E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with FIGO Stage IVB or recurrent or persistent cervical cancer with zero or one prior chemotherapy regimen for advanced/recurrent disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008229 |
E.1.2 | Term | Cervical cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed, written informed consent prior to performing any study-related procedures 2. Female subjects 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. 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 protocol. 11. Ability to swallow and retain oral medication. 12. A female is eligible to enter and participate in this study if she meets the criteria outlined in the protocol. 13. Must complete all screening assessments as outlined in the protocol. |
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E.4 | Principal exclusion criteria |
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. 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. 11. Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal condition increasing the risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to beginning therapy. 12. Presence of uncontrolled infection. 13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib. 14. Corrected QT interval (QTc) prolongation defined as QTc interval > 470 msecs. 15. History of any one of the cardiac conditions listed in the protocol within the past 6 months. 16. History of cerebrovascular accident or pulmonary embolus within the past 6 months. 17. Has Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (See Appendix 6) 18. Poorly controlled hypertension (systolic blood pressure (SBP) of 140mmHg, or diastolic blood pressure (DBP) of 90mmHg). 19. History of untreated deep venous thrombosis (DVT) within the past 6 months (e.g. calf vein thrombosis). 20. Presence of any non-healing, non-tumor related wound, fracture, or ulcer, or the presence of symptomatic peripheral vascular disease. 21. Subjects with bilateral hydronepherosis which cannot be alleviated by ureteral stents or percutaneous drainage. 22. Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to beginning therapy, or anticipation of the need for a major surgical procedure during the course of the study; minor surgical procedures such as fine needle aspiration or core biopsy within 1 week prior to beginning therapy are also excluded. 23. Unable to swallow and retain orally administered medication. 24. Pregnant or lactating female.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Definition of end of trial is the last visit of the last subject undergoing the trial, as described in the protocol |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |