Feasibility Study of Pazopanib in Combination With Chemotherapy in Gynaecological Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00561795
First received: November 19, 2007
Last updated: March 15, 2012
Last verified: March 2011
  Purpose

This is an open-label, two-arm, multicenter feasibility study to evaluate the safety and tolerability of pazopanib in combination with carboplatin and paclitaxel in female subjects with newly diagnosed advanced gynaecological tumors. Subjects will have received no prior therapy for their disease. A minimum of 12 and a maximum of 46 subjects will be enrolled. Dose schemas for each study arm are described in the protocol. For each arm, six subjects will be evaluated in treatment cohorts, which will be expanded to 20 subjects if initial toxicity is acceptable. Overall safety and tolerability of the regimen will be based on dose limiting toxicities, adverse events, and percentage of subjects that complete 6 courses of study treatment. Antitumor activity will be assessed using RECIST criteria and cancer antigen 125 (CA-125) responses.


Condition Intervention Phase
Primary Peritoneal Carcinoma
Tumor
Epithelial Ovarian Cancer
Uterine Disease
Cervix Diseases
Neoplasms, Ovarian
Cancer
Drug: pazopanib (GW786034)
Drug: carboplatin
Drug: paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label, Multicenter, Two-Arm, Feasibility Study of Pazopanib, Carboplatin, and Paclitaxel in Women With Newly Diagnosed, Previously Untreated, Gynaecological Tumors

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants Experiencing Serious Adverse Events and Non-serious Adverse Events [ Time Frame: Baseline to End of Study (up to a year) ] [ Designated as safety issue: No ]
    Safety and tolerability were measured by the number of participants with serious adverse events and non-serious adverse events. See the "Adverse Event" section of the results record for additional details and data.


Secondary Outcome Measures:
  • Overall Response [ Time Frame: Baseline until either response or progression (up to 2 years) ] [ Designated as safety issue: No ]
    Although the study protocol specified several efficacy analyses, due to poor tolerability of the combination regimen and the consequent early withdrawal of most participants, which led to a small sample size, efficacy analyses were not performed. Overall response is defined as the number of participants with CR or PR per Response Evaluation Criteria In Solid Tumors (RECIST): CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum.

  • Cancer Antigen (CA-125) Response [ Time Frame: Baseline until response (up to 2 years) ] [ Designated as safety issue: No ]
    Defined as the number of participants who achieved a confirmed CA-125 response, which is defined as at least a 50% reduction in CA-125 levels from a pre-treatment sample.

  • 18-week Progression Free Survival [ Time Frame: Baseline to Week 18 ] [ Designated as safety issue: No ]
    Defined as the number participants who have not had radiological disease progression per RECIST, confirmed CA-125 progression, or death due to any cause by the end of 18 weeks.


Enrollment: 12
Study Start Date: September 2007
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Oral Pazopanib 800 mg once a day+ carboplatin area under the concentration-time curve (AUC) 5 intravenous (IV) over 1 hour every 3 weeks + paclitaxel 175 mg/m^2 IV over three hours day one q 3 weeks for six cycles
Drug: pazopanib (GW786034)
800 mg orally once a day for 6 cycles
Other Name: Pazopanib (GW786034)
Drug: carboplatin
IV over one hour every 3 weeks of 6 cycles
Drug: paclitaxel
IV 175 mg/m^2 given over 3 hours on day one of a 21 day cycle for six cycles
Experimental: Arm B
Oral Pazopanib 800 mg once a day+ carboplatin AUC 6 IV over 1 hour every 3 weeks + paclitaxel 175 mg/m^2 IV over three hours day one q 3 weeks for six cycles
Drug: pazopanib (GW786034)
800 mg orally once a day for 6 cycles
Other Name: Pazopanib (GW786034)
Drug: carboplatin
IV over one hour every 3 weeks of 6 cycles
Drug: paclitaxel
IV 175 mg/m^2 given over 3 hours on day one of a 21 day cycle for six cycles

  Eligibility

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

Inclusion criteria:

  • Inclusion Criteria
  • A subject will be considered eligible for inclusion in this study only if all of the following criteria are met:
  • 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.
  • Procedures conducted as a part of routine clinical management of the subject (e.g., blood count, imaging study) and obtained prior to signed informed consent may be utilized for Screening or Baseline purposes provided these tests are obtained as specified in the protocol).
  • Female subjects ≥18 years of age with newly diagnosed advanced gynaecological malignancies for whom carboplatin and paclitaxel based chemotherapy is indicated. Patients may have surgery to debulk or resect disease but may not have received chemotherapy or radiotherapy.
  • Histological confirmation of the following: epithelial ovarian cancer, endometrial carcinoma, uterine sarcoma, mixed Müllerian tumour, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma or vulvar carcinoma.
  • Performance status must be ECOG 0 1.
  • Adequate organ system function as defined in Table 6
  • Table 6 Definitions for Adequate Organ Function
  • System (Laboratory Values)
  • Hematologic:
  • Absolute neutrophil count (ANC) (≥ 1.5 X 109/L)
  • Hemoglobin1 (≥9 g/dL)
  • Platelets (≥100 X 109/L)
  • International normalized ratio (INR)(≤ 1.2 X upper limit of normal (ULN))
  • Partial thromboplastin time (PTT) (≤1.2 X ULN)
  • Hepatic:

p Total bilirubin (≤1.5 X upper limit of normal (ULN))

