| Study Summary: |
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OBJECTIVES:
Primary
- To estimate the proportion of patients with persistent or recurrent endometrial cancer,
who survive progression-free for at least 6 months and the proportion of patients who
have objective tumor response (complete or partial), treated with angiopoietin
1/2-neutralizing peptibody AMG 386 (AMG 386).
- To assess the frequency of objective tumor response in patients treated with this
regimen.
- To determine the nature and degree of toxicity of this regimen in these patients.
Secondary
- To determine the duration of progression-free survival and overall survival of patients
treated with this regimen.
OUTLINE: This is a multicenter study.
Patients receive angiopoietin 1/2-neutralizing peptibody AMG 386 IV over 30-60 minutes on
days 1, 8, 15, and 21. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.
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| Criteria: |
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DISEASE CHARACTERISTICS:
- Histologically confirmed endometrial carcinoma
- Recurrent or persistent disease
- Histologic confirmation of the original primary tumor is required
- Histologic or cytologic confirmation of the recurrent/progressive disease
is desired but not required
- Disease refractory to curative therapy or established treatments
- The following epithelial cell types are eligible:
- Endometrioid adenocarcinoma
- Serous adenocarcinoma
- Undifferentiated carcinoma
- Clear cell adenocarcinoma
- Mixed epithelial carcinoma
- Adenocarcinoma not otherwise specified (N.O.S.)
- Mucinous adenocarcinoma
- Squamous cell carcinoma
- Transitional cell carcinoma
- Must have measurable disease, defined as ≥ 1 lesion that can be accurately measured
in ≥ 1 dimension (longest diameter to be recorded) as ≥ 10 mm by CT scan, MRI, or
caliper by clinical exam OR ≥ 20 mm by chest x-ray
- Lymph nodes must be ≥ 15 mm in short axis when measured by CT scan or MRI
- Must have ≥ 1 target lesion to assess response as defined by RECIST
- Tumors within a previously irradiated field will be designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence ≥ 90 days following completion of radiation therapy
- Patients must not be eligible for a higher priority GOG protocol, if one exists
(e.g., any active GOG Phase III or Rare Tumor protocol for the same patient
population)
- Must have had 1 prior chemotherapy regimen for management of endometrial carcinoma
- Chemotherapy administered in conjunction with primary radiation as a
radio-sensitizer is counted as a chemotherapy regimen
- No history or evidence of CNS disease, including brain tumor or brain metastases,
upon physical examination
PATIENT CHARACTERISTICS:
- GOG performance status (PS) 0-2 (for patients who received 1 prior chemotherapy
regimen) OR GOG PS 0-1 (for patients who received 2 prior chemotherapy regimens)
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9.0 g/dL
- Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 60
mL/min
- Bilirubin ≤ 1.5 times ULN
- AST and ALT ≤ 3.0 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- INR ≤ 1.5 times ULN (or an in-range INR between 2 and 3 for patient on a stable dose
of therapeutic warfarin)
- PTT ≤ 1.5 times ULN
- Albumin ≥ 2.8 mg/dL
- Urine protein: proteinuria ≤ 1 on dipstick OR < 1 g by 24-hour urine collection
- Free of active infection requiring antibiotics except for uncomplicated UTI
- Peripheral neuropathy (sensory or motor) ≤ grade 1
- Fertile patients must agree to use effective non-hormonal double-barrier
contraception methods (e.g., condom plus diaphragm) from the time of signing the
informed consent through 6 months after the last dose of study drug
- Not pregnant or nursing
- Negative pregnancy test
- More than 3 years since other invasive malignancies except non-melanoma skin cancer
and other specific malignancies (e.g., localized breast, head and neck , or skin
cancer for which the patient remains free of recurrence or metastatic disease)
- No symptoms of partial or complete bowel obstruction, including any of the following:
- Fistula within the past 6 months
- Intra-abdominal abscess or bowel perforation
- Patients requiring total parenteral nutrition or parenteral hydration
- No uncontrolled seizures with standard medical therapy
- No clinically significant cardiovascular disease including, but not limited to, any
of the following:
- Myocardial infarction or unstable angina within the past 12 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 (except for atrial fibrillation that is well controlled with
anti-arrhythmic medication)
- Peripheral vascular disease ≥ grade 2
- Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or
subarachnoid hemorrhage within the past 6 months
- History of arterial ischemia or thrombus
- No uncontrolled hypertension (systolic blood pressure (BP) > 150 mm Hg or diastolic
BP > 90 mm Hg)
- Anti-hypertensive medications to control hypertension allowed
- No serious non-healing wound, ulcer (including gastrointestinal), or bone fracture
- No known HIV, hepatitis C, or chronic or active hepatitis B infection
- No patient with any condition that, in the investigator's opinion, makes the patient
unsuitable for study participation
- No known sensitivity to any of the products to be administered during study
- No history of allergic reactions to bacterially produced proteins
- No significant traumatic injury within the past 28 days
- No significant bleeding within 6 months of enrollment or pathologic conditions that
carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor
involving major vessels
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from recent surgery, radiotherapy, or chemotherapy
- At least 1 week since any prior hormonal therapy directed at the malignant tumor
- Any other prior therapy directed at the malignant tumor, including chemotherapy and
immunologic agents, must be discontinued at least 3 weeks prior to registration
- Any prior radiation therapy must be completed at least 4 weeks prior to registration
- One prior cytotoxic regimen for management of recurrent or persistent disease allowed
- More than 28 days since prior major surgical procedure or open biopsy
- No anticipation of major surgical procedure during course of the study
- More than 7 days since prior minor surgical procedures
- Paracentesis and thoracentesis allowed at the discretion of the investigator and
as clinically indicated
- More than 30 days since prior immune modulators (e.g., systemic cyclosporine or
tacrolimus)
- No prior radiotherapy to any portion of the abdominal cavity or pelvis within the
past 3 years except for treatment of endometrial cancer
- Prior radiotherapy for localized cancer of the breast, head and neck, or skin
allowed, provided it was completed > 3 years ago and patient remains free of
recurrence or metastatic disease
- No prior chemotherapy for any portion of the abdominal cavity or pelvis within the
past 3 years except for treatment of endometrial cancer
- Prior adjuvant chemotherapy for localized breast cancer allowed, provided it was
completed > 3 years ago and patient remains free of recurrence of metastatic
disease
- Patients must have NOT received any non-cytotoxic (biologic or targeted) agents as
part of their primary treatment or for management of recurrent or persistent disease
- Non-cytotoxic (biologic or targeted) agents include (but are not limited to)
monoclonal antibodies, cytokines, and small-molecule inhibitors of signal
transduction
- Prior hormonal therapy is allowed; there is no limit on the number of prior
hormonal therapies allowed
- No prior or other concurrent angiopoietin 1/2-neutralizing peptibody AMG 386, other
molecules that inhibit the angiopoietins, or Tie2 receptor
- No prior cancer treatment that contraindicates this protocol therapy
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