A Trial of Intravenous Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2A in Stage III or IV Ovarian Cancer
Primary Purpose
Epithelial Ovarian Cancer, Extraovarian Peritoneal Cancer, Fallopian Tube Carcinoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Denileukin Diftitox/SC Pegylated IFNα-2a
Sponsored by
About this trial
This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring Epithelial Ovarian Cancer, FIGO (Int Federation of Gyn and Ob )Stage III or Stage IV, Extraovarian Peritoneal Cancer, Fallopian Tube Carcinoma Failing
Eligibility Criteria
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
Sites / Locations
- CTRC (Cancer Therapy and Research Center) at UTHSCSA
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Denileukin Diftitox/SC Pegylated IFNα-2A
Arm Description
Administration of Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2A
Outcomes
Primary Outcome Measures
Clinical Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Response = CR + PR.
Failure to respond criteria are not based on RECIST criteria, which have unclear application to immune-based clinical trials. Instead, novel lack-of-failure criteria, rather than failure-of-success criteria have been written to avoid stopping therapy prematurely without compromising patient safety, to accommodate the uncertainties of assessing failure in this setting. The criteria as written are based on sound medical, scientific and ethical principles. The trial is further designed to help establish the utility of these novel criteria.
Secondary Outcome Measures
Full Information
NCT ID
NCT01773889
First Posted
January 14, 2013
Last Updated
March 13, 2018
Sponsor
The University of Texas Health Science Center at San Antonio
1. Study Identification
Unique Protocol Identification Number
NCT01773889
Brief Title
A Trial of Intravenous Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2A in Stage III or IV Ovarian Cancer
Official Title
A Phase II Trial of Intravenous Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2a to Treat Epithelial Ovarian Cancer FIGO Stage III or Stage IV, Extraovarian Peritoneal or Fallopian Tube Carcinoma or Ineligible for First-Line Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Terminated
Why Stopped
Lack of funding
Study Start Date
June 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
June 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Ovarian Cancer, Extraovarian Peritoneal Cancer, Fallopian Tube Carcinoma
Keywords
Epithelial Ovarian Cancer, FIGO (Int Federation of Gyn and Ob )Stage III or Stage IV, Extraovarian Peritoneal Cancer, Fallopian Tube Carcinoma Failing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Denileukin Diftitox/SC Pegylated IFNα-2A
Arm Type
Experimental
Arm Description
Administration of Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2A
Intervention Type
Drug
Intervention Name(s)
Denileukin Diftitox/SC Pegylated IFNα-2a
Other Intervention Name(s)
Ontak plus Pegylated IFNα-2a
Primary Outcome Measure Information:
Title
Clinical Response Rate
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Response = CR + PR.
Failure to respond criteria are not based on RECIST criteria, which have unclear application to immune-based clinical trials. Instead, novel lack-of-failure criteria, rather than failure-of-success criteria have been written to avoid stopping therapy prematurely without compromising patient safety, to accommodate the uncertainties of assessing failure in this setting. The criteria as written are based on sound medical, scientific and ethical principles. The trial is further designed to help establish the utility of these novel criteria.
Time Frame
every 3 months until the date of first documented progression or date of death from any cause, assessed up to 2 years when study terminated early
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tyler Curiel, MD
Organizational Affiliation
The University of Texas Health Science Center at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
CTRC (Cancer Therapy and Research Center) at UTHSCSA
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Trial of Intravenous Denileukin Diftitox Plus Subcutaneous Pegylated IFNα-2A in Stage III or IV Ovarian Cancer
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