  • AST and ALT (≤ 2.5 X ULN)
  • Renal:
  • Serum Creatinine (≤ 1.5 mg/dL)
  • Or, if serum creatinine >1.5 mg/dL, (≥ 50 mL/min)
  • Calculated creatinine clearance
  • Urine Protein to Creatinine Ratio2 (<1)
  • Patients may not have had a transfusion within 7 days of screening assessment.
  • If UPC ≥1, then a 24-hour urine protein must be assessed. Patients must have a 24-hour urine protein value <1g to be eligible.
  • Measurable or non-measurable disease.
  • A female subject is eligible to enter and participate in the study if she is:
  • Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any woman who:
  • Has had a hysterectomy, or
  • Has had a bilateral oophorectomy (ovariectomy), or
  • Has had a bilateral tubal ligation, or
  • Is post-menopausal
  • Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL (<140 pmol/L).
  • Subjects who are using hormone replacement therapy and whose menopausal status is in doubt will be required to use a highly effective method of contraception (as outlined in this inclusion criterion) if they wish to continue their HRT during the study. Otherwise, these subjects must discontinue HRT prior to study enrollment to allow confirmation of post menopausal status. For most forms of HRT, at least 2-4 weeks must elapse between the cessation of HRT and determination of menopausal status; length of this interval depends on the type and dosage of HRT. Following confirmation of post menopausal status, these subjects can resume HRT during the study without use of contraception.
  • Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow:
  • An intrauterine device with a documented failure rate of less than 1% per year.
  • Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
  • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
  • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide).

Note: Oral contraceptives are not reliable due to potential drug-drug interactions.

  • Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
  • Recovered from the effects of surgery.
  • Prior radiotherapy is permissible, provided at least 4 weeks have elapsed since the last treatment to allow for full bone marrow recovery.

Exclusion Criteria

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • Prior use of anticancer therapy (except cytoreductive surgery [debulking]) for their cancer.
  • Presence of bulky, residual, squamous cell tumors.
  • Is unable to discontinue prohibited medications, as listed in Section 8.2 for 14 days or five half-lives of a drug prior to Visit 1 and for the duration of the study.
  • Clinically significant gastrointestinal abnormalities which might interfere with oral dosing, including but not limited to:
  • Malabsorption syndrome
  • Major resection of the stomach or small bowel that could affect the absorption of study drug
  • Active peptic ulcer disease
  • Inflammatory bowel disease
  • Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.
  • Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy).
  • Inadequately controlled hypertension (systolic blood pressure [SBP] of ≥140 mmHg, or diastolic blood pressure [DBP] of ≥ 90 mmHg). Initiation or adjustment of blood pressure medication is permitted prior to study entry provided the subject has 2 consecutive blood pressure readings less than 140/90 mmHg, each separated by a minimum of 24 hours. These readings need to be collected prior to the first dose.
  • Hemoptysis within four weeks prior to first dose of study drug.
  • Prior major trauma within 14 days prior to first dose of study drug.
  • Prior major surgery within 14 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. In the case of surgery involving the bowel, subjects must be 28 days post-surgery to be eligible.
  • Prolongation of corrected QT interval (QTc) > 480 msecs.
  • History of any one of more of the following cardiovascular conditions within the past 6 months:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Unstable angina
  • Symptomatic peripheral vascular disease
  • Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA) [See History of cerebrovascular accident (CVA), 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-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible.
  • Metastatic disease to the brain or leptomeninges.
  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: NCT00561795

Locations
France
GSK Investigational Site
Lyon Cedex 08, France, 69373
GSK Investigational Site
Strasbourg, France, 67085
Germany
GSK Investigational Site
Marburg, Hessen, Germany, 35043
GSK Investigational Site
Wiesbaden, Hessen, Germany, 65199
GSK Investigational Site
Essen, Nordrhein-westfalen, Germany, 45122
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00561795     History of Changes
Other Study ID Numbers: VEG110190
Study First Received: November 19, 2007
Results First Received: November 19, 2009
Last Updated: March 15, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
AGO
Advanced,
Gynaecologic cancer(s),
Genetics
GW786034,
Pazopanib,

Additional relevant MeSH terms:
Uterine Diseases
Uterine Cervical Diseases
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Endocrine System Diseases
Gonadal Disorders
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Histologic Type
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014