Clinical trial NCT00501644
Conditions: Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer
Keywords: Müllerian Carcinomas Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer Epithelial Ovarian Peritoneal Fallopian Tube Chemoimmunotherapy Platinum Sensitive Müllerian Carboplatin Paraplatin GM-CSF Sargramostim Interferon Gamma Quality of Life QOL
Sponsor: M.D. Anderson Cancer Center
Start date: 2003-01-01; Completion date: 2009-01-01
Enrollment: 59 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: 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
Interventions: intervention 1: Carboplatin intervention 2: GM-CSF (Sargramostim) intervention 3: Interferon Gamma
Intervention descriptions: intervention 1: AUC of 5 by 1 hour IV infusion every 28 days. intervention 2: Starting dose of 400 mg injected under the skin once a day for 7 days prior to and following each course of chemotherapy. intervention 3: 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).

Protocol documents: