| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2009-00282 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000595388 | |||
| 2007-0595 | Other Identifier | M D Anderson Cancer Center | |
| 8109 | Other Identifier | CTEP | |
| P30CA016672 | U.S. NIH Grant/Contract | View source | |
| U01CA062461 | U.S. NIH Grant/Contract | View source | |
| U01CA062487 | U.S. NIH Grant/Contract | View source |
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This phase I trial studies the side effects and best dose of cixutumumab and temsirolimus in treating patients with locally advanced or metastatic cancer. Monoclonal antibodies, such as cixutumumab, 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 cixutumumab together with temsirolimus may kill more cancer cells.
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability; and to determine maximum tolerated dose (MTD) of the combination of IMC-A12 (cixutumumab) with temsirolimus in patients with or without biopsiable advanced cancers.
II. To evaluate the biologic effect of each individual drug and this drug combination on expression/phosphorylation of potential markers of response in patients with biopsiable disease.
III. To assess tumor metabolism by positron emission tomography (PET).
SECONDARY OBJECTIVES:
I. To report the clinical tumor response of this combination in a descriptive fashion.
OUTLINE:
DOSE ESCALATION PHASE: Patients receive temsirolimus intravenously (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 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.
After completion of study treatment, patients are followed up within 30 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A (temsirolimus on days 15 and 22 course 1) | 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 cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. |
|
| Group B (cixutumumab on days 15 and 22 of course 1) | Experimental | 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. |
|
| Group C (temsirolimus on days 1, 8, 15, and 22) | Experimental | Patients receive temsirolimus IV over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cixutumumab | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in phosphorylation levels of other biomarkers before and after treatment | Other markers include: insulin-like growth factor 1 receptor (IGF-1R), phosphorylated (p)IGF-1R, insulin receptor substrate-1 (IRS-1), phosphatase and tensin homolog gene (PTEN), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and cluster of differentiation (CD)31. Generalized Estimating Equations model will be used to model the correlated IHC score between treatment arms. | Baseline to up to day 11 |
| Change in phosphorylation levels of v-akt murine thymoma viral oncogene homolog 1 in terms of difference in IHC score | Generalized Estimating Equations model will be used to model the correlated IHC score between treatment arms. | Baseline to up to day 11 |
| 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 toxicity | 28 days | |
| Tumor metabolism as assessed by PET scan before and after treatment | The PET standardized uptake value (SUV) of all patients will be pooled together to plot the overall trend of PET SUV over time, the percent change in PET SUV will be estimated and 95% confidence intervals will be provided. | Baseline to up to day 28 of course 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor response rate defined as CR + PR assessed by Response Evaluation Criteria in Solid Tumors and CHESON criteria | Up to 30 days after completion of study treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Aung Naing | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States | ||
| M D Anderson Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24668327 | Derived | Liu X, Lorusso P, Mita M, Piha-Paul S, Hong DS, Fu S, McQuinn L, Asatiani E, Doyle LA, Chen HX, Hess KR, Kurzrock R, Naing A. Incidence of mucositis in patients treated with temsirolimus-based regimens and correlation to treatment response. Oncologist. 2014 Apr;19(4):426-8. doi: 10.1634/theoncologist.2013-0231. Epub 2014 Mar 25. |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C557414 | cixutumumab |
| C401859 | temsirolimus |
| D020123 | Sirolimus |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Pharmacological Study | Other | Correlative studies |
|
| Temsirolimus | Drug | Given IV |
|
|
| Houston |
| Texas |
| 77030 |
| United States |