Phase I Study of IMC-A12 (NSC# 742460) in Combination With Temsirolimus CCI-779 (NSC# 683864) in Patients With Advanced Cancers
18 Years
N/A
Both
Malignant Neoplasm
Trial Information
Phase I Study of IMC-A12 (NSC# 742460) in Combination With Temsirolimus CCI-779 (NSC# 683864) in Patients With Advanced Cancers
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of anti-IGF-1R recombinant monoclonal antibody
IMC-A12 in combination with temsirolimus in patients with locally advanced or metastatic
cancer.
II. To determine the maximum tolerated dose of this regimen in these patients. III. To
evaluate the biologic effect of this regimen on expression/phosphorylation of potential
markers of response in patients with disease amenable to biopsy.
IV. To assess tumor metabolism as assessed by PET scan.
SECONDARY OBJECTIVE:
I. To report the clinical tumor response in patients treated with this regimen.
OUTLINE: This is a multicenter study.
Dose escalation phase: Patients receive temsirolimus IV over 30 minutes and cixutumumab IV
over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity. After the maximum tolerated dose (MTD) is
determined, subsequent patients are enrolled into the MTD expansion cohort.
MTD expansion cohort: Patients are assigned to 1 of 3 treatment groups.
Group A: Patients receive temsirolimus IV over 30 minutes on days 15 and 22 for course 1 and
on days 1, 8, 15, and 22 for all subsequent courses. Patients also receive cixutumumab IV
over 60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
Group B: Patients receive cixutumumab IV over 60 minutes on days 15 and 22 for course 1 and
on days 1, 8, 15, and 22 for all subsequent courses. Patients also receive temsirolimus IV
over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.
Group C: Patients receive temsirolimus IV over 30 minutes and cixutumumab IV over 60 minutes
on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.
Patients undergo blood sample collection periodically for pharmacodynamic studies. Patients
enrolled in the MTD expansion cohort also undergo tumor biopsy and PET scans periodically.
Blood and tumor tissue samples are analyzed for molecular biomarker alterations in the
IGF-1R-mTOR signaling pathway (including, but not limited to, AKT, pAKT, IGF-1R, pIGF-1R,
IRS-1, PTEN, IRS-1, VEGFR1, VEGFR2, and CD31) by reverse phase protein arrays,
immunohistochemistry, and ELISA assays.
After completion of study treatment, patients are followed within 30 days.
Inclusion Criteria
Criteria:
- Diagnosis of locally advanced or metastatic cancer
- No highly aggressive lymphoma (i.e., Burkitt lymphoma)
- Disease amenable to biopsy (for patients enrolled in the maximum tolerated dose [MTD]
expansion cohort)
- History of brain metastasis allowed provided the brain metastases were previously
treated with surgery or radiotherapy and the patient has been free from
symptoms/signs and has been off steroids for >= 3 months
- ECOG performance status 0-1
- Life expectancy > 3 months
- ANC >= 1,500/mL
- Platelet count >= 100,000/mL
- Creatinine =< 2 times upper limit of normal (ULN)
- Total bilirubin =< 1.5 times ULN
- AST and/or ALT =< 5 times ULN
- INR =< 1.5
- PTT =< 5 seconds above ULN
- Fasting blood sugar =< 120 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to, during, and for 3 months
after completion of study treatment
- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within the past 28 days
- No concurrent uncontrolled illness including, but not limited to, active infection
requiring hospitalization
- No history of cerebrovascular accident, myocardial infarction, or unstable angina
within the past 6 months
- No New York Heart Association class III or IV congestive heart failure
- No uncontrolled hyperlipidemia (i.e., cholesterol > 300 mg/dL and triglycerides 2.5
times ULN despite lipid lowering agents)
- No history of hypersensitivity to monoclonal antibody treatment or immunosuppressant
agents
- Recovered from prior therapy
- At least 4 weeks since prior chemotherapy, other investigational therapy, biological
therapy, targeted agents, or radiotherapy
- Prior palliative low-dose radiotherapy to the limbs is allowed within the past 4
weeks provided the pelvis, sternum, scapulae vertebrae, or skull were not included in
the radiotherapy field
- At least 6 weeks since prior monoclonal antibodies
- At least 2 weeks since prior hormonal therapy
- At least 5 half-lives since prior and no concurrent drugs that are strong P450 CYP3A4
inhibitors or inducers
- Concurrent prednisone or hydrocortisone allowed in patients who have undergone an
adrenalectomy
- No other concurrent investigational agents
- No other concurrent anticancer therapy, including radiotherapy
- Concurrent antidiabetic treatment (e.g., oral hypoglycemic agents and/or insulin)
allowed provided baseline glucose is normal (for patients enrolled in the MTD
expansion cohort)
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
MTD of combination of cixutumumab and temsirolimus defined as the highest dose level at which no more than 1 of 6 evaluable patients has had a dose-limiting toxicities
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Aung Naing
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00282
NCT ID:
NCT00678769
Start Date:
May 2008
Completion Date:
Related Keywords:
- Malignant Neoplasm
- Neoplasms
Name | Location |
|---|---|
| Wayne State University | Detroit, Michigan 48202 |
| M D Anderson Cancer Center | Houston, Texas 77030 |
