MDACC Study Summary GOG 0213

Study Summary
No. GOG 0213:.......Fallopian Tube; Ovary; Peritoneum......Robert Coleman......Gynecologic Oncology

Study Summary Title



Study Summary Number:	GOG 0213

Study Title:	A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel Alone or in Combination with Bevacizumab (NSC #704865, IND #7921) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Peritoneal Primary, and Fallopian Tube Cancer. NCI-Supplied Agent: Bevacizumb (NSC #704865, IND #7921)

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:	Fallopian Tube Ovary Peritoneum	Supported By:	Genentech provides agent which is distributed via the National Cancer Institute Gynecologic Oncology Group

Phase of Study:	Phase III	Return Visit:	1 pre-surgery visit (eligible pts only) 1 pre-chemotx visit treatment: every 21 days until disease progression, toxicity precludes further treatment or pt refuses treatment post treatment: every 3 months for 2 years, then every 6 months for 10 years

Treatment Agents:	Bevacizumab Carboplatin Paclitaxel Surgical Procedure	Home Care:	none

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

Estimated Length of Stay in Houston:	One 3-5 day hospital stay for surgery.

Description/
Intervention:

The goal of this clinical research study is to compare the combination of
carboplatin, paclitaxel, and bevacizumab to the standard combination of
carboplatin and paclitaxel alone, in treating ovarian, primary peritoneal, or
Fallopian tube cancer. Researchers will compare how effective the treatments
are, how long the participants go without evidence of cancer growth, and how
the treatments affect their quality of life.

Researchers will also study if a second surgery to remove tumor tissue,
followed by chemotherapy, can help you stay disease-free longer.

Another purpose of this study is to test samples of your blood, some of your
tumor if left over from an earlier surgery and some of your tumor and normal
tissue if left over from surgery performed as part of this study. The purpose
of this research is to learn if this testing can be used in the future to
decide which patients may respond to treatment, have side effects, or have a
good outcome.

Study Objectives / Outcomes

Primary Objectives
To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases the duration of overall survival in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary, or Fallopian tube cancer.

To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases the duration of overall survival relative to secondline paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary, or Fallopian tube cancer.

Secondary objectives
To determine if the addition of bevacizumab to the second-line and maintenance phase of treatment increases the duration of progression-free survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary, or Fallopian tube cancer.

To prospectively determine the incidence of carboplatin and paclitaxel hypersensitivity in these patients undergoing retreatment with both agents as first recurrence therapy.

To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases quality of life (QOL) in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary, or Fallopian tube cancer, as measured by the FACT-O trial outcome index and Rand SF-36 physical functioning scale.

To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases QOL relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary, or Fallopian tube cancer.

Translational Research Objectives
The following translational research objectives will be evaluated in the tissue and serum specimens submitted from GOG-0213 patients undergoing secondary surgical cytoreduction.

To define molecular and biochemical profiles associated with the duration of progression-free survival in platinum-sensitive recurrent ovarian, peritoneal primary, or Fallopian tube carcinoma treated with combination chemotherapy with or without bevacizumab followed with or without maintenance bevacizumab therapy in the presence or absence of secondary surgical cytoreduction.

To identify molecular determinants that predict sensitivity or resistance to carboplatin and paclitaxel with or without bevacizumab followed with or without maintenance bevacizumab therapy.

Study Status Information



Study Activation / Registration Date:	03/25/2008

IRB Review and Approval Date:	03/25/2008

Study Type:	Phase Iii

Recruitment Status:	Open

Projected Accrual:	660

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 histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or Fallopian tube carcinoma, which is now recurrent.

2) Patients with the following histologic epithelial cell types are eligible: Serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.).

3) Patients must have had a complete response to front-line platinum-taxane therapy (at least three cycles).

4) (continued from #3) A complete response to front-line chemotherapy must include: negative physical exam, negative pelvic exam, normalization of CA125, if elevated at baseline. Although not required, any radiographic assessment of disease status (CT, MRI, PET/CT, etc) obtained following the completion of primary therapy should be considered negative for disease.

5) (continued from #4) All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane). Front-line therapy may have included a biologic agent (i.e. bevacizumab).

6) (continued from #5) Front-line treatment may include maintenance therapy following complete clinical or pathological response. However, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease. Patients receiving maintenance biological therapy are ELIGIBLE provided their recurrence is documented more that 6 months from primary cytotoxic chemotherapy AND a minimum 4 weeks has elapsed since their last infusion of biologic therapy.

7) (continued from # 6) Patients who have undergone reassessment laparotomy or laparoscopy following primary therapy are eligible for this study as long as they demonstrated a pathologic complete response based on the surgical assessment (i.e. all obtained specimens were histologically negative for disease).

