E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Advanced Solid Tumors |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Non-small Cell Lung Cancer
Transitional Cell Carcinoma
Soft Tissue Sarcoma
Gastric/Esophageal Adenocarcinoma
Pancreatic Cancer Including Ampulla of Vater
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|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
Compare progression free survival (PFS) for brivanib versus placebo in subjects with advanced solid tumor with FGF-2 over-expression and who have obtained stable disease after 12 weeks of treatment with brivanib separately for each tumor type. |
|
E.2.2 | Secondary objectives of the trial |
• To determine the objective response rate (RR), duration of response (DOR), time to response (TTR), disease stabilization rate (DSR), and change in tumor size in FGF+ subjects
• To evaluate the safety of brivanib when given as mono-therapy
• To assess other biomarker studies and correlate with clinical outcomes (Collagen IV, VEGF, VEGFR-2, sFGF).
• To investigate associations between exposure to BMS-540215 and changes in biomarkers |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Target population
a) Able to comply with visits/procedures required by protocol.
b) Life expectancy at least 3 months.
c) Histologic or cytologic confirmed diagnosis of a solid tumor which is unresectable and locally advanced or metastatic in which no approved effective therapy exists or for subjects who are intolerable to such therapy. The initial enrollment will be limited to non-small cell lung cancer with the pathological classification of adenocarcinoma, gastric/esophageal adenocarcinoma only, soft tissue sarcoma, transitional cell carcinoma, and pancreatic cancer including ampulla of Vater tumors. Upon evaluation of preliminary data and recommendation from the Steering Committee, one or more of the following tumor types may be substituted: refractory prostate cancer, ovarian cancer, breast cancer, endometrial carcenoma, melanoma or head and neck cancer.
d) Measurable disease as defined in section 6.4.1.2.
e) Adequate tumor sample for FGF-2 assay as defined by historical pathology report
or local pathologist review (Appendix 6).
f) Adequate bone marrow, renal and hepatic function.
g) ECOG performance status 0 or 1 (Appendix 4).
h) Adequate recovery (baseline or Grade 1 for major toxicities) from recent therapy. At least 1 week must have elapsed from the time of a minor surgery, and at least 8 weeks for major surgery or 2 weeks for radiation therapy.
i) At least 3 weeks must have elapsed from the last dose of chemotherapy or targeted agents providing the subject has recovered from all toxicities. At least 8 weeks must have elapsed from the last dose of bevacizumab prior to beginning protocol therapy
2) Age and sex
a) Men and women age 18 or older. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study [and for up to 12 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. |
|
E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product.
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to investigational product administration.
d) Sexually active fertile men not using effective birth control if their partners are WOCBP (including up to 12 weeks after the last dose of investigational product).
2) Target Disease Exceptions
a) Subjects with known brain metastasis.
b) Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI.
c) Subjects with centrally cavitating lung lesions.
d) Subjects with predominantly centrally located lung lesions, adjacent to major blood vessels
3) Medical History and Concurrent Diseases
a) History of thrombo-embolic disease within the last six months requiring therapeutic anticoagulation as outlined in Section 5.3.1.3 of the protocol
b) Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder or cervical cancers) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period.
c) Subjects with history of poor wound healing or non healing ulcers
d) Uncontrolled or significant cardiovascular disease including:
• Myocardial infarction within 12 months
• Uncontrolled angina within 12 months
• Class III-IV New York Heart Association (NYHA) congestive heart failure (Appendix 7)
• Valvular heart disease CTCAE grade ≥ 2 (asymptomatic; moderate regurgitation
or stenosis by imaging)
• Uncontrolled hypertension (Systolic BP > 140 or diastolic BP > 90 mmHg for 24 hours) despite optimized anti-hypertensive therapy. BP must be ≤ 140/90 mmHg at screening.
• History of stroke, TIA, or other ischemic event
e) A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy
f) Any psychiatric or other disorders such as dementia that would prohibit the subjects from understanding or rendering informed consent or from fully complying with protocol treatment and follow-up
g) Inability to swallow tablets or untreated malabsorption syndrome
h) Inability to tolerate multiple blood sampling/or tolerate venous access
i) Any other medical, psychiatric, and/or social reason as determined by the Investigator
j) Subjects with a past history of clinically relevant tumor bleeding (ie ≥ 10 ml of blood
per day) or a predilection for bleeding from sites of tumor manifestation
4) Physical and Laboratory Test Findings
a) Absolute neutrophil counts < 1,500/mm3, platelet count < 80,000/mm3, or hemoglobin < 9 g/dl
b) Serum total bilirubin > 1.5 times the institutional upper limits of normal or ALT or AST > 2.5 times the institutional upper limits of normal (> 5 times IULN for subjects with documented liver metastases)
c) Serum creatinine > 1.5 times the institutional upper limits of normal
d) Hyponatremia with sodium < 125mEq/L
e) Albumin < 2.5 g/dl
5) Allergies and Adverse Drug Reactions
a) History of allergy to brivanib its drug class, or related compounds
6) Prohibited Treatments and/or Therapies
a) Exposure to any investigational drug within 4 weeks of enrollment
b) Other concurrent chemotherapy, hormonal therapy, immunotherapy regimens or radiotherapy, standard or investigational. Subjects may continue to receive hormone replacement therapy.
c) Prior exposure to brivanib
7) Other Exclusion Criteria
a) Prisoners or subjects who are involuntarily incarcerated
b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
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|
E.5 End points |
E.5.1 | Primary end point(s) |
Radiographic imaging and clinical evaluation will be used for tumor assessment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time Frame: every 6 weeks
|
|
E.5.2 | Secondary end point(s) |
Safety profiles [ Time Frame: ongoing throughout trial ]
Disease response rate [ Time Frame: determined June 2010 ]
Disease control rate [ Time Frame: determined June 2010 ]
Pharmacokinetics [ Time Frame: determined June 2010 ]
Pharmacodynamics [ Time Frame: determined June 2010 ]
Biomarkers [ Time Frame: determined June 2010 ] |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | 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) | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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 | No |
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 |
Argentina |
Belgium |
Canada |
France |
Germany |
Netherlands |
Poland |
United Kingdom |
United States |
|
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
| |
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |