E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant gastrointestinal stromal tumor (GIST), Metastatic Breast Cancer, Metastatic Renal Cell Cancer or Pancreatic Islet Cell Tumor. |
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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 | HLGT |
E.1.2 | Classification code | 10027655 |
E.1.2 | Term | Miscellaneous and site unspecified neoplasms malignant and unspecified |
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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 provide access to sunitinib treatment for subjects who have participated in previous “parent” sunitinib protocols and who have the potential as judged by the investigator to derive clinical benefit from sunitinib treatment.
•To assess the long-term safety and tolerability of sunitinib given in a continuous daily dose schedule (or of the combination of sunitinib and exemestane for subjects from parent protocol A6181108).
•To assess the duration of clinical benefit for subjects taking sunitinib (or the combination of sunitinib and exemestane for subjects from parent protocol A6181108).
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must have participated in a previous Pfizer Worldwide medical sponsored parent sunitinib study (as specified below) and, in the opinion of the parent study investigator are thought to have the potential to derive clinical benefit from continued treatment with sunitinib. • Protocol A6181107 subjects randomized to sunitinib who have completed treatment on the trial and who have shown clinical benefit. •Protocol A6181107 subjects randomized to capecitabine whose disease progressed on capecitabine during the study. •Protocol A6181108 subjects who have completed 2 years of treatment with sunitinib/exemestane and have shown clinical benefit. •Protocol A6181110 subjects who have completed one year of sunitinib treatment and have shown clinical benefit. •Protocol A6181111 subjects randomized to placebo whose disease has progressed while on placebo during the study. •Protocol A6181111 subjects who were randomized to either sunitinib or placebo, have completed the entire study treatment period, and have shown clinical benefit (sunitinib treated patients) or have stable disease (placebo patients) at the end of the trial. •Protocol A6181112 subjects randomized to sunitinib, who have completed the study and who have shown clinical benefit. 2. ECOG performance status 0, 1 or 2 3. Able to swallow an oral compound 4. Adequate organ function as defined by the following criteria at their last study visit on the previous parent protocol, or at the first visit for this study. Serum aspartate aminotransferase (AST; serum glutamate-oxalate transferase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase [SGPT]) ≤2.5 x upper limit of normal (ULN). If liver function abnormalities are due to underlying malignancy, then AST and ALT may be ≤5 x ULN. •Total serum bilirubin ≤1.5 x ULN •Prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 x ULN •Serum albumin >/=3.0 g/dL •Absolute neutrophil count (ANC) >/=1500/mL •Platelets >/=100,000/mL •Hemoglobin >/=9.0 g/dL •Serum creatinine ≤1.5 x ULN •Serum amylase and lipase ≤1.0 x ULN 5. Subjects must enroll as soon as possible from their End of Treatment/Withdrawal visit in the previous parent study, but in all cases within 4 weeks of this visit. 6. Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment. 7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures. 8. Male or female, 18 years of age or older. |
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E.4 | Principal exclusion criteria |
1.Current treatment in another clinical research trial. 2.Concurrent treatment with another anti-cancer drug except with exemestane as specified in this protocol. 3.Evidence of neurological signs/symptoms secondary to brain metastases, spinal cord compression, or new evidence of brain or leptomeningeal disease. 4.Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri. 5.Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other thromboembolic event. 6.Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively, prior to study drug administration. Potent CYP3A4 inhibitors and inducers will not be allowed as concomitant medications during the study. 7.Current treatment with therapeutic doses of anticoagulant (low dose Coumadin up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed). 8.Hypertension that cannot be controlled by medications (>150/100 mmHg despite optimal medical therapy). 9.Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication. 10.Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency syndrome (AIDS)-related illness. 11.Pregnancy or breastfeeding. Subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrollment. Male subjects must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. 12.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The objective of the study is to provide access to sunitinib treatment and assess long term safety, tolerability, and duration of clinical benefit, without any formal hypothesis testing; therefore, there is no formal primary endpoint. The following will be collected and reported on: •Duration of clinical benefit: For subjects who were taking sunitinib in the parent protocol, duration of clinical benefit is defined as the length of time subjects remain on sunitinib from the first day of treatment on the parent protocol (or the combination of sunitinib and exemestane for subjects in parent protocol A6181108) until the end of sunitinib treatment in this study. For subjects who were on placebo or a comparator drug in the parent study, duration of clinical benefit is defined as the length of time subjects are on sunitinib in this study. •Type, incidence, severity, timing, seriousness, and relatedness of Adverse Events In addition, for the purpose of calculating Overall Survival (OS) for the parent protocols, with the exception of A6181110, for which OS is not calculated, survival information will be collected and added to the Case Report Form (CRF) both during the term of this study, as well as after the subject terminates treatment in this study.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 83 |
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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Subjects should continue to be evaluated for 28 calendar days after the last dose of study drug. During the post-treatment follow-up visit, the following procedures should be performed:
•Assessment of adverse events •Assessment of concomitant medications and treatments |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |