Denileukin Diftitox in Treating Patients With Advanced Refractory Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00357448

Purpose

RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of denileukin diftitox when given as an intraperitoneal infusion in treating patients with advanced refractory ovarian epithelial cancer, primary peritoneal cavity cancer, or fallopian tube cancer.

Condition	Intervention	Phase
Fallopian Tube Cancer Ovarian Cancer Peritoneal Cavity Cancer	Biological: denileukin diftitox	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	Phase I Dose Escalation Study of Intraperitoneal (I.P.) ONTAK Administered to Patients With Advanced Stage Ovarian Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Denileukin diftitox

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety and toxicity profile as measured by the Cancer Therapy Evaluation Program (CTEP), Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy (25% reduction in T-regulatory cells) as measured by the number of T-regulatory cells from baseline in either the peripheral blood and/or peritoneum [ Designated as safety issue: No ]
Serial measurements of CA-125 levels at baseline, monthly for 3 months, and then at 6 months to assess clinical impact on the disease [ Designated as safety issue: No ]
Changes in circulating cytokine levels in the peripheral blood and peritoneum as measured by ELISA at baseline and after treatment [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	April 2005
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Estimate the maximum tolerated dose of intraperitoneal administration of denileukin diftitox in patients with advanced refractory ovarian epithelial, primary peritoneal cavity, or fallopian tube cancer.

Secondary

Evaluate the change in the number of T-regulatory cells in the peritoneum and peripheral blood of patients treated with intraperitoneal denileukin diftitox.
Assess the clinical impact of denileukin diftitox on tumor burden by serial measurements of CA-125 in these patients.
Assess the level of circulating cytokines (aldesleukin, interleukin [IL]-6, IL-10, transforming growth factor [TGF]-β2, and tumor necrosis factor [TNF]-α) in the peritoneum and peripheral blood before and after treatment.

OUTLINE: This is a non-randomized, dose-escalation study.

Patients receive intraperitoneal denileukin diftitox over 15 minutes on days 1-3. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of denileukin diftitox until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After the completion of study treatment, patients are followed at 1 and 2 weeks, monthly for 3 months, and then at 6 months.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed ovarian epithelial carcinoma, primary peritoneal cavity carcinoma, or fallopian tube epithelial carcinoma with any of the following histologic epithelial cell types :
- Serous adenocarcinoma
- Endometrioid adenocarcinoma
- Mucinous adenocarcinoma
- Undifferentiated carcinoma
- Clear cell adenocarcinoma
- Transitional cell carcinoma
- Mixed epithelial carcinoma
Advanced refractory disease
- Unable to achieve first complete remission (CR) with first- or second-line chemotherapy OR relapsed after achieving second CR
Must have received prior chemotherapy comprising platinum-based regimen and paclitaxel
Must have undergone primary debulking surgery
No moderate (symptomatic requiring the use of diuretics) or severe (symptomatic requiring paracentesis or other invasive intervention) ascites

PATIENT CHARACTERISTICS:

Zubrod or SWOG performance status 0-2
WBC > 3,000/mm³
Lymphocyte count > 1,000/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 2.5 mg/dL
ALT and AST ≤ 2.5 times upper limit of normal (ULN)
Bilirubin ≤ 2.0 times ULN
Albumin ≥ 3.0 g/dL
Recovered from major infections
Must have a peritoneal catheter suitable for intraperitoneal infusion
No significant active concurrent medical illness precluding protocol treatment
No other concurrent malignancy requiring active treatment
No known history of any of the following:
- Hypersensitivity to diphtheria toxin or aldesleukin
- Active autoimmune disease (including hypothyroidism)
- Pulmonary disease except controlled asthma
- Significant cardiac disease
No clinical or radiological evidence of acute bowel obstruction within the past 30 days

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior surgical procedures
More than 30 days since prior chemotherapy
No prior denileukin diftitox

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357448

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Clinical Trials Office - Fred Hutchinson Cancer Research Cente 800-804-8824
Tumor Vaccine Group at the University of Washington	Recruiting
Seattle, Washington, United States, 98109
Contact: Nicole Bates 206-543-6620

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Lupe G. Salazar, MD

Tumor Vaccine Group at the University of Washington

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000489008, UWCC-UW-6193, UWCC-03-9836-D01, FHCRC-6193, FHCRC-UW-6193, FHCRC-119
Study First Received:	July 26, 2006
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00357448 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

ovarian clear cell cystadenocarcinoma
ovarian mixed epithelial carcinoma
ovarian mucinous cystadenocarcinoma
ovarian serous cystadenocarcinoma
ovarian undifferentiated adenocarcinoma
recurrent ovarian epithelial cancer

stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
ovarian endometrioid adenocarcinoma
fallopian tube cancer
peritoneal cavity cancer

Study placed in the following topic categories:

Cystadenocarcinoma, Serous
Fallopian Tube Cancer
Gonadal Disorders
Urogenital Neoplasms
Ovarian Diseases
Carcinoma, Endometrioid
Genital Diseases, Female
Peritoneal Diseases
Ovarian Cancer
Analgesics
Endocrine Gland Neoplasms
Ovarian Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases

Abdominal Neoplasms
Ovarian Epithelial Cancer
Recurrence
Fallopian Tube Neoplasms
Carcinoma
Digestive System Diseases
Analgesics, Non-Narcotic
Interleukin-2
Denileukin diftitox
Gastrointestinal Neoplasms
Peripheral Nervous System Agents
Peritoneal Neoplasms
Endocrinopathy
Adenocarcinoma

Additional relevant MeSH terms:

Gonadal Disorders
Antineoplastic Agents
Physiological Effects of Drugs
Urogenital Neoplasms
Ovarian Diseases
Genital Diseases, Female
Neoplasms by Site
Sensory System Agents
Therapeutic Uses
Peritoneal Diseases
Analgesics
Endocrine Gland Neoplasms
Ovarian Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female

Endocrine System Diseases
Abdominal Neoplasms
Fallopian Tube Neoplasms
Pharmacologic Actions
Adnexal Diseases
Fallopian Tube Diseases
Neoplasms
Digestive System Diseases
Interleukin-2
Analgesics, Non-Narcotic
Denileukin diftitox
Peripheral Nervous System Agents
Peritoneal Neoplasms
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 10, 2009