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Phase IB-II, Open Label, Multicenter Feasibility Study of Pazopanib in Combination With Paclitaxel and Carboplatin in Patients With Platinum-Refractory/Resistant Ovarian, Fallopian Tube or Peritoneal Carcinoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Female
Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cavity Cancer

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Trial Information

Phase IB-II, Open Label, Multicenter Feasibility Study of Pazopanib in Combination With Paclitaxel and Carboplatin in Patients With Platinum-Refractory/Resistant Ovarian, Fallopian Tube or Peritoneal Carcinoma


OBJECTIVES:

Primary

- To determine the maximum-tolerated dose of pazopanib hydrochloride in combination with
paclitaxel and carboplatin in patients with platinum-refractory or -resistant ovarian
epithelial, fallopian tube, or peritoneal carcinoma. (Phase I)

- To determine the progression-free survival (PFS) at 1 year according to the RECIST 1.1
in these patients. (Phase II)

Secondary

- To determine the safety and adverse event profiles in these patients. (Phase I and
phase II)

- To determine the pharmacokinetics (PK) of this regimen using intensive sampling. (Phase
I)

- To determine if there is PK interaction (and if so, what kind of PK interaction)
between carboplatin and paclitaxel as well as pazopanib hydrochloride. (Phase I)

- To determine the response rate (RR) in these patients. (Phase I)

- To determine and evaluate predictive biomarkers. (Phase I and phase II)

- To determine the RR, overall survival (OS), and PFS of these patients. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of carboplatin, paclitaxel,
and pazopanib hydrochloride followed by a phase II randomized study.

- Phase I: Patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 30
minutes on day 1. Patients also receive oral pazopanib hydrochloride* once daily on
days 2-7. Treatment repeats every week for up to 18 courses**. Patients then continue
to receive oral pazopanib hydrochloride once daily in the absence of disease
progression or unacceptable toxicity.

NOTE: *Pazopanib hydrochloride is started in course 2 in order to evaluate the
pharmacokinetic of paclitaxel and carboplatin prior to pazopanib hydrochloride
administration.

- Phase II: Patients are stratified according to center, disease status
(platinum-refractory vs -resistant) and number of prior lines of treatment (1 vs more
than 1). Patients are randomized in a 2:1 ratio (arm II [experimental arm]: arm I
[standard arm]) to 1 of 2 treatment arms.

- Arm I (standard arm): Patients receive paclitaxel IV over 1 hour and carboplatin
IV over 30 minutes on day 1. Treatment repeats every week for up to 18 courses.

- Arm II (experimental arm): Patients receive paclitaxel IV over 1 hour and
carboplatin IV over 30 minutes on day 1. Patients also receive oral pazopanib
hydrochloride once daily on days 2-7. Treatment repeats every week for up to 18
courses**. Patients then continue to receive oral pazopanib hydrochloride once
daily in the absence of disease progression or unacceptable toxicity.

NOTE: **After course 9, chemotherapy will be interrupted for 1 week.

Blood samples are collected from some patients periodically for pharmacokinetic and
biomarker studies.

After completion of study treatment, patients are followed up at 3 weeks, every 3 months for
2 years, and then every 6 months for 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed ovarian epithelial, fallopian tube, or peritoneal carcinoma

- Recurrent disease

- Received at least 1 prior platinum treatment and developed platinum-refractory
disease (i.e., progression within 4 weeks of platinum administration) or
platinum-resistant disease (i.e., progression within 6 months after the last platinum
dose)

- There is no restriction on the number of prior lines of treatment

- Non-platinum treatment is allowed after proven platinum-resistance or
-refractory disease

- Evaluable (measurable or nonmeasurable) disease according to RECIST version 1.1
criteria

- Patients with refractory disease on weekly paclitaxel and carboplatin regimen are
excluded (phase II only)

- No known gastrointestinal intraluminal metastatic lesions with risk of bleeding

