Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Chemoimmunotherapy Study for Patients With Epithelial Ovarian Cancer

This study has been completed.
Sponsor:
Collaborators:
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Bristol-Myers Squibb
InterMune
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00501644
First received: July 12, 2007
Last updated: August 1, 2012
Last verified: August 2012
  Purpose

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.

Condition Intervention Phase
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Drug: Carboplatin
Drug: GM-CSF (Sargramostim)
Drug: Interferon Gamma
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Chemoimmunotherapy for Patients With Potentially Platinum Sensitive Müllerian (Epithelial Ovarian, Peritoneal, or Fallopian Tube) Carcinomas

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patients With Response [ Time Frame: Follow up CT scans after every 3 courses of treatment and following completion of all treatments. ] [ Designated as safety issue: No ]
    Per World Health Organization (WHO) Tumor Response: Complete Response (CR), Partial Response (PR) or Progressive Disease (PD). CR defined as disappearance of all target lesions, PR as > = 30% decrease in sum of longest dimensions of target lesions with reference baseline sum longest dimensions and if CA 125 levels declined by >50%, provided target lesion size did not increase by >20% on imaging, and PD as >20% increase in sum of longest dimensions of target lesions taking as references smallest sum of longest dimensions recorded since treatment started, or appearance of 1 or > new lesions.


Enrollment: 59
Study Start Date: January 2003
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemoimmunotherapy
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
Drug: Carboplatin
AUC of 5 by 1 hour IV infusion every 28 days.
Other Name: Paraplatin
Drug: GM-CSF (Sargramostim)
Starting dose of 400 mg injected under the skin once a day for 7 days prior to and following each course of chemotherapy.
Other Name: Sargramostim
Drug: 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).
Other Name: 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 </= 1.5 mg/dl)
  7. Adequate hepatic function (serum bilirubin </= 1.5 mg/dl)
  8. SGOT or SGPT </= 2.5 normal
  9. Zubrod status </= 2
  10. Signed informed consent
  11. Patients with no more than 2 prior therapy regimens (1st line platinum and platinum reinduction will count as one)

Exclusion Criteria:

  1. Pregnant or lactating women
  2. Patients with brain metastases
  3. Serum albumin <3 gm/dl
  4. Weight loss >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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00501644

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Bristol-Myers Squibb
InterMune
Investigators
Principal Investigator: Ralph Freedman, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00501644     History of Changes
Other Study ID Numbers: ID02-231
Study First Received: July 12, 2007
Results First Received: December 23, 2010
Last Updated: August 1, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Carboplatin
Interferon-gamma
Interferons
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014