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A Randomized Phase IIB Evaluation of Weekly Paclitaxel (NSC #673089) Plus Pazopanib (NSC #737754) (IND #75648) Versus Weekly Paclitaxel Plus Placebo in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma

Phase 2
18 Years
Open (Enrolling)
Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer

Thank you

Trial Information

A Randomized Phase IIB Evaluation of Weekly Paclitaxel (NSC #673089) Plus Pazopanib (NSC #737754) (IND #75648) Versus Weekly Paclitaxel Plus Placebo in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma


I. To estimate the progression-free survival hazard ratio of the combination of weekly
paclitaxel and pazopanib (pazopanib hydrochloride) compared to weekly paclitaxel and placebo
in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal


I. To determine the frequency and severity of adverse events as assessed by CTCAE.

II. To estimate and compare the proportion of patients responding to therapy by RECIST,
CA125 response, the overall survival (OS), and the duration of response in each arm.


I. To explore the association between plasma cytokines and angiogenic markers and
progression-free and overall survival.

II. To explore the association between single-nucleotide polymorphisms (SNPs) and
progression-free and overall survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo orally
(PO) daily on days 1-28.

ARM II: Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days

In both arms, treatment repeats 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.

Inclusion Criteria:

- Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma

- Histologic documentation of the original primary tumor is required via the
pathology report

- Patients must have measurable disease or non-measurable (detectable) disease

- Measurable disease is defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded)

- Each lesion must be greater than or equal to 10 mm when measured by CT,
MRI, or caliper measurement by clinical exam; or greater than or equal to
20 mm when measured by chest x-ray

- Lymph nodes must be greater than or equal to 15 mm in short axis when
measured by CT or MRI

- Patients with measurable disease must have at least one "target lesion" to
be used to assess response on this protocol as defined by RECIST 1.1

- 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

- Non-measurable (detectable) disease in a patient is defined in this protocol as
one who does not have measurable disease but has at least one of the following

- Ascites and/or pleural effusion attributed to tumor

- Solid and/or cystic abnormalities on radiographic imaging that do not meet

- Patients must not be eligible for a higher priority GOG protocol, if one exists

- Patients must not be eligible for a currently active, phase II cytotoxic
protocol in platinum-resistant disease

- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound

- This initial treatment may have included intraperitoneal therapy, consolidation,
biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab), or extended
therapy administered after surgical or non-surgical assessment

- If patients were treated with paclitaxel for their primary disease, this can
have been given weekly or every 3 weeks

- Treatment with weekly paclitaxel for recurrent or persistent disease is NOT

- No history or evidence upon physical examination of CNS disease, including primary
brain tumor or any brain metastases

- Patients who have received one prior regimen must have a GOG performance status of 0,
1, or 2

- Patients who have received two or three prior regimens must have a GOG performance
status of 0 or 1

- Absolute neutrophil count (ANC) greater than or equal to 1,500/µL

- Platelets greater than or equal to 100,000/µL

- Hemoglobin greater than or equal to 9 g/dL

- Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)

- PT such that international normalized ratio (INR) is less than or equal to 1.5 x ULN
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin)

- PTT less than or equal to 1.5 x ULN

- If urine protein is 2+ or higher, 24-hour urine protein should be obtained and the
level must be < 1000 mg (<1.0 g/24hrs) for patient enrollment

- Bilirubin less than or equal to 1.5 x ULN

- AST and ALT less than or equal to 2.5 x ULN

- Subjects who have BOTH bilirubin greater than ULN and AST/ALT greater than ULN are
not eligible

- Alkaline phosphatase less than or equal to 2.5 x ULN

- Patients must have normal baseline thyroid function tests (TSH, T3, T4)

- A history of hypothyroidism and/or hyperthyroidism is allowed, as long as the
patient has stable well-controlled thyroid function for a minimum of 2 months

- Neuropathy (sensory and motor) less than or equal to grade 1

- Patients should be free of active infection requiring antibiotics (with the exception
of uncomplicated UTI)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use an effective form of contraception

- Patients must be capable of taking and absorbing oral medications and be clear of the

- Any lesion, whether induced by tumor, radiation, or other conditions, that makes
it difficult to swallow tablets

- Active peptic ulcer disease

- Malabsorption syndrome

- Patients with personal or family history of congenital long QTc syndrome are NOT

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer and other specific malignancies, are excluded if there is
any evidence of other malignancy being present within the last three years

- No clinically significant cardiovascular disease including any of the following:

- Uncontrolled hypertension, defined as systolic greater than 140 mm Hg or
diastolic greater than 90 mm Hg despite antihypertensive medications

- Congenital long QT syndrome or baseline QTc greater than 480 milliseconds

- Myocardial infarction or unstable angina within 6 months prior to registration

- New York Heart Association (NYHA) class II or greater congestive heart failure

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation) or serious cardiac arrhythmia requiring medication