8) Patients just have recurrence documented by elevated CA-125 (biochemical recurrence) or clinically evident measurable or non-measurable recurrent disease as defined below. For the purpose of this study:

9) (continued from #8) Biochemical recurrence is defined as a CA-125 greater than or equal to two times the upper normal limit. Patients whose CA-125 is less than 100 U/mL must undergo a second confirmatory value with a period of not more than 4 weeks. Patients with a level greater than or equal to 100 U/mL may be entered without confirmatory measurement. The CA-125 assessment for eligibility must be done at least 4 weeks after paracentesis or other surgical procedures.

10) (continued from #9) Measurable disease (RECIST) 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 more than or equal to 20 mm when measured by conventional techniques, MRI or CT, or more than or equal to 10 mm when measured by spiral CT. Non-measurable disease is either symptomatic ascites or pleural effusion.

11) (continued from no. 10) Non-measurable disease includes patients with symptomatic ascites or pleural effusions, lesions that do not meet RECIST criteria (as defined in # 10), or biopsy proven recurrence. Patients with clinically evident non-measurable disease must have either an elevated CA-125 (as defined in # 9) or histologic confirmation of recurrence.

12) Patients must have adequate: Bone marrow function: Absolute neutrophil count (ANC) >/= to 1,500/mm3, equivalent to Common Toxicity Criteria for Adverse Events v3.0 (CTCAE) Grade1. Platelets >/= to 100,000/mm3. (CTCAE Grade 0-1). Renal function: Creatinine (non-IDMS) </= 1.5 x institutional upper limit normal (ULN), CTCAE Grade 1. Hepatic function: Total bilirubin </= 1.5 ULN (CTCAE Grade 1). SGOT/AST and Alkaline Phosphatase </= 2.5 times the upper limit of normal in the absence of liver metastasis. SGOT/AST and Alkaline Phosphatase < 5.0 times ULN in the presence of liver metastasis.

13) Patients must have a urine protein-to-creatinine ratio (UPCR) < 1.0 mg/dL. A UPCR of 1.0 is equivalent to 1.0 gram of protein in a 24-hour urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send the sample to the lab with a request for urine protein and creatinine levels [separate requests]. The lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL). The UPCR is derived as: protein concentration (mg/dL) / creatinine concentration (mg/dL).

14) Patients who are not candidates for surgical cytoreduction are eligible for the chemotherapy randomization. Patients are not considered candidates for surgical cytoreduction if complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking.

15) Patients must have met the pre-entry requirements.

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

17) Patients must have a GOG Performance Status of 0, 1, or 2.

18) Patients must be at least 18 years old.

Exclusion Criteria:

1) Patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen).

2) Patients receiving concurrent immunotherapy, or radiotherapy.

3) Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded.

4) Patients with a prior histologic diagnosis of borderline, low malignant potential (grade 0) epithelial carcinoma that was surgically resected and who subsequently developed an unrelated, new invasive epithelial ovarian or peritoneal primary cancer are eligible provided that they meet the criteria listed in Inclusion Criteria #2 above.

5) Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation.

6) Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other than ovarian, fallopian tube, and primary peritoneal) are excluded.

7) Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: Stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions.

8) Patients with uncontrolled infection.

9) Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy.

10) Patients with >/= grade 2 peripheral neuropathy.

11) Patients with a history of allergic reactions to carboplatin and/or paclitaxel or chemically similar compounds. Patients with allergic (hypersensitivity) reactions to these chemotherapeutic agents are NOT excluded IF they were successfully retreated following a desensitization program or protocol

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

13) Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are nursing are not eligible for this trial.

14) Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy.

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

16) Patients with a history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases or a history of stroke within 5 years of the first date of treatment on this study.

17) Patients with significant cardiac conduction abnormalities, i.e. PR interval > 0.24 sec or 2nd or 3rd degree AV block; uncontrolled hypertension, defined as systolic > 140 mm Hg or diastolic > 90 mm Hg; myocardial infarction, cardiac arrhythmia or unstable angina < 6 months prior to registration.

18) Patients with New York Heart Association (NYHA) Grade II or greater congestive heart failure; serious cardiac arrhythmia requiring medication; grade II or greater peripheral vascular disease (exception: episodes of ischemia < 24 hrs in duration, that are managed non-surgically and without permanent deficit).

19) Patients who have had a major surgical procedure, open biopsy, dental extractions or other dental surgery/procedure that results in an open wound, or significant traumatic injury within 28 days prior to the first date of treatment on this study, or anticipation of need for major surgical procedure during the course of the study; patients with placement of vascular access device or core biopsy within 7 days prior to the first date of treatment on this study.

20) Patients undergoing pre-treatment secondary cytoreduction will undergo therapy with bevacizumab on cycle #2.

21) Patients undergoing pre-treatment surgery for purposes other than cytoreduction may also participate provided they meet eligibility. Patients randomized to arms containing bevacizumab must wait a minimum of 28 days since that procedure to begin protocol treatment. Patients who undergo an uncomplicated port placement must wait a minimum of 7 days to begin protocol treatment.

Links

Registration Number: NCT00565851
Study Information on Clinical Trials Registry (clinicaltrials.gov)