Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00977574
First received: September 12, 2009
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This randomized phase II trial is studying giving paclitaxel and carboplatin together with bevacizumab to see how well it works compared with giving paclitaxel and carboplatin together with temsirolimus or giving ixabepilone and carboplatin together with bevacizumab in treating patients with stage III, stage IV, or recurrent endometrial cancer. Drugs used in chemotherapy, such as paclitaxel, carboplatin, and ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which treatment regimen is most effective in treating patients with endometrial cancer.


Condition Intervention Phase
Endometrial Adenocarcinoma
Endometrial Adenosquamous Cell Carcinoma
Endometrial Clear Cell Carcinoma
Recurrent Endometrial Carcinoma
Stage III Endometrial Carcinoma
Stage IV Endometrial Carcinoma
Drug: paclitaxel
Drug: carboplatin
Biological: bevacizumab
Drug: temsirolimus
Drug: ixabepilone
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Three Arm Randomized Phase II Study of Paclitaxel/Carboplatin/Bevacizumab (NSC#704865), Paclitaxel/Carboplatin/Temsirolimus (NSC#683864 ) and Ixabepilone (NSC#710428) / Carboplatin/Bevacizumab as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Best confirmed response assessed by RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: September 2009
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (paclitaxel, carboplatin, bevacizumab)
Patients receive paclitaxel IV over 3 hours, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (paclitaxel, carboplatin, temsirolimus)
Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (ixabepilone, carboplatin, bevacizumab)
Patients receive ixabepilone IV over 1 hour, carboplatin IV over 30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed endometrial carcinoma, including any of the following epithelial cell types:

    • Endometrioid adenocarcinoma
    • Serous adenocarcinoma
    • Undifferentiated carcinoma
    • Clear cell adenocarcinoma
    • Mixed epithelial carcinoma
    • Adenocarcinoma not otherwise specified
    • Mucinous adenocarcinoma
    • Squamous cell carcinoma
    • Transitional cell carcinoma
  • Stage III, IVA-B, or recurrent disease
  • Refractory to curative or established therapy
  • Measurable disease*, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by chest x-ray or ≥ 10 mm by CT scan, MRI, or caliper measurement by clinical exam
  • Lymph nodes must be ≥ 15 mm in short axis by CT scan or MRI
  • No history or evidence of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or any brain metastases
  • Not eligible for a higher priority GOG protocol (any active GOG phase III protocol or rare tumor protocol), if one exists
  • GOG performance status 0-2
  • ANC ≥ 1,500/mm³
  • Platelets ≥ 100,000/mm³
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • SGOT and SGPT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Urine protein:creatinine ratio < 1.0 g OR < 1,000 mg by 24-hour urine collection
  • INR and PTT ≤ 1.5 times ULN
  • Fasting cholesterol < 300 mg/dL
  • Fasting triglycerides ≤ 2.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • No other invasive malignancies within the past 3 years, except nonmelanoma skin cancer
  • No serious, non-healing wound, ulcer, or bone fracture, including history of abdominal/pelvic fistula, gastrointestinal perforation, or intraabdominal abscess within the past 3 months

    • No uncorrected underlying lesions that caused the fistula or perforation
  • No active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
    • Myocardial infarction or unstable angina within the past 6 months
    • NYHA class II-IV congestive heart failure
    • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), or cardiac arrhythmias requiring anti-arrhythmic medications

      • Atrial fibrillation that is well controlled with anti-arrhythmic medication allowed
    • Peripheral vascular disease ≥ CTCAE grade 2
    • History of cerebrovascular accident (stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
    • Aortic aneurysm and/or history of aortic dissection
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No significant traumatic injury within the past 28 days
  • No known history of interstitial pneumonitis
  • No hypoxemia ≥ grade 2 by CTCAE v.3
  • No dyspnea ≥ grade 2 by CTCAE v.3
  • No uncontrolled diabetes or baseline hemoglobin A1C > 8%
  • No peripheral neuropathy > grade 1 by CTCAE v.3
  • At least 4 weeks since prior radiation therapy (RT) for treatment of endometrial carcinoma allowed, including pelvic RT, extended field pelvic/para-aortic RT, and/or intravaginal brachytherapy

    • More than 3 years since prior RT to any portion of the abdominal cavity or pelvis, other than for the treatment of endometrial cancer
    • More than 3 years since prior RT for localized cancer of the breast, head and neck, or skin and no metastatic or recurrent disease
  • At least 1 week since prior hormonal therapy for treatment of endometrial carcinoma
  • More than 28 days since prior and no concurrent major surgical procedure or open biopsy
  • More than 7 days since prior minor surgical procedures, fine-needle aspirates, or core biopsies
  • No prior chemotherapy or target therapy (e.g., bevacizumab or other VEGF pathway targeted therapy, temsirolimus, everolimus, ridaforolimus, sirolimus, or any other PI3K/AKT/mTor pathway targeted therapy), including chemotherapy used for radiation sensitization, for treatment of endometrial carcinoma

    • More than 3 years since prior chemotherapy for any abdominal or pelvic tumor
    • More than 3 years since prior adjuvant chemotherapy for localized breast cancer and no metastatic or recurrent disease
  • No prior cancer treatment that contraindicates this protocol therapy
  • No concurrent treatment with potent CYP3A4 inhibitors and agents that have CYP3A4 induction potential (arms II and III)
  • No concurrent sunitinib malate during temsirolimus treatment (arm II)
  • No concurrent amifostine or other protective agents
  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: NCT00977574

  Show 235 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Carol Aghajanian Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00977574     History of Changes
Other Study ID Numbers: NCI-2011-01969, NCI-2011-01969, CDR0000654472, GOG-0086P, GOG-0086P, GOG-0086P, U10CA027469
Study First Received: September 12, 2009
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Endometrial Neoplasms
Carcinoma, Adenosquamous
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Antibodies
Antibodies, Monoclonal
Sirolimus
Everolimus
Epothilone B
Bevacizumab
Carboplatin
Paclitaxel
Epothilones
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014