Pazopanib Hydrochloride, Paclitaxel, and Carboplatin in Treating Patients With Refractory or Resistant Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by European Organisation for Research and Treatment of Cancer - EORTC
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01402271
First received: July 23, 2011
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of pazopanib hydrochloride when given together with paclitaxel and carboplatin in treating patients with refractory or resistant ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer.


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Drug: carboplatin
Drug: paclitaxel
Drug: pazopanib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Maximum-tolerated dose of pazopanib hydrochloride, carboplatin, and paclitaxel (phase I) [ Designated as safety issue: Yes ]
  • Progression-free survival according to RECIST 1.1 at 1 year (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics of pazopanib, carboplatin, and paclitaxel (phase I) [ Designated as safety issue: No ]
  • Safety and tolerability according to CTCAE 4.0 (phase I and phase II) [ Designated as safety issue: Yes ]
  • Response rate (phase I and phase II) [ Designated as safety issue: No ]
  • Predictive biomarkers (phase I and phase II) [ Designated as safety issue: No ]
  • Overall survival (phase II) [ Designated as safety issue: No ]
  • Age-related subanalysis for toxicity and efficacy (cut-off 65 years old) (phase II) [ Designated as safety issue: Yes ]

Estimated Enrollment: 96
Study Start Date: July 2012
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pazopanib in combination with paclitaxel and carboplatin
Dose-escalation study of pazopanib in combination with paclitaxel and carboplatin given weekly in a group of patients with platinum-refractory or -resistant ovarian, fallopian tube or peritoneal carcinoma.
Drug: carboplatin Drug: paclitaxel Drug: pazopanib hydrochloride Other: laboratory biomarker analysis Other: pharmacological study

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01402271

Contacts
Contact: Ellen Peeters ellen.peeters@eortc.be

Locations
Belgium
U.Z. Gasthuisberg Recruiting
Leuven, Belgium
Principal Investigator: Ignace Vergote, MD, PhD         
Netherlands
Erasmus MC Recruiting
Rotterdam, Netherlands
Contact: Ingrid Boere, MD,PhD         
Principal Investigator: Ingrid Boere, MD, PhD         
Spain
Hospital Clínico Universitario San Carlos Recruiting
Madrid, Spain
Contact: Antonio Casado, MD, PhD         
Principal Investigator: Antonio Casado, MD, PhD         
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Ignace B. Vergote, MD, PhD U.Z. Gasthuisberg
Principal Investigator: Ingrid Boere, MD, PhD Erasmus MC
Principal Investigator: Antonio Casado, MD, PhD Hospital Clínico Universitario San Carlos
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01402271     History of Changes
Other Study ID Numbers: EORTC-55092, EU-21119, 2010-024077-39
Study First Received: July 23, 2011
Last Updated: July 3, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
recurrent ovarian epithelial cancer
recurrent fallopian tube cancer
recurrent primary peritoneal cavity cancer

Additional relevant MeSH terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Urogenital Neoplasms
Carboplatin
Paclitaxel
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014