Dose-Escalation Study to Evaluate the Savety and Tolerability of SCH 717454 in Combination with Different Treatment Regimens in Subjects with Advanced Solid Tumors (Phase 1b/2; Protocol No. P04722) - N/A
- Conditions
- Colorectal Adenocarcinoma, Non-small Cell Lung Cancer, Gastric Adenocarcinoma, Her2+ Breast Cancer, Renal Cell Cancer, Pancreatic AdenocarcinomaMedDRA version: 12.0 Level: LLT Classification code 10001150 Term: Adenocarcinoma gastricMedDRA version: 12.0 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancerMedDRA version: 12.0 Level: LLT Classification code 10038407 Term: Renal cell cancerMedDRA version: 12.0 Level: LLT Classification code 10051971 Term: Pancreatic adenocarcinomaMedDRA version: 12.0 Level: PT Classification code 10052360 Term: <Manually entered code. Term in E.1.1>MedDRA version: 12.0 Level: PT Classification code 10061873 Term: <Manually entered code. Term in E.1.1>
- Registration Number
- EUCTR2009-011101-16-AT
- Lead Sponsor
- Schering-Plough Research Institute, A Division of Schering Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 250
1. Subject must be =18 years of age. A subject may be of either sex & of any race/ethnicity
2. Part 1: Subject must have a histologically or cytologically confirmed advanced malignant solid tumor
Part 2: Subject must have a histologically or cytologically confirmed, with measurable disease (as defined by RECIST), advanced, malignant solid tumor type as specified below for which treatment in the given regimen is appropriate:
Regimen A: Colorectal Adenocarcinoma
Regimen B: Non-small Cell Lung Cancer
Regimen C: Gastric Adenocarcinoma
Regimen D: Her2+ Breast Cancer
Regimen E: Renal Cell Cancer
Regimen F: Pancreatic Adenocarcinoma
3. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of =2
4. Subject must have adequate organ function within 3 wks prior to 1st study drug administration as evidenced by:
a) Absolute neutrophil count =1.5 x 10 to the 9th power /L
b) Hemoglobin =90 g/L (=80 g/L for subjects w/renal cell carcinoma)
c) Platelet count =100 x 10 to the 9th power/L
d) Serum creatinine =1.5 x upper limit of normal (ULN) or a calculated creatinine clearance >60 mL/min
e) Total bilirubin <1.5 x ULN, except for subjects w/Gilbert’s disease,
f) Alkaline phosphatase, aspartate aminotransferase (AST)/serum glutamic-oxalacetic transaminase (SGOT) & alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <3 x ULN, or, in the presence of documented liver metastases, =5 x ULN
5.(Only subjects assigned to receive Epirubicin [Regimen C]): Each subject must have a left ventricular ejection fraction (LVEF) of =50% by Multi Gated Acquisition Scan (MUGA) or echocardiogram
6. Subject must be able to adhere to dose & visit schedules
7. Female subject (& male subject whose female partner also provides written informed consent to provide information regarding pregnancy) of childbearing potential, must agree to use a medically accepted method of contraception, or abstain from sexual intercourse, during Screening, while receiving protocol-specified medication, & for 2 months after stopping the medication. Females who are not currently sexually active must also consent to use one of these accepted methods of contraception should they become sexually active while participating in the study. Medically accepted methods of contraception include: systemic hormonal contraceptive & surgical sterilization (eg, hysterectomy or tubal ligation). Condoms (male & female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, & medically prescribed intrauterine devices may be acceptable according to local regulations
Note: Vasectomy of the partner is not considered sufficient contraception, & one of the methods listed above must be used. A male subject must agree to use a medically accepted method of contraception (see above) or abstain from sexual intercourse during the trial & for 2 months after stopping the medication. Postmenopausal women are not required to use contraception. Postmenopausal is defined as at least 12 consecutive months without a spontaneous menstrual period
8. To participate in the pharmacogenomic analysis, the subject must be
1. Subject must not have known treated or untreated leptomeningeal metastasis or a metastatic central nervous system lesion. Subjects w/a clinical history of central nervous system metastases or cord compression may be eligible, provided they have been definitively treated & are clinically stable, after discussion w/sponsor
2. Subject must not have a history (w/in 5 yrs prior to first study drug administration) of another malignancy excluding adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin or carcinoma in situ of the cervix or other adequately treated malignancy for which the subject has been disease free for =5 yrs)
3. Subject must not have received any treatment listed in the Table stated in Protocol syopsis more recently than the indicated washout period prior to Day 1 Cycle 1
4. A subject must not continue to receive any treatment listed in the Table stated in Protocol synopsis during the current trial
5. Subject must not have received prior therapy w/any anti-IGF-1R monoclonal antibody
6. Subject must not have received radiation therapy w/in 2 wk prior to 1st study drug administration
7. Subject must not have received radiation therapy to >25% of his/her total bone marrow during his/her lifetime
8. Subject must not have undergone major surgery w/in 3 weeks prior to first study drug administration
9. Subject must not have known human immunodeficiency virus (HIV) infection or a known HIV-related malignancy. If the investigator is suspicious that a subject has one of these diseases, they should test to confirm prior to Day 1 Cycle 1
10.Subject must not have known active hepatitis B or C. If the investigator is suspicious that a subject has one of these diseases, they should test to confirm prior to Day 1 Cycle 1
11. Subject must not have any serious or uncontrolled infection
12. Subject must not have uncontrolled diabetes mellitus, defined as a hemoglobin A1C of =7.5% at Screening in a subject w/known diabetes mellitus (subjects w/elevated glucose values at Screening should be evaluated for diabetes mellitus)
13. Subject must not have had any of the following w/in 6 months prior to 1st study drug administration: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, clinically significant cardiac dysrhythmia or clinically significant ECG abnormality, cerebrovascular accident or transient ischemic attack, or seizure disorder
14. Subject must not have persistent, unresolved CTC for AEs (CTCAE) Grade =2 drug-related toxicity (except alopecia, erectile impotence, tinnitus, hot flashes, & loss of libido) associated w/previous treatment (inclusion of subjects w/persistent neuropathy or hearing loss Grade =2 due to previous treatment require discussion with the sponsor)
15. Subject must not be participating in any other clinical study w/a potentially therapeutic agent or must not have received another investigational product w/in 21 days prior to Day 1 Cycle 1
16. Subject must not have any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participati
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: Evaluate AE profile, PK parameters, determine incidence of anti-SCH 717454 antibodies, and evaluate peripheral blood levels of IGF-I, IGF-II, IGFBP-2.;<br> Main Objective: Part 1-Determine a safe and well-tolerated dose of SCH 717454 in combination with different treatment regimens in subjects with solid tumors.<br><br> Part 2-Determine tumor response rate for SCH 717454 as defined by RECIST, in combination with different treatment regimens.<br> ;<br> Primary end point(s): Determine a safe and generally well-tolerated dose of SCH 717454 to be administered in combination with other treatment agents in subjects with advanced solid tumors. Summaries of dose limiting toxicities (DLTs), all adverse events (AEs), and laboratory results will be provided for the MAD<br>
- Secondary Outcome Measures
Name Time Method