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Malignant NeoplasmPhase 1NCT00678769

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

A Phase 1 study testing Cixutumumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Malignant Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Malignant Neoplasm
What is being tested?
Cixutumumab, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
2 sitesUnited States
Study dates
May 2008to Oct 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Patients must be >= 16 years of age; patients with Ewing's Sarcoma must be >= 14 years of age

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I Study of IMC-A12 (NSC# 742460) in Combination With Temsirolimus CCI-779 (NSC# 683864) in Patients With Advanced Cancers

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Cixutumumab, Laboratory Biomarker Analysis, Pharmacological Study, Temsirolimus
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CixutumumabDrug

    Also called Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12, IMC-A12

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

Study groups in NCT00678769
Study groupRoleWhat they receive
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.
Receives: Drug: Cixutumumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus
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.
Receives: Drug: Cixutumumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus
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.
Receives: Drug: Cixutumumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline to up to day 11

  2. 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.

    Measured: Baseline to up to day 11

  3. 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

    Measured: 28 days

  4. 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.

    Measured: Baseline to up to day 28 of course 2

Secondary outcomes (1)

  1. Tumor response rate defined as CR + PR assessed by Response Evaluation Criteria in Solid Tumors and CHESON criteria

    Measured: Up to 30 days after completion of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionJun 2013
  4. Study completionOct 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00678769
Sponsor's protocol ID
NCI-2009-00282
Other IDs
NCI-2009-00282, CDR0000595388, 2007-0595, 8109, P30CA016672, U01CA062461, U01CA062487
Status last verified
Nov 2015
First submitted
14 May 2008
Last updated
4 Nov 2015
Results posted
No

Publications

  • 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.

    PubMed 24668327

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cixutumumab, Laboratory Biomarker Analysis and Pharmacological Study in people with Malignant Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in phosphorylation levels of other biomarkers before and after treatment (time frame: Baseline to up to day 11). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00678769, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2015.

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