PHASE 1 SAFETY AND TOLERABILITY STUDY OF FIGITUMUMAB COMBINED WITH PEGVISOMANT IN PATIENTS WITH ADVANCED SOLID TUMORS

• Conditions: Advanced Solid Tumors; MedDRA version: 9.1Level: LLTClassification code 10049280Term: Solid tumour

• Registration Number: EUCTR2009-012769-74-FI
• Lead Sponsor: Pfizer Inc., 235 East 42nd Street, New York, NY 110017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-15
• Last Update Posted: 14 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study.
Unless compelling reason(s) to be agreed upon and documented by the investigator and sponsor, subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Patients must be =18 years of age.
Exception: Patients =10 years of age with a diagnosis of advanced sarcoma will be included in the Sarcoma Expansion Cohort.
2. Histologic verification of malignancy at original diagnosis.
3. Patients =18 years of age with advanced solid tumors for which the combination of figitumumab and pegvisomant are reasonable treatment options.
4. Patients =10 years of age with a diagnosis of Ewing’s sarcoma family of tumors or
other advanced sarcoma for which there is no available curative therapy or therapy
proven to prolong survival with an acceptable quality of life will be included in the
Sarcoma Expansion Cohort.
5. ECOG 0 1 (or Lansky =70% for patients <18 years of age).
6. Adequate recovery from major surgery prior to study treatment.
7. Patients must have fully recovered from the acute toxic effects of prior therapy.
8. Adequate bone marrow function defined as:
• Platelet count =75,000/µL (platelet transfusion allowed);
• Hemoglobin =8.0 gm/dL (RBC transfusion allowed);
• Peripheral absolute neutrophil count (ANC) =1000/µL without growth factor support during the 72 hours prior to enrollment.
9. Adequate renal function defined as creatinine =1.5 x ULN (upper limit of normal).
10. Adequate liver function defined as:
• Total bilirubin =1.5 x ULN (except patients with liver metastasis or Gilbert’s syndrome);
• Serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) =2.5 x ULN (=5 x ULN if liver function abnormalities are attributed to underlying malignancy);
11. Sexually active female patients must be either postmenopausal or, if of childbearing age, must be surgically sterile or must agree to use effective contraception during the period of therapy and up to 5 months after the last dose of figitumumab. Acceptable contraception includes, but is not limited to: oral hormone therapy, partner vasectomy, or double barrier contraception (which is defined as a male condom plus spermicide in combination with either a female condom, or diaphragm, or cervical cap or intrauterine device). The following forms are not acceptable: withdrawal method, rhythm method, spermicide, barrier sponge with or without spermicide. Within these limits, the specific form of contraception employed is left to the discretion of the subject, principal Investigator, and/or primary care physician. Sexually active male patients must be sterile or must agree to use effective contraception during the period of therapy and up to 5 months after the last dose of figitumumab.
12. All patients must sign and date a written voluntary informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Parental or legal guardian consent or patient assent/parent permission will be required for minors as per institutional practice;
13. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

This study can fulfill its objectives only if appropriate subjects are enrolled. The following eligibility criteria are

Exclusion Criteria

Unless compelling reason(s) to be agreed upon and documented by the investigator and sponsor, subjects presenting with any of the following will not be included in the study:
1. Concurrent treatment with any anti tumor agents.
2. Participation in other studies within 28 days before the current study begins and/or during study.
3. Concurrent therapy with a somatostatin analogue.
4. CNS tumors or symptomatic brain metastases.
5. Pregnant or breastfeeding females.
6. Significant active cardiac disease including:
• Left ventricular ejection fraction <50%;
• Uncontrolled hypertension (systolic BP >160 mmHg and/or disastolic BP >100 mmHg);
• Any ventricular arrhythmia;
• Mitral valve regurgitation > trivial as determined by Doppler Echocardiogram.
7. Subjects receiving or are likely to require corticosteroids at doses higher than physiologic replacement (ie, Prednisone equivalent 5 mg/day) or other immunosuppressive therapy during study participation.
8. Active infection, including hepatitis B or C, or receiving antiretroviral therapy for HIV disease.
9. Glycosylated hemoglobin (HgbA1c) =7%.
10. History of diabetes mellitus.
11. Concurrent treatment with medications indicated for the treatment of diabetes mellitus.
12. History of allergic reaction to IgGs.
13. History of hypersensitivity to any pegvisomant component, including latex. The stopper on the vial of pegvisomant contains latex.
14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for study entry.
15. Subjects who have been admitted to an institution by virtue of an order issued by either the judicial or administrative authorities.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of figitumumab plus pegvisomant in<br>patients with advanced solid tumors.;Primary end point(s): Safety and tolerability of figitumumab and pegvisomant (Adverse events per CTCAE v3.0);Secondary Objective: To evaluate circulating concentrations of IGF-I during therapy with figitumumab<br>and pegvisomant;<br>? To evaluate the pharmacokinetics of figitumumab and pegvisomant in<br>combination;<br>? To explore screening, cycle 1 day 8 and cycle 3 day 8 glucose tolerance;<br>? To monitor any anti-drug antibody (ADA) response to figitumumab;<br>? To document any anti-tumor activity of figitumumab plus pegvisomant.<br>Additionally, blood samples will be collected for the measurement of IGF-1R related<br>biomarkers, including IGF-1 (free and total), IGF-2, IGFBP1-6, insulin and C-peptide.<br>The analysis of these biomarkers will be exploratory using descriptive statistics.