Cixutumumab and Temsirolimus in Treating Patients With Locally Advanced or Metastatic Cancer
Phase I Study of IMC-A12 (NSC# 742460) in Combination With Temsirolimus CCI-779 (NSC# 683864) in Patients With Advanced Cancers
7 other identifiers
interventional
72
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2008
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2008
CompletedFirst Submitted
Initial submission to the registry
May 14, 2008
CompletedFirst Posted
Study publicly available on registry
May 16, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2015
CompletedNovember 4, 2015
November 1, 2015
5.1 years
May 14, 2008
November 3, 2015
Conditions
Outcome Measures
Primary Outcomes (4)
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
Secondary Outcomes (1)
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
Study Arms (3)
Group A (temsirolimus on days 15 and 22 course 1)
EXPERIMENTALPatients 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)
EXPERIMENTALPatients 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)
EXPERIMENTALPatients receive temsirolimus IV over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22.
Interventions
Given IV
Correlative studies
Correlative studies
Given IV
Eligibility Criteria
You may qualify if:
- Patients with advanced or metastatic cancer
- Patients enrolled in the expansion cohorts may be on antidiabetic treatment, but baseline glucose should be =\< 120
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must also have signed an authorization for the release of their protected health information
- Patients are allowed to have unlimited prior treatments
- Patients must be registered in the MD Anderson Cancer Center (MDACC) institutional database (CORE) prior to treatment with study drug
- Estimated life expectancy of greater than 3 months
- Patients must be ≥ 4 weeks beyond treatment of any chemotherapy, other investigational therapy, biological, targeted agents or radiotherapy, and must have recovered to =\< grade 1 toxicity or previous baseline for each toxicity; exceptions: patients must be \>= 6 weeks beyond treatment with monoclonal antibodies; patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field
- Patients must be \>= 2 weeks beyond treatment of hormonal therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
- Absolute neutrophil count \>= 1500/mL
- Platelets \>= 100,000/mL
- Creatinine =\< 2 X upper limit of normal (ULN)
- Total (T.) bilirubin =\< 1.5 X ULN
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 X ULN
- Women of childbearing potential MUST have a negative serum or urine human chorionic gonadotropin (HCG) test unless prior hysterectomy or menopause (defined as 12 consecutive months without menstrual activity); patients should not become pregnant or breastfeed while on this study; sexually active patients must agree to use contraception prior to study entry, for the duration of study participation, and for 3 months after the last dose
- +1 more criteria
You may not qualify if:
- Patients may not be receiving any other investigational agents
- Patients who are pregnant or breastfeeding
- Patients with history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days
- Patients with uncontrolled intercurrent illness including, but not limited to, active infection requiring hospitalization
- Patients with history of hypersensitivity to monoclonal antibody treatment or immunosuppressant agents
- Patients with history of cerebrovascular accident (CVA), myocardial infarction or unstable angina within the previous six months before starting therapy
- Patients with New York Heart Association class III or greater congestive heart failure or uncontrolled hyperlipidemia (cholesterol \> 300 mg/dl; triglyceride 2.5 X ULN despite lipid lowering agent)
- Patients with fasting blood sugar \> 120; patients who are on oral hypoglycemic agents and insulin will be excluded; exception: patients in the expansion cohorts may be on antidiabetic treatment (including hypoglycemic agents and/or insulin) if controlled
- Patients on drugs that are strong P450 cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers; these drugs should be stopped 5 half-lives prior to starting investigational agents with temsirolimus; the strong inducing or inhibiting agents should not restart until 1 week after the end of study treatment; the principal investigator (PI) or his designee will go over/check the list of medication for individual patients; NOTE: Physiologic replacement of steroids (with either prednisone or hydrocortisone) in patients with adrenalectomy will be allowed
- Patients with history of brain metastasis are eligible, however the brain metastases should have been treated (treatment defined as surgery or radiation therapy \[RT\]) and the patient should have been free from symptoms/signs and off steroids for at least 3 months before study entry
- Patients with highly aggressive lymphoma (i.e. Burkitt's)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
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.
PMID: 24668327DERIVED
MeSH Terms
Conditions
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Aung Naing
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2008
First Posted
May 16, 2008
Study Start
May 1, 2008
Primary Completion
June 1, 2013
Study Completion
October 1, 2015
Last Updated
November 4, 2015
Record last verified: 2015-11