MDACC Study Summary GOG 0229F

Study Summary
No. GOG 0229F:.......Endometrial......Robert Coleman......Gynecologic Oncology

Study Summary Title



Study Summary Number:	GOG 0229F

Study Title:	A Phase II Evaluation of VEGF-Trap (Aflibercept, NSC #724770, IND #BB100137, NCI-Supplied Agent) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Physician

New Patient Referral



Name:	Robert Coleman	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Gynecologic Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-745-3357 Contact us about clinical trials

General Information



Disease Group:	Endometrial	Supported By:	Gynecologic Oncology Group National Cancer Institute

Phase of Study:	Phase II	Return Visit:	Every 28 days (prior to each cycle) for assessment with post treatment follow-up every 3 months for the first 2 years and every 6 months for the next three years

Treatment Agents:	VEGF-Trap	Home Care:	none

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	n/a


Description/ Intervention:	Unavailable

Study Objectives / Outcomes

Primary Objectives

To assess the activity of VEGF-Trap for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response.
To determine the nature and degree of toxicity of VEGF-Trap as assessed by CTCAE v3.0 in this cohort of patients.

Secondary Objectives

To determine the duration of progression-free survival and overall survival.

Translational Research Objectives

To isolate, enumerate and phenotypically characterize circulating tumor cells (CTC) and circulating endothelial cells (CEC)/circulating endothelial precursors (CEP) recovered from blood drawn before and during treatment with VEGF-Trap.
To explore whether CTC and CEC/CEP counts or characteristics are associated with measures of clinical outcome and disease status.

Study Status Information



Study Activation / Registration Date:	06/02/2008

IRB Review and Approval Date:	04/15/2008

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	21-40

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments. Histologic confirmation of the original primary tumor is required.

2) All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be greater than or equal to 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or greater than or equal to 10 mm when measured by spiral CT.

3) Patients must have at least one "target lesion" to be used to assess response on this protocol 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 at least 90 days following completion of radiation therapy.

4) Patients must not be eligible for a higher priority GOG protocol, if one exists. In general, this would refer to any active GOG Phase III protocol for the same patient population.

5) Patients who have received one prior regimen must have a GOG Performance Status of 0, 1, or 2. Patients who have received two prior regimens must have a GOG Performance Status of 0 or 1.

6) Recovery from effects of recent surgery, radiotherapy, or chemotherapy. Patients should be free of active infection requiring antibiotics. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy is permitted. Any other prior therapy directed at the malignant tumor, including immunologic agents, must be discontinued at least three weeks prior to registration.

7) PRIOR THERAPY: Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma. Initial treatment may include high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment.

8) Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent endometrial disease according to the following definition: Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa.

9) (continued from no. 8) Note: Patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent endometrial disease, as defined above. However, due to the novel nature of biologic compounds, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy.

10) Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent endometrial disease.

11) Patients must have adequate: BONE MARROW FUNCTION: Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to Common Toxicity Criteria (CTCAE v3.0) grade 1. Platelets greater than or equal to100,000/mcl. HEPATIC FUNCTION: Bilirubin less than or equal to 1.5 x ULN (CTCAE v3.0 grade 1). SGOT and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE v3.0 grade 1). Neurologic function: Neuropathy (sensory & motor) less than or equal to CTCAE v3.0 grade 1. RENAL FUNCTION: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v3.0 grade 1.

12) Patients must have adequate: URINE PROTEIN CREATININE: (UPC) ratio must be less than 1.0 gm. If UPC ratio > or = 1 gm, collection of 24-hr urine measurement of urine protein is recommended. UPC ratio of spot urine is an estimation of the 24 urine protein excretion – a UPC ratio of 1 is roughly equivalent to a 24-hr urine protein of 1 gm. UPC ratio is calculated using one of the following formulas: (1) [urine protein]/[urine creatinine] – if both protein and creatinine are reported in mg/dL (2) [(urine protein) x 0.088]/[urine creatinine] – if urine creatinine is reported in mmol/L.

13) Patients must have adequate: BLOOD COAGULATION PARAMETERS: PT such that international normalized ratio (INR) is </= 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and a PTT </= 1.5 times the institutional upper limit of normal. Patients receiving low molecular weight heparin for the prevention or treatment of venous thromboembolic disease are eligible if considered clinically stable on their regimen.

14) Patients must have a baseline EKG performed prior to enrolling on study. The EKG must have QTc <500 msec and must not show evidence of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation must be less than 3 beats in a row).

15) Cardiac function: Cardiac ejection fraction must be within the institutional range of normal as measured by LVEF testing. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institution.

16) Patients must have signed an approved informed consent and authorization permitting release of personal health information.

17) Patients must meet pre-entry requirements as specified in the protocol.

18) Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception during the study and for at least 6 months after receiving the final treatment of VEGF-Trap.

Exclusion Criteria:

1) Patients who have had prior therapy with VEGF-Trap or other VEGF pathway targeted therapy.

2) With the exception of non-melanoma skin cancer and other specific malignancies as noted in numbers 10 and 11 below, patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last five years or whose previous cancer treatment contraindicates this protocol therapy are excluded.

3) Patients with serious, non-healing wound, ulcer, or bone fracture. This includes history of abdominal fistula or gastrointestinal perforation. Patients with an intra-abdominal abscess within 28 days prior to the first date of VEGF-Trap therapy are ineligible.

4) Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.

5) Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy or any brain metastases.

6) Patients with clinically significant cardiovascular disease including: 1. Uncontrolled hypertension, defined as systolic >140 mm Hg or diastolic >90 mm Hg. 2. Myocardial infarction or unstable angina within 6 months of the first date of VEGF-Trap therapy. 3. New York Heart Association (NYHA) Grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication. Women who have received prior treatment with an anthracycline (including doxorubicin and/or liposomal doxorubicin) and have an ejection fraction <50% will be excluded from the study.

7) Patients with clinically significant cardiovascular disease (continued) including: 4. CTCAE grade 2 or greater peripheral vascular disease. 5. History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of VEGF-Trap therapy.

8) Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

9) Patients undergoing invasive procedures as defined below: 1. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of VEGF-Trap therapy. 2. Major surgical procedure anticipated during the course of the study. 3. Minor surgical procedures, fine needle aspirates, or core biopsies within 7 days prior to the first date of VEGF-Trap therapy.

10) Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease.

11) Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of endometrial cancer within the last five years are excluded. Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease.

12) Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.

13) Patients may not be receiving any other investigational agents.

14) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with VEGF-Trap.

15) Patients under the age of 18.

16) Patients who are pregnant or nursing.

Links

Registration Number: NCT00462826
Study Information on Clinical Trials Registry (clinicaltrials.gov)