Clinical Trial Investigating Pazopanib in Patients With Platinum-resistant Advanced Ovarian Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Grupo Español de Investigación en Cáncer de Ovario
ClinicalTrials.gov Identifier:
NCT01262014
First received: December 15, 2010
Last updated: March 19, 2012
Last verified: March 2012
  Purpose

Given the low Responses Rates and short survival times achieved with conventional cytotoxic agents in resistant ovarian cancer patients, new treatment options are needed in this patient population.Antiangiogenic therapy has an important role in this group of patients and Pazopanib in particular. We are going to study if Pazopanib is able to control disease-related symptoms minimizing the side effects of treatment. This aspect is very important in the treatment of resistant ovarian cancer patient since our treatment is palliative without any impact in overall survival. So our goal is to study the Clinical Benefit Rate (objective responses plus stable disease rates) achieved with Pazopanib and its toxicity profile in this subgroup of patients


Condition Intervention Phase
Platinum-resistant Advanced Ovarian Cancer
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II, Multicenter, Prospective, Single Arm, Open Labeled Clinical Trial Investigating Pazopanib, a Multi-targeted Tyrosine Kinase Inhibitor (TKI) of VEGFR-1, -2, -3, PDGFR-α and -β and c-Kit in Patients With Platinum-resistant Advanced Ovarian Cancer.

Resource links provided by NLM:


Further study details as provided by Grupo Español de Investigación en Cáncer de Ovario:

Primary Outcome Measures:
  • The primary efficacy endpoint for this study is Clinical Benefit Rate [ Time Frame: average 30 months ] [ Designated as safety issue: No ]
    Clinical Benefit Rate defined as the percentage of patients with Complete Response plus Partial Response plus Stable Disease ≥ 8 weeks by RECIST v1.1


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: average 30 months ] [ Designated as safety issue: No ]
    Progression Free Survival (PFS) is defined as the time from the day of starting treatment to the first evidence of progression as defined by RECIST guidelines (v1.1) or death from any cause. If the patient does not have a documented date of progression or death, then PFS will be censored at the date of last adequate assessment.

  • Biological Response by CA-125 (GCIG Criteria) [ Time Frame: average 30 months ] [ Designated as safety issue: No ]
    CA-125 Testing: at pretreatment visit and during the treatment period and then every 3 months after discontinuation of treatment due to any reason (toxicity or patient will) until disease progression.

  • Overall Survival (OS) [ Time Frame: Average 3 years ] [ Designated as safety issue: No ]
    Overall Survival (OS) is defined as the time from first day of therapy to the date of death from any cause. For a patient who is alive at the time of the statistical analysis, the patient will be considered censored at the last date of known contact.

  • Biological progression-free interval (PFIBIO) [ Time Frame: average 30 months ] [ Designated as safety issue: No ]
    CA-125 Testing: at pretreatment visit and during the treatment period and then every 3 months after discontinuation of treatment due to any reason (toxicity or patient will) until disease progression. PFIBIO will be assessed according to the GCIG criteria

  • Quality of Life and symptom control [ Time Frame: average 5 years ] [ Designated as safety issue: No ]
    Quality of Life and symptom control will be assessed using EORTC QLQ-C30, QLQOV28, FACT/NCCN Ovarian Symptom Index (FOSI)

  • The safety and tolerability of study drug [ Time Frame: Average 5 years ] [ Designated as safety issue: Yes ]
    The safety and tolerability of study drugs are determined type, incidence, severity, timing, seriousness, and relatedness; of reported AEs, physical examinations, and laboratory tests. Toxicity will be graded and tabulated by the NCI-CTCAE v 3.0.

  • Descriptive pharmacodynamic profile [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    • the association between tumor PDGFRα expression (assessed by immunohistochemistry) and clinical outcomes (PFS, ORR, etc)
    • the relationship between serum VEGF/PDGF levels and clinical outcomes.


Enrollment: 28
Study Start Date: December 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental single arm
Single arm of pazopanib 800 mg (2x400mg) given as a single agent.
Drug: Pazopanib
800 mg (2x400mg) pazopanib per day should be taken orally without food at least one hour before or two hours after a meal until disease progression, the development of unacceptable toxicity, noncompliance, withdrawal of consent by the patient, or investigator decision.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up.
  2. Age ≥ 18 years
  3. The patient has histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal carcinoma, fallopian tube cancer
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  5. The patient has completed at least 4 CYCLES OF one and up to two platinum-containing regimens (involving cisplatin or carboplatin),for the management of this condition. Treatment may have included intraperitoneal therapy, consolidation or extended therapy administered after surgical or nonsurgical assessment.
  6. The patient must have a platinum-free interval of ≤ 6 months after the final dose of primary or subsequent platinum-based therapy.

    Patients must have platinum-resistant disease,(defined as progression within <6 months from completion of a minimum of 4 platinum therapy cycles. The date should be calculated from the last administered dose of platinum therapy.

