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A Phase II Trial of Bevacizumab With Carboplatin and Weekly Paclitaxel as First-Line Treatment in Epithelial Ovarian, Primary Peritoneal, and Fallopian Tube Carcinoma


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Epithelial Ovarian Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer

Thank you

Trial Information

A Phase II Trial of Bevacizumab With Carboplatin and Weekly Paclitaxel as First-Line Treatment in Epithelial Ovarian, Primary Peritoneal, and Fallopian Tube Carcinoma


Standard chemotherapy for newly diagnosed epithelial ovarian, primary peritoneal, or
fallopian tube cancer is usually a combination of 2 chemotherapy drugs called carboplatin
and paclitaxel. This treatment has been found to be effective, but the cancer often comes
back, requiring additional treatment. For this study, researchers will give carboplatin,
bevacizumab, and weekly paclitaxel to see if the treatment is effective and safe in treating
the disease.

The Study Drugs:

Bevacizumab is designed to block the growth of blood vessels that supply nutrients necessary
for tumor growth. This may prevent or slow down the growth of cancer cells.

Carboplatin is designed to interfere with the growth of cancer cells by stopping cell
division.

Paclitaxel is designed to block the mechanisms of cell division in cancer cells, causing
them to die.

Study Drug Administration:

If you choose to take part in this study, you will receive up to 6 "cycles" of treatment
with the study drugs. Each cycle is 21 days (3 weeks) long.

On Day 1 of Cycle 1, you will receive paclitaxel and carboplatin by vein. Paclitaxel is
given first over about 3 hours, followed by carboplatin over about 1 hour.

On Days 8 and 15 of Cycle 1, you will only receive paclitaxel by vein over about 3 hours.

On Day 1 of Cycles 2-6, you will receive paclitaxel, carboplatin, and bevacizumab by vein.
Paclitaxel is given first over about 3 hours, followed by carboplatin over about 1 hour, and
then bevacizumab over about 1 ½ hours.

If you tolerate your first dose of bevacizumab well, the dose of bevacizumab during Cycle 3
may be given over 60 minutes. If you tolerate the 60 minute dose well, the bevacizumab
doses during Cycles 4, 5, and 6 may be given over 30 minutes.

On Days 8 and 15 of Cycles 2-6, you will only receive paclitaxel by vein over about 3 hours.

Before you begin each treatment, you will receive the drug dexamethasone by vein to help
decrease the risk of study drug side effects. If the study doctor thinks it is needed, you
may also receive other drugs (such as cimetidine and diphenhydramine) by vein to help
prevent side effects such as nausea and allergic reaction.

Study Visits:

Before starting each cycle:

- Your medical history will be recorded, including a list of any drugs you may be taking.

- Your performance status will be recorded.

- You will have a physical exam, including measurement of weight and vital signs.

- A pelvic exam will be performed if the study doctor thinks it is necessary.

- You will be asked about any side effects you may be experiencing.

- Blood (about 3 teaspoons) will be drawn for routine tests.

- Blood (about 1 teaspoon) will be drawn to measure levels of CA125.

- If the study doctor thinks it is necessary, you will have a CT or MRI scan of the
abdomen and pelvis.

Before Cycles 2, 4, and 6 only, urine will be collected for routine tests.

Length of Study:

You may remain on study for up to 6 cycles. You will be taken off study early if the
disease gets worse or you experience any intolerable side effects.

End-of-Study Visit:

Within 4 weeks after your last dose of study drugs, you will have an end-of-study visit, at
which the following tests and procedures will be performed:

- Your medical history will be recorded, including a list of any drugs you may be taking.

- You will have a physical exam, including measurement of weight, vital signs, and a
pelvic exam.

- Your performance status will be recorded.

- Blood (about 4 teaspoons) will be drawn for routine tests and to measure levels of
CA125.

- Urine will be collected for routine tests.

- You will have a CT scan or MRI scan of the abdomen and pelvis.

- If the study doctor thinks it is necessary, you will have a chest x-ray and/or an ECG.

Long-Term Follow-Up:

After your end-of-study visit, you will have long-term follow-up visits every 3 months for 2
years, at which the following tests and procedures will be performed:

- Your medical history will be recorded, including a list of any drugs you may be taking.

- You will have a physical exam, including measurement of weight, vital signs, and a
pelvic exam.

- Your performance status will be recorded.

- Blood (about 4 teaspoons) will be drawn for routine tests and to measure levels of
CA125.

- Urine will be collected for routine tests.

- You will have a CT scan or MRI scan of the abdomen and pelvis.

