Brief Title
Chemoimmunotherapy Study for Patients With Epithelial Ovarian Cancer
Official Title
A Phase II Study of Chemoimmunotherapy for Patients With Potentially Platinum Sensitive Müllerian (Epithelial Ovarian, Peritoneal, or Fallopian Tube) Carcinomas
Brief Summary
Primary Objectives:
1. Determine response rate, time to progression, and toxicity of a schedule of carboplatin
by IV (intravenous) infusion, GM-CSF and rIFN-g by SC (subcutaneous injection) in
patients with potentially platinum-sensitive recurrent Müllerian carcinomas.
2. Determine whether this treatment schedule is associated with:
1. increased levels of monocytes (>2-fold and absolute numbers 1000 cells/ml,) and of
LN-DR+ DC (CD11c+ and CD123+ subsets)
2. induction of priming and activation of MO/MA (monocytes/ macrophages), and
maturation of DC (dendritic cells).
3. Determine the toxicity profile of consolidation treatment with IP (intraperitoneal)
injections of rIFN-g added to carboplatin (IV) and GM-CSF (SC) for 4 doses/course.
4. Determine the effects of carboplatin plus GM-CSF and rIFN-g on quality of life in
patients with platinum-sensitive Müllerian carcinomas.
5. To begin an exploration of cell surface proteins on purified activated peripheral blood
and ascites monocyte/macrophages both before and after treatment with GM-CSFand rIFN-g.
Detailed Description
Carboplatin is a chemotherapy drug that is used for the treatment of ovarian cancer. GM-CSF
is a protein that is used to increase the production of white blood cells. rIFN-g is a
protein that stimulates cells of the immune system.
Participants will need to have pre-study blood work (about 4 teaspoons) as part of their
evaluation for study entry. In addition, a chest x-ray and CT scan of the abdomen and pelvis
will need to be done before any treatments.
Participants in this study will receive a frequently used dose of carboplatin by vein over 1
hour every 28 days. In addition, GM-CSF will be given for 7 days and rIFN-g will be given for
2 days before and after chemotherapy. Both drugs will be given as injections under the skin.
They will be repeated with each chemotherapy course that participants receive.
GM-CSF and rIFN-g are being used to try to stimulate the immune system in the belief that
this adds to the effectiveness of the chemotherapy on the tumor. During each course of
chemotherapy treatment, blood samples will be taken in order to evaluate the blood count
response to GM-CSF. Participants will need to remain in the Houston area beginning with the
first injection of GM-CSF and for up to 9 days following the carboplatin infusion for the
first course.
QOL forms will be completed at 5 separate time points during the first course of
chemotherapy. Later courses will only have 2 time points for completion of the QOL forms. The
completion of these forms will help researchers to evaluate the effects of the carboplatin
and the 2 proteins on participants and their quality of life.
Participants will receive 3 courses of treatment (each course will include 1 treatment with
carboplatin followed by 2 separate treatment cycles with GM-CSF and rIFN-g) and then be
evaluated for tumor response. If the tumor is responding, 3 additional courses will be given.
If after 6 courses of treatment, the tumor has completely responded and there is no evidence
of the disease, then up to 4 additional courses can be given for completion of therapy. If
the tumor is still responding after 6 courses but has not completely gone away, then
additional courses can be given as long as the tumor is responding before completion therapy
can be considered.
Completion therapy will include carboplatin given every 28 days by vein along with injections
of GM-CSF under the skin before and after the chemotherapy. Injections of rIFN-g will be
given directly into the abdomen through an abdominal catheter if possible. If this is not
possible, then the rIFN-g will be given as injections under the skin. Participants may choose
not to receive the rIFN-g through a catheter during the completion phase and can continue to
receive it under the skin with the chemotherapy. A maximum of 4 additional courses can be
given during this phase of the study.
Participants whose disease gets worse will be taken off the study. Participants who have
intolerable side effect from the study drugs will also be taken off the study treatment.
Participants will have follow up CT scans after every 3 courses of treatment. Following
completion of all treatments, participants will need to return to M. D. Anderson every 3
months for follow-up exams. This will include a physical exam, blood work, and a CT scan.
This is an investigational study. A total of 65 patients will take part in this study.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Patients With Response
Condition
Ovarian Cancer
Intervention
Carboplatin
Study Arms / Comparison Groups
Chemoimmunotherapy
Description: GM-CSF Starting dose of 400 mg injected under the skin once a day for 7 days prior to and following each course of chemotherapy + rIFN-g (Interferon Gamma) 0.1 mg injected under the skin for 2 days before and after chemotherapy (Day 5 and Day 7 of each 7-day GM-CSF cycle) + Paraplatin (Carboplatin) AUC of 5 by 1 hour IV infusion every 28 days
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
59
Start Date
January 2003
Completion Date
January 2009
Primary Completion Date
January 2009
Eligibility Criteria
Inclusion Criteria:
1. Patients with Müllerian carcinomas (primary epithelial ovarian, primary peritoneal, or
fallopian tube) who have had a response to platinum-based chemotherapy and have a
chemotherapy treatment-free interval of at least 6 months. These patients are
designated potentially platinum-sensitive.
2. Measurable disease by radiological or clinical examination parameters.
3. No prior immunotherapy.
4. No concurrent steroids or radiation therapy.
5. Adequate hematological parameters (ANC >/= 1500 cells/UL, platelets >/= 100,000
cells/UL
6. Adequate renal function (serum creatinine 10% over 4 months
5. Radiation therapy to whole abdomen
6. History of clinical or EKG findings suggestive of active (within the last 6 months)
heart disease
7. Patients with active autoimmune or inflammatory bowel disease
8. Patients with an active serious infection or other serious underlying medical
condition that would otherwise impair their ability to receive protocol treatment.
9. Dementia or significantly altered mental status that would prohibit the understanding
and/or giving of informed consent.
10. Patients with prior hypersensitivity to platinum agents
11. Patients with history of other malignancy, with the exception of non-melanomatous skin
cancer; unless in complete remission and off therapy for a minimum of 5 years.
Gender
Female
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Ralph Freedman, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00501644
Organization ID
ID02-231
Responsible Party
Sponsor
Study Sponsor
M.D. Anderson Cancer Center
Collaborators
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Study Sponsor
Ralph Freedman, MD, PhD, Principal Investigator, M.D. Anderson Cancer Center
Verification Date
August 2012