Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01005329
First received: October 29, 2009
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

This phase II trial is studying the side effects of giving intensity-modulated radiation therapy together with cisplatin and bevacizumab followed by carboplatin and cisplatin and to see how well it works in treating patients who have undergone surgery for high-risk endometrial cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, 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 blood flow to the tumor. Giving intensity-modulated radiation therapy together with chemotherapy and bevacizumab after surgery may kill any tumor cells that remain after surgery.


Condition Intervention Phase
Endometrial Adenocarcinoma
Endometrial Adenosquamous Cell Carcinoma
Endometrial Clear Cell Carcinoma
Endometrial Papillary Serous Carcinoma
Stage I Endometrial Carcinoma
Stage II Endometrial Carcinoma
Stage III Endometrial Carcinoma
Stage IV Endometrial Carcinoma
Radiation: intensity-modulated radiation therapy
Drug: cisplatin
Biological: bevacizumab
Drug: carboplatin
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Postoperative Intensity Modulated Radiation Therapy (IMRT) With Concurrent Cisplatin and Bevacizumab Followed by Carboplatin and Paclitaxel for Patients With Endometrial Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Treatment-related, Grade 3+, Non-hematologic Adverse Events as Assessed by NCI CTCAE (Common Terminology Criteria for Adverse Events) v4.0 [ Time Frame: From start of treatment to 90 days ] [ Designated as safety issue: Yes ]
    The rate of the acute specified AEs (adverse events) from previous trial RTOG 9708 (RT + cisplatin) was 44% and the hypothesis is that the addition of bevacizumab to IMRT + cisplatin will not increase this rate beyond 60%. This study was designed with a 1-sided, upper bound confidence interval to estimate this AE rate. Twenty-seven evaluable patients were required to have 95% confidence that the true grade 3+ non-hematologic treatment-related AE rate is not greater than 60%. Please note that this is a 95% ONE-SIDED confidence bound which is equivalent to the upper bound of a two-sided 90% confidence interval.


Secondary Outcome Measures:
  • Treatment-related, Grade 3+, Non-hematologic Adverse Events as Assessed by NCI CTCAE v4.0 [ Time Frame: From start of treatment to one year ] [ Designated as safety issue: Yes ]
  • All Treatment-related Adverse Events as Assessed by NCI CTCAE v4.0 [ Time Frame: From start of treatment to end of follow-up ] [ Designated as safety issue: Yes ]
  • Overall Survival [ Time Frame: From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.

  • Disease-free Survival [ Time Frame: From registration to date of first failure or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method.

  • Pelvic Failure [ Time Frame: From registration to date of pelvic failure or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ] [ Designated as safety issue: No ]
    Will be estimated using the cumulative incidence method.

  • Distant Failure [ Time Frame: From registration to date of distant failure or last follow-up. Analysis occurs after all patients have been potentially followed for one year. ] [ Designated as safety issue: No ]
    Will be estimated using the cumulative incidence method.


Enrollment: 34
Study Start Date: November 2009
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients undergo pelvic intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Radiation: intensity-modulated radiation therapy
Other Name: IMRT
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Detailed Description:

PRIMARY OBJECTIVE:

I. To assess the treatment-related, grade 3+, non-hematologic adverse-event rate within 90 days from the start of treatment with concurrent intensity-modulated radiotherapy, cisplatin, and bevacizumab followed by carboplatin and paclitaxel in patients with high-risk endometrial cancer.

SECONDARY OBJECTIVES:

I. To evaluate treatment-related adverse events occurring within 1 year from the start of treatment.

II. To evaluate all treatment-related adverse events. III. To evaluate disease-free and overall survival. IV. To evaluate local, regional, and distant failure.

OUTLINE: This is a multicenter study.

Patients undergo pelvic intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for 5 weeks. Patients may also undergo optional nodal boost radiotherapy and/or vaginal brachytherapy boost. Patients also receive concurrent cisplatin IV over 1 hour on days 1 and 29 and bevacizumab IV over 30-90 minutes on days 1, 15, and 29. Beginning 4-6 weeks after completing IMRT, cisplatin, and bevacizumab, patients receive carboplatin IV over 1 hour and paclitaxel IV over 3 hours on day 1. Treatment with carboplatin and paclitaxel repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed endometrial cancer, including 1 of the following cellular types:

    • Endometrioid endometrial adenocarcinoma
    • Clear cell carcinoma
    • Papillary serous adenocarcinoma
    • Adenosquamous cell carcinoma
    • Other adenocarcinoma variant
  • No carcinosarcoma
  • Meets 1 of the following criteria:

