Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00466960

Purpose

RATIONALE: Colony stimulating factors, such as sargramostim (GM-CSF), may stimulate the immune system in different ways and stop tumor cells from growing and may also increase the number of immune cells found in bone marrow or peripheral blood and help the immune system recover from the side effects of chemotherapy. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving GM-CSF together with paclitaxel albumin-stabilized nanoparticle formulation may be an effective treatment for ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.

PURPOSE: This phase II trial is studying how well giving GM-CSF together with paclitaxel albumin-stabilized nanoparticle formulation works in treating patients with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that did not respond to previous chemotherapy

Condition	Intervention	Phase
Brenner Tumor Fallopian Tube Cancer Ovarian Clear Cell Cystadenocarcinoma Endometrioid Carcinoma Ovary Ovarian Mixed Epithelial Carcinoma Mucinous Cystadenocarcinoma of Ovary Serous Cystadenocarcinoma Ovary Ovarian Undifferentiated Adenocarcinoma Malignant Tumor of Peritoneum Ovarian Epithelial Cancer Recurrent Ovarian Epithelial Cancer Stage III Stage IV Ovarian Carcinoma	Biological: sargramostim Drug: paclitaxel albumin-stabilized nanoparticle formulation Other: laboratory biomarker analysis Other: immunologic technique	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Trial of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) With Weekly Protein Bound Paclitaxel (Abraxane™) as Chemoimmunotherapy for Platinum-Refractory/Resistant Epithelial Ovarian, Primary Peritoneal and Fallopian Tube Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Paclitaxel Granulocyte-macrophage colony-stimulating factor Sargramostim

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Time to progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Correlation between circulating monocytes and time to progression [ Time Frame: At day 1 of induction therapy, days 1-7 of maintenance therapy, 6 months after induction therapy, and at end of study ] [ Designated as safety issue: No ]
Correlation between circulating dendritic cell count and maturation state with clinical response and response duration [ Time Frame: At day 1 of induction therapy, days 1-7 of maintenance therapy, 6 months after induction therapy, and at end of study ] [ Designated as safety issue: No ]
Precursor frequency of circulating activated T lymphocytes against common ovarian cancer tumor associated antigens to measure the development of immunity to anti-tumor antigens [ Time Frame: During treatment with chemotherapy and GM-CSF ] [ Designated as safety issue: No ]
Precursor frequency of circulating T lymphocytes activated against foreign antigens [ Time Frame: At day 1 of induction therapy, days 1-7 of maintenance therapy, 6 months after induction therapy, and at end of study ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	May 2006
Estimated Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (colony stimulating factor and chemotherapy) INDUCTION THERAPY: Patients receive GM-CSF SC once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.	Biological: sargramostim Given SC Other Names: GM-CSF Leukine Prokine Drug: paclitaxel albumin-stabilized nanoparticle formulation Given IV Other Names: ABI-007 nab paclitaxel nab-paclitaxel nanoparticle albumin-bound paclitaxel Other: laboratory biomarker analysis Correlative studies Other: immunologic technique Correlative studies Other Names: immunological laboratory methods laboratory methods, immunological

Arms

Assigned Interventions

Experimental: Treatment (colony stimulating factor and chemotherapy)

INDUCTION THERAPY: Patients receive GM-CSF SC once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: sargramostim

Given SC

Other Names:

GM-CSF
Leukine
Prokine

Drug: paclitaxel albumin-stabilized nanoparticle formulation

Given IV

Other Names:

ABI-007
nab paclitaxel
nab-paclitaxel
nanoparticle albumin-bound paclitaxel

Other: laboratory biomarker analysis

Correlative studies

Other: immunologic technique

Correlative studies

Other Names:

immunological laboratory methods
laboratory methods, immunological

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine whether chronic GM-CSF administration during and after cytotoxic chemotherapy with paclitaxel albumin-stabilized nanoparticle formulation can induce a longer remission than experienced in the most recent platinum-containing regimen.