- This does not include asymptomatic atrial fibrillation with controlled
ventricular rate

- Patients who have received prior treatment with an anthracycline (including
doxorubicin and/or liposomal doxorubicin) must have an echocardiogram assessment
and are excluded if they have an ejection fraction less than 50%

- CTCAE Grade 2 or greater peripheral vascular disease (at least brief less than
24 hrs) episodes of ischemia managed non-surgically and without permanent

- History of cardiac angioplasty or stenting within 6 months prior to registration

- History of coronary artery bypass graft surgery within 6 months prior to

- Arterial thrombosis within 6 months prior to registration

- No serious non-healing wound, ulcer, or bone fracture

- Includes history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess within 28 days prior to the first date of study

- No patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major

- No seizures that are not controlled with non-enzyme-inducing anticonvulsants

- No transient ischemic attack (TIA) or subarachnoid hemorrhage within six months prior
to the first date of study treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to pazopanib

- No known HIV-positive subjects on combination antiretroviral therapy

- No condition that may increase the risk of gastrointestinal bleeding or
gastrointestinal perforation, including:

- Active peptic ulcer disease

- Known gastrointestinal intraluminal metastatic lesions (gastrointestinal serosa
metastatic lesions are permitted)

- Inflammatory bowel disease (e.g., ulcerative colitis, Crohn disease)

- Patients with clinical symptoms or signs of gastrointestinal obstruction

- Patients who require parenteral hydration and/or nutrition

- No history of hemoptysis in excess of 2.5 mL (½ teaspoon) within 8 weeks prior to
first dose of pazopanib

- No uncontrolled intercurrent illness including, but not limited to, psychiatric
illness/social situations that would limit compliance with study requirements

- Grapefruit juice and St. John wort are not allowed on this study

- Recovered from effects of recent surgery, radiotherapy, or chemotherapy

- Patients are allowed to receive, but are not required to receive, two additional
cytotoxic regimens for management of recurrent or persistent disease, with no more
than 1 non-platinum, non-taxane regimen

- No previous treatment with weekly paclitaxel for recurrent or persistent disease

- No previous cancer treatment that contraindicates this protocol therapy

- Patients are allowed to receive, but are not required to receive, biologic/targeted
(non-cytotoxic) therapy as part of their primary treatment regimen

- Patients are allowed to receive, but are not required to receive, poly (ADP-ribose)
polymerase (PARP) inhibitors for management of primary or recurrent/persistent
disease (either alone or in combination with cytotoxic chemotherapy)

- For the purposes of this study, PARP inhibitors will be considered "cytotoxic"

- PARP inhibitors will NOT count as a prior regimen when given alone

- Any hormonal therapy directed at the malignant tumor must be discontinued at least
one week prior to registration

- Any other prior therapy directed at the malignant tumor, including chemotherapy,
biological/targeted (non-cytotoxic) agents, and immunologic agents, must be
discontinued at least three weeks prior to registration

- Chimeric or human or humanized monoclonal antibodies (including bevacizumab) or
VEGF-receptor fusion proteins (including VEGF TRAP/aflibercept) must be discontinued
for at least 12 weeks prior to registration

- At least 4 weeks must have elapsed since the patient underwent any major surgery
(e.g., major: laparotomy, laparoscopy, thoracotomy, video-assisted thorascopic
surgery [VATS]); there is no restriction on minor procedures (e.g., minor: central
venous access catheter placement, ureteral stent placement or exchange, paracentesis,

- No prior surgical procedures affecting absorption including, but not limited to,
major resection of stomach or small bowel

- Patients must have NOT received any biologic/targeted (non-cytotoxic) therapy
targeting the VEGF and/or PDGF pathways for management of recurrent or persistent

- Any concomitant medications that are associated with a risk of QTc prolongation
and/or Torsades de Pointes should be discontinued or replaced with drugs that do not
carry these risks, if possible

- Strong inhibitors of CYP3A4 are prohibited

- Strong inducers of CYP3A4 are prohibited

- No previous treatment with pazopanib

- No prior radiotherapy to any portion of the abdominal cavity or pelvis within the
last three years

- 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

- No prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment
of ovarian, fallopian tube, or primary peritoneal cancer within the last three years

- Patients may have received prior adjuvant chemotherapy for localized breast
cancer, provided that it was completed more than three years prior to
registration and the patient remains free of recurrent or metastatic disease

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Efficacy of each treatment regimen

Outcome Description:

Evaluated using the Cox proportional hazards and stratified by platinum-free interval, measurable disease status, and prior use of bevacizumab. Maximum likelihood estimate of the logarithm of the hazard ratio of Arm 2 to Arm 1 for disease progression or death (PFS endpoint) will be calculated.

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Debra Richardson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

December 2011

Completion Date:

Related Keywords:

  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms



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