  7. The patient has at least one unidimensionally measurable target lesion (≥ 20 mm or ≥ 10 mm by spiral computed tomography [CT] or magnetic resonance imaging [MRI]), as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines V 1.1.
  8. Previously archived tumor tissue from either the primary or metastatic tumor (paraffin block or 10 unstained slides) should be collected prior to administration of the first dose of study therapy and stored at a secure central laboratory.
  9. Adequate organ system function
  10. Women of child bearing potential should be using an effective method of contraception (complete abstinence, any intrauterine device (IUD) with published data showing that the lowest expected failure rate is < 1 % per year; or any other methods with published data showing that the lowest expected failure rate is less than 1 % per year) before entry into the study and throughout the same and for 6 months after ending the study. Women of childbearing potential must have a negative test serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta human chorionic gonadotropin [β-HCG]) within 7 days prior to randomization.
  11. Able to swallow oral compound.
  12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria:

  1. Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
  2. Previous treatment with >2 anticancer regimens for ovarian cancer
  3. Prior treatment with any antiangiogenic treatment (i.e. Bevacizumab)
  4. Patients with platinum-refractory disease defined as those patients progress during platinum-based therapy.
  5. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 6 months prior to first dose of study drug. Screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases.
  6. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:

    • Active peptic ulcer disease
    • Known intraluminal metastatic lesion/s with risk of bleeding
    • Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other gastrointestinal conditions with increased risk of perforation
    • History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.

      • active episodes of intestinal pseudo-obstruction
  7. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:

    • Malabsorption syndrome
    • Major resection of the stomach or small bowel.
    • Grade 3 diarrhoea
  8. Presence of uncontrolled infection.
  9. Corrected QT interval (QTc) > 480 msecs using Bazett's formula
  10. History of any one or more of the following cardiovascular conditions within the past 6 months:

    • Cardiac angioplasty or stenting
    • Myocardial infarction
    • Unstable angina
    • Coronary artery bypass graft surgery
    • Symptomatic peripheral vascular disease
    • Class II, III or IV congestive heart failure, as defined by the New York Heart Association (NYHA
  11. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg] instead an anti-hypertensive treatment.

    Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. BP must be assessed using the following recommendations:

    Once a patient has had an elevated blood pressure reading (> 140/80mmHg) this should be confirmed with another measurement, done locally if possible, either by the patients local doctor, or by home monitoring if available. Patients should continue to have their blood pressure monitored, at least weekly, until it becomes controlled (i.e. ≤ 140/80mmHg on 2 separate occasions, at least one week apart). Anti-hypertension medication changes, such as initiation of therapy, dose increases of existing therapies, or addition of other anti-hypertensive agents, should be done if the blood pressure remains high at 2 consecutive readings, at least 24 hours apart. Please, refer to guidance regarding the management of hypertension for the patient's local doctor for further information.

  12. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.

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

  13. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
  14. Prior minor surgery within 7 days prior to first dose of study drug
  15. Evidence of active bleeding or bleeding diathesis.
  16. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
  17. Hemoptysis within 6 weeks of first dose of study drug.
  18. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  19. Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
  20. Treatment with any of the following anti-cancer therapies:

    radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib

  21. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
  22. Women who are pregnant or breast-feeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01262014

Locations
Spain
H. Alcorcón
Alcorcón, Spain, 28922
H Vall d'Hebron
Barcelona, Spain, 08035
H. Clínic Barcelona
Barcelona, Spain, 08036
H. de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
H Reina Sofía Cordoba
Cordoba, Spain, 14004
Intitut Català d' Oncolgia L' Hospitalet
Hospitalet de LLobregat, Spain, 08907
H Ramón y Cajal de Madrid
Madrid, Spain, 28034
H Madrid. Centro Integral Oncológico Clara Campal
Madrid, Spain, 28250
HGU Gregorio Marañón
Madrid, Spain, 28007
Centro Oncológico MD Anderson Spain
Madrid, Spain, 28034
H de Sant Joan de Deu
Manresa, Spain, 08009
H Morales Meseguer
Murcia, Spain, 30008
H Son Llatzer
Palma de Mallorca, Spain, 07003
H Son Dureta
Palma de Mallorca, Spain, 07003
H. Parc Taulí
Sabadell, Spain, 08208
H Marqués de Valdecilla
Santander, Spain, 39008
H La Fe de Valencia
Valencia, Spain, 46009
Instituto Valenciano de Oncología
Valencia, Spain, 46009
H General de Valencia
Valencia, Spain, 46014
H Miguel Servet
Zaragoza, Spain, 50009
Sponsors and Collaborators
Grupo Español de Investigación en Cáncer de Ovario
Investigators
Study Chair: Ana Oaknin, MD H Vall d'Hebron
  More Information

No publications provided

Responsible Party: Dr. Andres Poveda, Grupo Español de Investigación en Cáncer de Ovario
ClinicalTrials.gov Identifier: NCT01262014     History of Changes
Other Study ID Numbers: GEICO-1002, 2010-020439-38
Study First Received: December 15, 2010
Last Updated: March 19, 2012
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ethics Committee

Keywords provided by Grupo Español de Investigación en Cáncer de Ovario:
platinum
resistant
advanced
ovarian
cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 22, 2014