- If the study doctor thinks it is necessary, you will have a chest x-ray and/or an ECG.

If you are unable to come to M. D. Anderson for your long-term follow-up visits, researchers
will call you on the phone every 3 months for 2 years to ask you questions about how you are
doing. Your doctor will tell you if any standard tests and procedures need to be performed.
The phone calls should last about 10 minutes each time.

This is an investigational study. Bevacizumab, carboplatin, and paclitaxel are each FDA
approved and commercially available for the treatment of many types of cancer. The
combination of carboplatin and paclitaxel is FDA approved and commercially available for the
treatment of epithelial ovarian, primary peritoneal, or fallopian tube cancer. At this
time, the addition of bevacizumab to the combination of carboplatin and paclitaxel is not
FDA approved and is being used in research only.

Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients with a histologic diagnosis of epithelial ovarian cancer, peritoneal primary
carcinoma or fallopian tube cancer; FIGO stage III and IV defined surgically at the
completion of initial abdominal surgery and with appropriate tissue available for
histologic evaluation. The minimum surgery required is an abdominal surgery providing
tissue for histologic evaluation and establishing and documenting the primary site
and stage, as well as a maximal effort at tumor debulking.

2. (continued from no. 1) Those patients with stage III cancer in which the largest
maximal diameter of any residual tumor implant at the completion of this initial
surgery is no greater than 1 cm will be defined as optimal; all others will be
defined as suboptimal.

3. The histologic features of the tumor must be compatible with a primary Müllerian
epithelial adenocarcinoma. 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, Malignant Brenner's Tumor, Adenocarcinoma
N.O.S. Patients may have co-existing fallopian tube carcinoma in-situ so long as the
primary origin of invasive tumor is ovarian, peritoneal or fallopian tube.

4. Patients must be entered no later than 12 weeks after initial surgery performed for
the combined purpose of diagnosis, staging and cytoreduction.

5. Patients with measurable and non-measurable disease are eligible. Patients may or may
not have cancer-related symptoms.

6. Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy
as indicated at the lowest effective dose(s) for control of menopausal symptoms at
any time, but not progestins for management of anorexia while on protocol directed
therapy.

7. Patients with an ECOG Performance Status of 0, 1, or 2.

8. Patients must have normal organ and marrow function as defined below: leukocytes
>3,000/mcL; absolute neutrophil count >1,500/mcL; platelets >100,000/mcL; total
bilirubin <1.5 X institutional upper limits of normal; AST(SGOT)/ALT(SGPT) <2.5 X
institutional upper limit of normal; Alkaline phosphatase (AP) <2.5 X institutional
upper limit of normal; creatinine <1.5X institutional upper limit of normal OR
creatinine clearance >50 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal

9. Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

1. Patients with borderline epithelial ovarian tumor (formerly "tumors of low malignant
potential") or recurrent invasive epithelial ovarian, primary peritoneal or fallopian
tube cancer treated with surgery only are not eligible. Patients with a prior
diagnosis of a borderline tumor that was surgically resected and who subsequently
develop an unrelated, new invasive epithelial ovarian, peritoneal primary or
fallopian tube cancer are eligible, provided that they have not received prior
chemotherapy for any ovarian tumor.

2. Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis 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.

3. Patients who have received prior chemotherapy for any abdominal or pelvic tumor
including neo-adjuvant chemotherapy for their ovarian, primary peritoneal or
fallopian tube cancer 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.

4. Patients who have received any targeted therapy (including but not limited to
vaccines, antibodies, tyrosine kinase inhibitors) or hormonal therapy for management
of their epithelial ovarian or peritoneal primary cancer.

5. Patients who are currently participating or planning to participate in an
experimental drug study other than a Genentech-sponsored bevacizumab cancer study or
who are receiving other investigational agents.

6. 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 IB; 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.

7. With the exception of superficial basal cell and superficial squamous (skin) cell,
carcinoma in situ of the cervix and other specific malignancies as noted above,
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.

8. Patients with acute hepatitis or active infection that requires parenteral
antibiotics.

9. Patients with serious non-healing wound, ulcer, or untreated bone fracture. This
includes a history of abdominal fistula or gastrointestinal perforation within 6
months prior to Day 1. Patients with granulating incisions healing by secondary
intention with no evidence of fascial dehiscence or infection are eligible but
require weekly wound examinations until closure.

10. Patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy (in the absence of
therapeutic anticoagulation), or tumor involving major vessels.