- No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

- No known brain metastases or leptomeningeal disease

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- Absolute neutrophil count ≥ 1.5 x 10^9/L

- Hemoglobin ≥ 9 g/dL

- Platelet count ≥ 100 x 10^9/L

- PT, aPTT, or INR ≤ 1.2 times upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 times ULN*

- ALT and AST ≤ 2.5 times ULN*

- Serum creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 50 mL/min

- Urine protein creatinine ratio < 1 OR 24-hour urine protein < 1 g

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during study therapy

- No other prior primary or recurrent malignancies treated within the past 2 years
except for completely resected non-melanomatous skin carcinoma or successfully
treated carcinoma in situ of the skin or uterine cervix

- No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
similar or related to paclitaxel, carboplatin, and pazopanib hydrochloride

- Able to receive infusions of paclitaxel and carboplatin

- Able to swallow pazopanib hydrochloride tablets

- No unstable or serious condition (e.g., uncontrolled infection requiring systemic
therapy)

- No history of any of the following cardiovascular conditions within the past 6
months:

- Myocardial infarction

- Unstable angina

- Symptomatic peripheral vascular disease

- NYHA class III-IV congestive heart failure

- LVEF > 50% as assessed by ultrasound or MUGA scan, if clinically indicated

- No inadequately controlled hypertension (SBP ≥ 140 mm Hg or DBP ≥ 90 mm Hg)

- Initiation or adjustment of blood pressure medication is permitted prior to the
study entry

- No prolonged corrected QT interval (QTc) defined as > 480 msecs using Bazett formula

- No history of cerebrovascular accident within the past 6 months, including any of the
following:

- Transient ischemic attack

- Pulmonary embolism

- Untreated deep venous thrombosis (DVT)

- Patients with recent DVT who have been treated with therapeutic
anti-coagulating agents for at least 6 weeks are eligible

- No evidence of active bleeding or bleeding diathesis

- No clinically significant gastrointestinal (GI) tract abnormalities that may increase
the risk for GI bleeding including, but not limited to, any of the following:

- Active peptic ulcer disease

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

- History of bowel obstruction (excluding postoperatively [i.e., within 4 weeks
post surgery])

- Other GI conditions with increased risk of perforation

- No clinically significant GI abnormalities that may affect absorption of
investigational product including, but not limited to, any of the following:

- Malabsorption syndrome

- Major resection of stomach or small bowel

- No hemoptysis in excess of 2.5 mL (one-half teaspoon) within 8 weeks prior to first
dose of study drug

- No psychological, familial, sociological, or geographical condition potentially
hampering compliance with the study protocol and follow-up schedule

- No trauma within the past 28 days

- No prior non-healing wounds, fracture, or ulcer

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No ongoing toxicity from prior anticancer therapy > grade 1 and/or that is
progressing in severity, except for alopecia and ≤ grade 2 peripheral neuropathy

- No cardiac angioplasty or stenting within the past 6 months

- No coronary artery bypass graft surgery within the past 6 months

- At least 14 days since prior radiotherapy, surgery, or tumor embolization ,
chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal
therapy (28 days for drugs with a longer half-life)

- At least 14 days since prior (28 days for drugs with a longer half-life) and no
concurrent prohibited medications

- At least 28 days since prior major surgery (procedures such as catheter placement and
diagnostic endoscopic procedures are not considered to be major)

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose of pazopanib hydrochloride, carboplatin, and paclitaxel (phase I)

Safety Issue:

Yes

Principal Investigator

Ignace B. Vergote, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

U.Z. Gasthuisberg

Authority:

Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:

EORTC-55092

NCT ID:

NCT01402271

Start Date:

July 2012

Completion Date:

Related Keywords:

  • Fallopian Tube Cancer
  • Ovarian Cancer
  • Primary Peritoneal Cavity Cancer
  • recurrent ovarian epithelial cancer
  • recurrent fallopian tube cancer
  • recurrent primary peritoneal cavity cancer
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial

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