Feasibility Study of Pazopanib in Combination With Chemotherapy in Gynaecological Tumors

NCT00561795 | Completed Phase 2 Results

• 1 other identifier: VEG110190
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 5

Brief Summary

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.

Conditions

Primary Peritoneal Carcinoma; Tumor; Epithelial Ovarian Cancer; Uterine Disease; Cervix Diseases; Neoplasms, Ovarian; Cancer

Keywords

AGO; Advanced,; Gynaecologic cancer(s),; Genetics; GW786034,; Pazopanib,

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Serious Adverse Events and Non-serious Adverse Events

  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.

  Baseline to End of Study (up to a year)

Secondary Outcomes (3)

• Overall Response

  Baseline until either response or progression (up to 2 years)

• Cancer Antigen (CA-125) Response

  Baseline until response (up to 2 years)

• 18-week Progression Free Survival

  Baseline to Week 18

Study Arms (2)

Arm A

EXPERIMENTAL

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); Drug: carboplatin; Drug: paclitaxel

Arm B

EXPERIMENTAL

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); Drug: carboplatin; Drug: paclitaxel

Interventions

pazopanib (GW786034) DRUG

800 mg orally once a day for 6 cycles

Arm A; Arm B

carboplatin DRUG

IV over one hour every 3 weeks of 6 cycles

Arm A; Arm B

paclitaxel DRUG

IV 175 mg/m\^2 given over 3 hours on day one of a 21 day cycle for six cycles

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (5)

GSK Investigational Site

Lyon, 69373, France

Location

GSK Investigational Site

Strasbourg, 67085, France

Location

GSK Investigational Site

Marburg, Hesse, 35043, Germany

Location

GSK Investigational Site

Wiesbaden, Hesse, 65199, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Ovarian Epithelial; Uterine Diseases; Uterine Cervical Diseases; Ovarian Neoplasms

Interventions

pazopanib; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

As defined in the protocol, a review of the safety data in Arm A showed that \>=2 participants in each regimen of Arm A experienced dose-limiting toxicities. Thus the study was closed to further enrollment and no participants were enrolled into Arm B.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2007
• First Posted: November 21, 2007
• Study Start: September 1, 2007
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: March 22, 2012
• Results First Posted: December 7, 2010

Record last verified: 2011-03

Locations

DE (3); FR (2)