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Adult Solid NeoplasmPhase 1NCT01548482

Trebananib And Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temsirolimus in people with Adult Solid Neoplasm and Lung Carcinoid Tumor, run by National Cancer Institute (NCI) at 3 sites in Canada.

Completed

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

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and the best dose of trebananib and temsirolimus when given together in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
3 sitesCanada
Study dates
Mar 2012to Jan 2014
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • DOSE ESCALATION COHORTS: Patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • DOSE EXPANSION COHORTS: Patients must have histologically and/or cytologically confirmed uterine cancer, renal cell cancer or carcinoid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • DOSE ESCALATION COHORTS: No limitation on prior therapy; however, there must be at least a 4 week interval between initiation of study treatment and any prior radiotherapy or systemic therapy, 6 weeks if the last regimen included carmustine (BCNU) or mitomycin C; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy for symptomatic palliation; please contact the study coordinator at the Princess Margaret Hospital (PMH) Phase I Consortium Central Office or the principal investigator if any questions arise about interpretation of this criterion
  • EXPANSION COHORTS:
  • Uterine cancer: Patients diagnosed with uterine cancer will be eligible provided they have received at least one prior line of chemotherapy for recurrent or metastatic disease unless the investigator feels that cytotoxic chemotherapy is contraindicated; prior hormonal treatment will be allowed; prior anti-angiogenic agents and prior treatment with agents targeting phosphatidylinositol 3-kinase (PI3K)- protein kinase B (AkT)- mammalian target of rapamycin (mTOR) pathway are not allowed
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  • Renal cell cancer: Patients diagnosed with renal cell cancer (RCC) will be required to have received at least one prior line anti- vascular endothelial growth factor (VEGF)/ receptor (R) treatment (i.e. bevacizumab, sunitinib, and/or sorafenib); prior treatment with agents targeting PI3K-Akt-mTOR pathway is not allowed
  • Carcinoid tumor: Patients diagnosed with carcinoid tumor must have demonstrated radiographic evidence of disease progression within six months prior to enrollment; prior and/or concurrent long-acting somatostatin analogue therapy is allowed; if patient is continued on a long-acting somatostatin analogue, a stable dose for >= 2 months prior to study entry is required with documentation of progressive disease on current dose; prior radiolabeled octreotide therapy is allowed; prior regional treatments for liver metastasis are permitted including:
  • Selective internal radiation therapy (i.e. brachytherapy, radiolabeled microsphere embolization, etc)
  • Hepatic artery chemoembolization
  • Hepatic artery embolization
  • Hepatic artery infusional chemotherapy
  • Radiofrequency ablation
  • Patients must be > 12 weeks from regional treatments and show progressive disease in the liver after regional therapy or must have measurable disease outside the liver; patients may have received one prior line of anti-VEGF/R treatment (e.g. bevacizumab, sunitinib, and/or sorafenib); prior treatment with agents targeting PI3K-Akt-mTOR pathway is not allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3.0 x 10^9/L
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 90 g/L (or >= 9 g/dL)
  • Total bilirubin =< institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal if no known liver metastasis or =< 5 x institutional upper limit of normal if known liver metastasis
  • Partial thromboplastin time (PTT) or activated PTT (aPTT) =< 1.5 x ULN per institutional laboratory range and international normalized ratio (INR) =< 1.5
  • Creatinine =< institutional ULN OR creatinine clearance > 40 mL/min per 24 hours (h) urine collection or calculated according to the Cockcroft-Gault formula
  • Urinary protein =< 30 mg/dL in urinalysis or =< 1 + on dipstick, unless quantitative protein is < 1000 mg in a 24 h urine sample
  • Total cholesterol < 400 mg/dL (or < 10.34 mmol/L)
  • Serum triglyceride level < 500 mg/dL (or < 5.7 mmol/L)
  • Generally well-controlled blood pressure with systolic blood pressure =< 140 mm Hg AND diastolic blood pressure =< 90 mm Hg prior to enrollment; the use of anti-hypertensive medications to control hypertension is permitted
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 6 months after completion of AMG386 and/or temsirolimus administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of AMG386 and/or temsirolimus administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • History of central nervous system metastases
  • History of venous or arterial thromboembolism within 12 months prior to enrollment/randomization; patients requiring ongoing anticoagulation with therapeutic dosages of low molecular weight heparin or warfarin are excluded
  • History of clinically significant bleeding within 6 months of enrollment/randomization
  • Unresolved toxicities from prior systemic therapy that are Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 >= grade 2 in severity except alopecia
  • Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or TEK tyrosine kinase, endothelial (Tie2) receptor
  • Clinically significant cardiovascular disease within 12 months prior to enrollment/randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent
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  • Major surgery within 28 days prior to enrollment or still recovering from prior surgery
  • Minor surgical procedures, except placement of tunneled central venous access device within 3 days (7 days if with VEGF inhibitor) prior to randomization/enrollment
  • Treatment within 30 days prior to enrollment with strong immune modulators, including but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept, anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab
  • Non-healing wound, ulcer (including gastrointestinal), or fracture
  • Subject not consenting to the use of highly effective contraceptive precautions (e.g., double barrier method [i.e., condom plus diaphragm]) during the course of the study and for 6 months after administration of the last study medication
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AMG 386 or temsirolimus
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who have not yet completed at least 21 days (30 days for prior monoclonal antibody therapy) since ending other investigational device or drug trials, or who are currently receiving other investigational treatments
  • Temsirolimus is a cytochrome P450 3A4 (CYP3A4) substrate; patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with AMG 386; these potential risks may also apply to temsirolimus
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients with pre-existing clinically significant pulmonary infiltrates of unknown origin
  • Patients with an indwelling peritoneal or pleural catheter that is used to manage malignant effusions
  • Known intra-abdominal inflammatory process or serious gastrointestinal ulceration
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No gastric or esophageal varices
  • Patients with primary bowel tumors in situ or recurrent disease at bowel anastomosis