11. History of hemoptysis (>/=1/2 teaspoon of bright red blood per episode) within 1
month prior to Day 1.

12. Patients with history or evidence upon physical examination of CNS disease, including
primary brain tumor, seizures not controlled with standard medical therapy, any brain
metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic
attack (TIA) or subarachnoid hemorrhage within six months of the first date of
treatment on this study.

13. Patients with clinically significant cardiovascular disease. This includes: 1)
Uncontrolled hypertension, defined as systolic > 140 mm Hg or diastolic > 90 mm Hg;
2) Myocardial infarction or unstable angina < 6 months prior to registration; 3) New
York Heart Association (NYHA) Grade II or greater congestive heart failure; 4)
Serious cardiac arrhythmia requiring medication. This does not include asymptomatic,
atrial fibrillation with controlled ventricular rate

14. (continued from no. 13) CTCAE Grade 2 or greater peripheral vascular disease (at
least brief (<24 hrs) episodes of ischemia managed non-surgically and without
permanent deficit); Prior history of hypertensive crisis or hypertensive
encephalopathy; Significant vascular disease (e.g., aortic aneurysm, requiring
surgical repair or recent peripheral arterial thrombosis) within 6 months prior to
Day 1

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

16. Patients with known hypersensitivity to any component of bevacizumab

17. Patients with clinically significant proteinuria at screening as demonstrated by
urine protein:creatinine (UPCR) ratio >/= 1.0 at screening. The UPCR has been found
to correlate directly with the amount of protein excreted in a 24 hour urine
collection. Specifically, 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 sample to lab with request for
urine protein and creatinine levels [separate requests].

18. (continued from no. 17) The lab will measure protein concentration (mg/dL) and
creatinine concentration (mg/dL). The UPCR is derived as follows: protein
concentration (mg/dL)/creatinine (mg/dL).

19. Patients with or with anticipation of invasive procedures as defined below: Major
surgical procedure within 28 days of initiating bevacizumab or major procedures
anticipated during the course of the study. This includes, but is not limited to
abdominal surgery (laparotomy or laparoscopy) prior to disease progression, such as
colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or
second look surgery.

20. (continued from no. 19) Core biopsy or other minor surgical procedure, excluding
placement of a vascular access device, within 7 days prior to the first date of
bevacizumab therapy

21. Patients with ECOG Performance Grade of 3 or 4

22. Patients who are pregnant (positive pregnancy test) or nursing. Use of effective
means of contraception (men and women) in subjects of child-bearing potential. To
date, no fetal studies in animals or humans have been performed. The possibility of
harm to a fetus is likely. Bevacizumab specifically inhibits VEGF, which is
responsible for formation of new blood vessels during development, and antibodies can
cross the placenta. Therefore, bevacizumab should not be administered to pregnant
women.

23. (continued from no. 22) Subjects will be apprised of the large potential risk to a
developing fetus. It is not known whether bevacizumab is excreted in human milk.
Because many drugs are excreted in human milk, bevacizumab should not be administered
to nursing women. Patients of childbearing potential must agree to use contraceptive
measures during study therapy and for at least six months after completion of
bevacizumab therapy.

24. Patients under the age of 18.

25. Patients who have received prior therapy with any anti-VEGF drug, including
bevacizumab.

26. Patients with clinical symptoms or signs of gastrointestinal obstruction and who
require parenteral hydration and/or nutrition.

27. Patients with medical history or conditions not otherwise previously specified which
in the opinion of the investigator should exclude participation in this study.

28. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

29. Known HIV-positive patients on combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with bevacizumab. In
addition, these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.

30. Inability to comply with study and/or follow-up procedures.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients with Treatment Success

Outcome Description:

Treatment Success is defined as a patient completing at least 4 cycles of combination therapy (Bevacizumab with Carboplatin and weekly Paclitaxel) regardless of delay or dose modification.

Outcome Time Frame:

4 cycles of 21 days

Safety Issue:

Yes

Principal Investigator

Anil Sood, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2009-0186

NCT ID:

NCT01097746

Start Date:

April 2010

Completion Date:

Related Keywords:

  • Epithelial Ovarian Cancer
  • Primary Peritoneal Cancer
  • Fallopian Tube Cancer
  • Cancer
  • Fallopian Tube
  • Ovary
  • Peritoneum
  • Epithelial ovarian
  • Paclitaxel
  • Carboplatin
  • Bevacizumab
  • Taxol
  • Avastin
  • Paraplatin
  • Carcinoma
  • Surgery
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

UT MD Anderson Cancer Center Houston, Texas  77030