Phase II Study of Brivanib (BMS-582664) to Treat Multiple Tumor Types

Phase 1

• Conditions: Subjects with Advanced Solid Tumors; MedDRA version: 14.0Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-000087-16-BE
• Lead Sponsor: Bristol-Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-08-13
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
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) yes
F.1.3.1 Number of subjects for this age range

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 Ther

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified