 2

Conditions

Extraovarian Peritoneal Cancer

Epithelial Ovarian Cancer

Fallopian Tube Carcinoma

Treatments

Drug: Denileukin Diftitox/SC Pegylated IFNα-2a

Study type

Interventional

Funder types

Other

Identifiers

NCT01773889

OCR 09-01 (Other Identifier)

HSC20090233H

Details and patient eligibility

About

This study will test the hypothesis that adding pegylated IFN (IFN)a-2b to denileukin diftitox improves the potential of denileukin diftitox alone to deplete regulatory T cells (Tregs) and will thereby boost tumor immunity in patients with advanced-stage epithelial ovarian cancers, enhancing treatment efficacy.

Full description

The aims of this study are to:

Assess the efficacy of adding pegylated IFN-α2b to denileukin diftitox to treat selected advanced-stage epithelial ovarian cancers Test the immune-modulating effects of adding pegylated IFN-α2b to denileukin diftitox in ovarian cancer patients and relate them to clinical efficacy Identify any toxicity associated with pegylated IFN-α2b plus denileukin diftitox treatment in these patients Identify practical means to dose the immunomodulating agents denileukin diftitox and pegylated IFN-α2b based on immunopharmacodynamic metrics

Enrollment

2 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Able to provide informed consent
Not on immune-modulating drugs, except those used as denileukin diftitox premedication, unless the principal investigator grants an exception (which exception must be documented in writing)
Histologically proven epithelial (non-germ cell, non-stromal cell) cancer of the ovaries, fallopian tubes or extraovarian peritoneal carcinoma. Clinical recurrence without documented pathology is acceptable
FIGO stage III or IV with failed prior first-line therapy, or ineligible for or intolerant of such therapy
Measurable disease as defined in section 6 within 30 days of study enrollment
Blood hemoglobin ≥ 8.5 gm/dl within 7 days of study enrollment
Absolute neutrophil count ≥ 750/mm3 within 7 days of study enrollment
Platelet count ≥ 40,000/mm3 within 7 days of study enrollment
SGOT (serum glutamic oxaloacetic transaminase) ≤10 x upper limit of normal within 7 days of study enrollment
Normal TSH (thyroid-stimulating hormone ) within 30 days of study enrollment
No chemotherapy in the 14 days prior or radiation therapy in the thirty days prior to initiation of treatment on this study
No other concurrent chemotherapy, surgery or radiation therapy during this protocol except surgery or radiation therapy to control symptoms with concurrence of the principal investigator
No contraindication to any study treatment
No active major medical problems, including untreated or uncontrolled infections
Beck Depression Index ≥15 within 30 days of study enrollment
If of reproductive potential, a negative urine pregnancy test within 3 days of study enrollment, and agreement to use adequate contraception. Pregnancy testing will continue monthly while on treatment unless the subject is no longer able to become pregnant or there is sufficient justification otherwise
Not breast feeding
Life expectancy ≥ six months
ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
Serum albumin ≥ 1.8 gm/dl
Age ≥ 18 years
Acceptable baseline retinal examination within 30 days of study enrollment
No active substance abuse in the prior 6 months
Patients failing single agent denileukin diftitox in the ongoing trial "A Phase II Trial of Intravenous Ontak to Treat Epithelial Ovarian Cancer FIGO Stage III or Stage IV, or Extraovarian Peritoneal Carcinoma, Failing or Ineligible for First-Line Therapy" are eligible for this trial provided that three or more weeks have elapsed since their last denileukin diftitox infusion and they meet all eligibility criteria and successfully undergo all screening examinations for this trial.

Exclusion criteria

Unable to tolerate phlebotomy
Germ cell or stromal cell cancers of the ovaries, or other currently uncured cancer
Active autoimmune disease including systemic lupus erythematosus, psoriasis, or inflammatory bowel disease that is not medically controlled
Autoimmune hepatitis, whether medically controlled or not
Contraindication to any study drug
Known hypersensitivity to denileukin diftitox, pegylated IFN-α2a or any of their components or excipients
Current pregnancy or breast feeding
Inability to document adequate contraception if a female of reproductive potential
On other immune-modulating drugs, except denileukin diftitox premedications or those approved by the principal investigator
Chemotherapy within 14 days or radiation therapy within the thirty days prior to initiation of study treatment
Life expectancy less than six months
Serum albumin < 1.8 gm/dl
Blood hemoglobin < 8.5 gm/dl
ECOG performance status> 2
Symptomatic coronary artery disease (including uncontrolled angina, congestive heart failure, and the like)
Uncontrolled hypertension (diastolic BP consistently >100 mm Hg or systolic BP consistently >160 mm Hg on a regular basis)
Uncontrolled, symptomatic cardiac arrhythmia
Retinopathy associated with significant visual impairment
Beck Depression Index >15
Active substance abuse in the prior 6 months