Cixutumumab and Temsirolimus in Treating Patients With Locally Advanced or Metastatic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00678769
First received: May 14, 2008
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

This phase I trial is studying 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.


Condition Intervention Phase
Malignant Neoplasm
Drug: cixutumumab
Drug: temsirolimus
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of IMC-A12 (NSC# 742460) in Combination With Temsirolimus CCI-779 (NSC# 683864) in Patients With Advanced Cancers

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 [ Time Frame: 28 days ] [ 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 [ Time Frame: Baseline and up to 30 days ] [ Designated as safety issue: No ]
  • Tumor metabolism as assessed by PET scan before and after treatment [ Time Frame: Baseline and up to 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response rate defined as complete response (CR) + partial response (PR) assessed by RECIST and CHESON [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: May 2008
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
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.
Drug: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: II
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.
Drug: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Experimental: III
Patients receive temsirolimus IV over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22.
Drug: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00678769

Locations
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Aung Naing M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00678769     History of Changes
Obsolete Identifiers: NCT00678223
Other Study ID Numbers: NCI-2009-00282, NCI-2009-00282, CDR0000595388, 2007-0595, 8109, U01CA062461, P30CA016672, U01CA062487
Study First Received: May 14, 2008
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Antibodies, Monoclonal
Sirolimus
Everolimus
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 14, 2014