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: A Phase I Trial of AMG 386 and Temsirolimus in Advanced Solid Tumors With an Expansion Cohort in Uterine Cancer, Renal Cell Carcinoma and Carcinoid Tumor

This phase I trial studies the side effects and the best dose of trebananib and temsirolimus when given together in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving trebananib with temsirolimus may be an effective treatment for solid tumors.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase II dose (RP2D) and safety profile of AMG 386 (trebananib) in combination with temsirolimus in patients with advanced solid tumors.

SECONDARY OBJECTIVES:

  1. To evaluate pharmacodynamic (PD) effects of both drugs when administered in combination, with the goal of identifying potential predictive and PD markers that need further exploration and validation in future trials.

II. To explore preliminary anti-tumor activity of both drugs when administered at the RP2D to patients with advanced endometrial cancer, renal cell carcinoma, or carcinoid tumor.

OUTLINE: This is a dose-escalation study of trebananib.

Patients receive trebananib intravenously (IV) over 60 minutes and temsirolimus IV over 30-60 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 for 30 days.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Temsirolimus, Trebananib
Medical subject headings
Carcinoma, Renal Cell

What participants receive

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

  • 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

  • TrebananibBiological

    Also called AMG 386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

    Given IV

Study groups in NCT01548482
Study groupRoleWhat they receive
Treatment (trebananib, temsirolimus)ExperimentalPatients receive trebananib IV over 60 minutes and temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Temsirolimus; Biological: Trebananib

What is being measured

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

  1. RP2D of trebananib and temsirolimus defined as the dose level at which =< 1/6 patients experienced dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) CTCAE version 4.0

    Measured: 28 days

  2. Safety profile of trebananib and temsirolimus as assessed by NCI CTCAE version 4.0

    Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occurring, serious and severe events of interest. Adverse events will be summarized using all adverse events experienced, although a subanalysis may be conducted including only those adverse events in which the treating physician deems possibly, probably or definitely attributable to one or both study treatments.

    Measured: Up to 30 days

Secondary outcomes (2)

  1. Objective response to treatment assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1

    Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate.

    Measured: Up to 30 days

  2. PD effects of both drugs when administered in combination

    Standard descriptive statistics, such as the mean, median, range and proportion, will be used to summarize the patient sample and to estimate parameters of interest. Ninety-five percent confidence intervals will be provided for estimates of interest where possible.

    Measured: Course 1 days 1, 3, and 8 and course 2 day 1

Timeline

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

  1. First posted8 Mar 2012 (estimated)
  2. Study startMar 2012
  3. Primary completionJan 2014
  4. Study completionJan 2014

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01548482
Sponsor's protocol ID
NCI-2012-02848
Other IDs
NCI-2012-02848, CDR0000728823, PJC-008, 9041, U01CA132123, UM1CA186644
Status last verified
May 2015
First submitted
24 Feb 2012
Last updated
6 Oct 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Laboratory Biomarker Analysis, Pharmacological Study and Temsirolimus in people with Adult Solid Neoplasm and Lung Carcinoid Tumor, run by National Cancer Institute (NCI) at 3 sites in Canada.

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 30 inclusion and 24 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 6 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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?

RP2D of trebananib and temsirolimus defined as the dose level at which =< 1/6 patients experienced dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) CTCAE version 4.0 (time frame: 28 days). The study lists 2 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 NCT01548482.

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 6 Oct 2015.

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