Monoclonal Antibody IMC-A12 and Temsirolimus in Treating Patients With Locally Advanced or Metastatic Cancer - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00678223

Purpose

RATIONALE: Monoclonal antibodies, such as IMC-A12, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving monoclonal antibody IMC-A12 together with temsirolimus may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of monoclonal antibody IMC-A12 and temsirolimus in treating patients with locally advanced or metastatic cancer.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition Unspecified Adult Solid Tumor, Protocol Specific	Drug: cixutumumab Drug: temsirolimus	Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Fungal Infections Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Multiple Myeloma

Drug Information available for: Immunoglobulins Globulin, Immune CCI 779

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase I Study of IMC-A12 (NSC# 742460) in Combination With Temsirolimus CCI-779 (NSC# 683864) in Patients With Advanced Cancers

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose and dose-limiting toxicity of anti-IGF-1R recombinant monoclonal antibody IMC-A12 and temsirolimus [ Designated as safety issue: Yes ]
Change in phosphorylation levels of AKT and other biomarkers (i.e., IGF-1R, pIGF-1R, IRS-1, PTEN, VEGFR-1, VEGFR-2, and CD31) before and after treatment [ Designated as safety issue: No ]
Tumor metabolism as assessed by PET scan before and after treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tumor response rate (complete response and partial response) [ Designated as safety issue: No ]

Estimated Enrollment:	63
Study Start Date:	May 2008
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group A (MTD expansion cohort): Experimental 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 anti-IGF-1R recombinant monoclonal antibody IMC-A12 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.	Drug: cixutumumab Given IV Drug: temsirolimus Given IV
Group B (MTD expansion cohort): Experimental Patients receive anti-IGF-1R recombinant monoclonal antibody IMC-A12 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.	Drug: cixutumumab Given IV Drug: temsirolimus Given IV
Group C (MTD expansion cohort): Experimental Patients receive temsirolimus IV over 30 minutes and anti-IGF-1R recombinant monoclonal antibody IMC-A12 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.	Drug: cixutumumab Given IV Drug: temsirolimus Given IV

Detailed Description:

OBJECTIVES:

Primary

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.
To determine the maximum tolerated dose of this regimen in these patients.
To evaluate the biologic effect of this regimen on expression/phosphorylation of potential markers of response in patients with disease amenable to biopsy.
To assess tumor metabolism as assessed by PET scan.

Secondary

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 anti-IGF-1R recombinant monoclonal antibody IMC-A12 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 anti-IGF-1R recombinant monoclonal antibody IMC-A12 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 anti-IGF-1R recombinant monoclonal antibody IMC-A12 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 anti-IGF-1R recombinant monoclonal antibody IMC-A12 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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
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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00678223

Locations

United States, Texas
M. D. Anderson Cancer Center at University of Texas	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Aung Naing, MD	M.D. Anderson Cancer Center
Investigator:	Patricia M. LoRusso, DO	Barbara Ann Karmanos Cancer Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000595388, MDA-2007-0595
Study First Received:	May 9, 2008
Last Updated:	December 17, 2008
ClinicalTrials.gov Identifier:	NCT00678223
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
accelerated phase chronic myelogenous leukemia
acute undifferentiated leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
mast cell leukemia
meningeal chronic myelogenous leukemia
progressive hairy cell leukemia, initial treatment

prolymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage III adult T-cell leukemia/lymphoma
stage III chronic lymphocytic leukemia
stage IV adult T-cell leukemia/lymphoma
stage IV chronic lymphocytic leukemia
T-cell large granular lymphocyte leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia

Study placed in the following topic categories:

Blast Crisis
Sezary syndrome
Chronic myelogenous leukemia
Hodgkin lymphoma, adult
Lymphoma, small cleaved-cell, diffuse
Lymphoma, large-cell, immunoblastic
Lymphomatoid granulomatosis
Preleukemia
Leukemia, Prolymphocytic
Hemorrhagic Disorders
Hemorrhagic thrombocythemia
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic
Immunoglobulins

Myelodysplastic syndromes
Essential thrombocytosis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Myelodysplastic myeloproliferative disease
Waldenstrom Macroglobulinemia
Plasmacytoma
Leukemia, Myeloid, Accelerated Phase
B-cell lymphomas
Anaplastic large cell lymphoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Disease

Immune System Diseases
Syndrome
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 15, 2009