    • Grade 3 carcinoma with > 50% myometrial invasion (all papillary serous or clear cell carcinoma will be considered grade 3)
    • Grade 2 or 3 carcinoma with any cervical stromal invasion
    • Known extra-uterine disease confined to the pelvis, any grade
  • Patients must have undergone CT scan or PET/CT scan of the abdomen and pelvis within the past 56 days
  • Patients must have a chest x-ray or chest CT or PET-CT within the past 56 days
  • Has undergone hysterectomy (i.e., total abdominal, vaginal, robotic-assisted, radical, or laparoscopic-assisted vaginal hysterectomy) and bilateral salpingo-oophorectomy within the past 56 days
  • No positive common iliac or positive para-aortic nodal disease (defined as lymph nodes ≥ 2 cm in any dimension on CT scan or biopsy)
  • No evidence of metastatic extrauterine disease, gross or residual disease (not including pelvic nodal disease), or distant metastases
  • Zubrod performance status 0-1
  • ANC (Absolute Neutrophil Count) ≥ 1,500/mm^3 (without growth factor support)
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST (aspartate aminotransferase) and ALT (alanine amino transferase) ≤ 2 times ULN
  • Serum creatinine ≤ 1.5 mg/dL
  • Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg on 24-hour urine collection
  • INR (international normalized ratio) < 1.5 (for patients treated with warfarin within the past 14 days)
  • Not nursing
  • No neuropathy ≥ CTCAE (Common Terminology Criteria for Adverse Events) grade 1
  • No ototoxicity > CTCAE grade 2
  • No serious, active comorbidity, including any of the following:

    • Unstable angina and/or NYHA *New York Heart Association) class II-IV congestive heart failure requiring hospitalization within the past 12 months
    • Transmural myocardial infarction within the past 12 months
    • Acute bacterial or fungal infection requiring IV antibiotics
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS based upon current CDC (Centers for Disease Control) definition (HIV testing is not required)
    • Active gastrointestinal (GI) ulcers, GI bleeding, inflammatory bowel disease, or GI obstruction
    • Inadequately controlled hypertension, defined as systolic BP > 150 mm Hg and/or diastolic BP (blood pressure) > 90 mm Hg on antihypertensive medications
    • Significant vascular disease, including aortic aneurysm, aortic dissection, or arteriovenous malformation within the past 12 months
    • Serious cardiac arrhythmia on medication (well-controlled atrial fibrillation on medication allowed)
    • Serious non-healing wound, ulcer, or bone fracture
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No stroke/cerebrovascular event within the past 12 months
  • No arterial thromboembolic events, including transient ischemic attack or clinically symptomatic peripheral artery disease within the past 12 months
  • No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 6 months
  • No other invasive malignancies within the past 3 years other than nonmelanomatous skin cancer
  • No significant trauma within the past 28 days
  • No mental status changes or bladder problems that would preclude the ability to comply with bladder-filling instructions
  • No mental or psychiatric illness that would preclude giving informed consent
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No prior allergic reaction to bevacizumab, cisplatin, carboplatin, or paclitaxel
  • No concurrent erythropoietin, St. John's wort, therapeutic anticoagulants, aminoglycoside antibiotics, or amifostine
  • No prior organ transplantation
  • No prior external-beam radiotherapy to the pelvis resulting in overlapping of radiotherapy fields
  • No prior systemic chemotherapy for uterine cancer

    • Prior chemotherapy for a different cancer is allowed
  • No prior therapy with anti-VEGF (vascular endothelial growth factor compounds)
  • More than 28 days since prior major surgical procedure requiring open biopsy incision
  • No concurrent surgery (except for vascular access device placement or procedures that do not require significant incision)
  • No concurrent warfarin at doses > 1 mg/day

    • Concurrent prophylactic low molecular weight heparin allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01005329

  Show 37 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Akila Viswanathan Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01005329     History of Changes
Other Study ID Numbers: NCI-2011-01982, NCI-2011-01982, CDR0000657979, RTOG-0921, RTOG 0921, RTOG-0921, U10CA021661
Study First Received: October 29, 2009
Results First Received: January 8, 2014
Last Updated: January 8, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Endometrial Neoplasms
Carcinoma, Adenosquamous
Adenocarcinoma, Clear Cell
Adenomyoepithelioma
Cystadenocarcinoma, Serous
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
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Antibodies
Antibodies, Monoclonal
Bevacizumab
Cisplatin
Carboplatin
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014