A Phase II, Open-Label, Randomized, Multicenter Trial of Pazopanib (GW786034) in Combination with Lapatinib (GW572016) Compared to Pazopanib Monotherapy and Lapatinib Monotherapy in Subjects with FIGO Stage IVB or Recurrent or Persistent Cervical Cancer with Zero or One Prior Chemotherapy Regimen for Advanced/Recurrent Disease
- Conditions
- Cervical CancerMedDRA version: 14.1Level: PTClassification code 10008348Term: Cervix carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2006-000236-27-IT
- Lead Sponsor
- GlaxoSmithKline R&D Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 180
1. Signed, written informed consent prior to performing any study-related procedures 2. Female subjects major or equal to 18 years of age 3. Life expectancy of at least 12 weeks 4. ECOG status of 0 or 1. 5. Histologically confirmed FIGO Stage IVB, or recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy 6. Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be >20 mm when measured by conventional techniques, including palpitation, plain x-ray, CT and MRI, or > 10 mm when measured by spiral CT. 7. At least one 'target lesion' to be used to assess response as defined by Response Evaluation Criteria in Solid Tumors (RECIST; Terasse, 2000). Tumors within a previously irradiated field will be designated as 'non-target' lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy. 8. Received 0 or 1 prior chemotherapy regimen for metastatic disease. ? Note: Chemotherapy given in combination with radiation therapy as a radiosensitizer does not count toward this prior therapy limit 9. Recovered from the effects of surgery or chemotherapy. At least three weeks must have elapsed from the last administration of chemotherapy. 10. Adequate organ and bone marrow function as defined in Table 2. 11. Ability to swallow and retain oral medication. 12. A female is eligible to enter and participate in this study if she is of: ? Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: o A hysterectomy o A bilateral oophorectomy (ovariectomy) o A bilateral tubal ligation o Is post-menopausal (total cessation of menses for at least 1 year) ? Childbearing potential, has 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 follows: o An intrauterine device with a documented failure rate of less than 1% per year. o Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female. o Complete abstinence from sexual intercourse for 14 days before exposure to investigation product, through the clinical trial, and for at least 21 days after the last dose of investigational product. o 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 interaction. 13. Must complete all screening assessments as outlined in the protocol. Note: Subjects must provide written informed consent prior to performance of any study-specific procedures or assessments (including initial diagnosis) and are willing to comply with treatment and follow-up.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this
1. Neuroendocrine or small cell carcinoma of the cervix. 2. Prior use of any biologic therapy with VEGF, VEGFR, or ErbB1/ErbB2 inhibitors. 3. Concurrent cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, and tumor embolization). 4. Concurrent treatment with an investigational agent or participation in another clinical trial. 5. Use of an investigational anti-cancer drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of study medication. 6. Has taken or is taking prohibited medications listed in the protocol. 7. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study. 8. History of another malignancy. Note: Patients who have had another malignancy and have been disease-free for 5 years, or patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. 9. History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis. Routine screening with CNS imaging studies (computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if clinically indicated. 10. Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate progression-free survival (PFS) of the combination regimen versus each of the monotherapy arms in subjects with FIGO Stage IVB, or recurrent or persistent cervical cancer who have had zero or one prior chemotherapy regimen for advanced disease.;Secondary Objective: ? To evaluate overall survival, the anti-tumor activity in terms of clinical benefit (complete or partial response or durable stable disease), response rate (defined as the percentage of patients achieving either a complete or partial tumor response per RECIST criteria.), time to response and duration of response for each treatment arm. ? To evaluate the influence of ErbB1 and ErbB2 gene amplification on the clinical efficacy of pazopanib, lapatinib, and the combination of pazopanib and lapatinib. ? Evaluate the safety and tolerability of the combination of pazopanib and lapatinib compared to pazopanib monotherapy and lapatinib monotherapy in this subject population.;Primary end point(s): ? Progression Free Survival
- Secondary Outcome Measures
Name Time Method