SECONDARY OBJECTIVES:

I. To determine the extent to which chronic GM-CSF administration can increase the number of activated monocytes in patients with advanced stage epithelial ovarian cancer.

II. To determine the extent to which chronic GM-CSF administration can increase the number and activation state of peripheral circulating antigen presenting cells, such as dendritic cells and activated monocytes, in patients with advanced epithelial ovarian cancer.

III. To determine the extent to which chronic GM-CSF administration can increase the number and functional status of T cells that recognize tumor specific antigens in patients with advanced stage epithelial ovarian cancer.

IV. To determine the extent to which chronic GM-CSF administration can increase the number and functional status of antigen specific T cells that recognize foreign pathogens in patients with advanced stage epithelial ovarian cancer.

OUTLINE:

INDUCTION THERAPY: Patients receive GM-CSF subcutaneously (SC) once daily on days 16-26. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 14 days after last GM-CSF injection, patients receive GM-CSF SC once daily on days 1-15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for 6 months and then every 3 months thereafter.

Eligibility

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

Criteria

Inclusion Criteria:

Patients must have histologically proven epithelial ovarian, fallopian tube or primary peritoneal malignancies, excluding tumors of low malignant potential (borderline)
Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified
Patients must have either primary platinum refractory or resistant carcinoma or secondary platinum resistant disease:
1. Primary platinum refractory disease is defined as progression of disease on initial platinum-based chemotherapy or persistent disease at the conclusion of the initial platinum-based chemotherapy course associated with the primary debulking surgery.
2. Primary platinum resistant disease is defined as recurrence of carcinoma within 6 months (+ 14 days) of completion of initial platinum-based chemotherapy associated with the primary debulking surgery. (The 14 day window is to allow study entry for those patients where evidence clearly suggests that had an assessment been made early the patient would have met the 6 month time line. This will be determined by the study principal investigator [P.I.])
3. Secondary platinum resistant disease is defined as meeting any one of the listed criteria during or following a subsequent platinum containing regimen.
Patients must have an elevated serum cancer antigen (CA)125 on two occasions greater than 7 days apart
Absolute neutrophil count >= 1500/uL
Platelets >= 100,000/uL
Creatinine =< 2.0 mg/dL
Total bilirubin =< 1.5 mg/dL (unless history of Gilbert's disease)
Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x upper limit of normal (ULN) or < 5 x ULN with documented report of hepatic metastases
Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; at least three weeks must have elapsed since prior chemotherapy or radiation therapy

Exclusion Criteria:

Patient has an allergic history to paclitaxel or GM-CSF, not manageable by pre-medication and/or slow drug infusion
Patient has poorly controlled arrhythmias or unstable coronary artery disease or has had a myocardial infarction within the last six months
Patient with active pulmonary edema or pleural effusion
Active infection requiring IV antibiotics
Patient currently requires lithium, (due to drug interaction with GM-CSF [Leukine])
Patient currently presents with a neurotoxicity > Grade 1
Women of childbearing potential
Patients with a history of other invasive malignancies, within the previous 5 years are excluded, with the exception of non-melanoma skin cancer

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00466960

Locations

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Barbara Goff

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

More Information

No publications provided

Responsible Party:	Goff, Barbara, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:	NCT00466960 History of Changes
Other Study ID Numbers:	6168, NCI-2010-00556
Study First Received:	April 25, 2007
Last Updated:	April 1, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Adenocarcinoma
Brenner Tumor
Neoplasms
Carcinoma
Cystadenocarcinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Cystadenocarcinoma, Mucinous
Cystadenocarcinoma, Serous
Neoplasms by Histologic Type
Neoplasms, Fibroepithelial
Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Gonadal Disorders
Endocrine System Diseases
Neoplasms, Cystic, Mucinous, and Serous
Endocrine Gland Neoplasms
Neoplasms by Site
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on February 02, 2012