AzTrials
AzTrials

Adult Solid NeoplasmPhase 1NCT01276496

Weekly Doses of Cilengitide and Paclitaxel in Treating Patients With Advanced Solid Tumors That Cannot Be Removed by Surgery

A Phase 1 study testing Cilengitide, Laboratory Biomarker Analysis and Paclitaxel in people with Adult Solid Neoplasm and Estrogen Receptor Negative, run by National Cancer Institute (NCI) at 3 sites in United States.

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 cilengitide when given together with paclitaxel weekly in treating patients with solid tumors that have spread nearby or to other areas of the body and cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cilengitide, Laboratory Biomarker Analysis and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
3 sitesUnited States
Study dates
Dec 2010to Mar 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
  • For Cohort II only:
  • Histologic adenocarcinoma of the breast with manifestations of metastatic cancer or locally advanced, unresectable cancer
  • Estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptor negative disease per local standards
  • Refractory to taxanes which is defined as one of the following:
  • Having relapsed during or within 12 months of completing adjuvant paclitaxel or docetaxel
Show all 23Show fewer
  • Disease progression while on any taxane in the locally advanced, unresectable or metastatic breast cancer setting
  • Ability and willingness to undergo biopsy for biomarker testing prior to start of treatment
  • Disease must be measurable by imaging-based evaluation per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (v1.1)
  • Up to 5 prior regimens of chemotherapy for metastatic disease are allowed
  • Absolute neutrophil count (ANC) >= 1500/μL
  • Hemoglobin (Hgb) >= 9 g/dL
  • Platelets (PLT) >= 100,000/μL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) =< 3 x ULN or AST =< 5 x ULN if liver involvement
  • Creatinine =< 1.5 x ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, or 1 (or Karnofsky performance status [KPS] > 70)
  • Ability to provide informed consent
  • Willingness to return to the enrolling Mayo Clinic institution for follow-up
  • Life expectancy >= 12 weeks
  • All patients: Willingness to provide blood samples for the mandatory correlative research component
  • For Cohort II, tissue biopsies are mandatory
  • Women of childbearing potential only: negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential including women within 2 years of post-menopause

Who cannot join

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • 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
  • Any of the following prior therapies:
  • Chemotherapy =< 21 days prior to registration
  • Mitomycin C/nitrosoureas =< 42 days prior to registration
  • Immunotherapy =< 14 days prior to registration
Show all 28Show fewer
  • Biologic therapy =< 14 days prior to registration
  • Prior investigational therapy =< 28 days prior to registration
  • Full field radiation therapy =< 28 days prior to registration or limited field radiation therapy < 14 days prior to registration
  • Full field radiation encompasses the entire area of known disease involvement and surrounding uninvolved but at-risk areas, e.g. subtotal nodal (mantle and upper abdomen) or total nodal irradiation
  • Limited field radiation is restricted to treating only the known areas of clinical disease, e.g. involved-field therapy for lymphoma
  • Major surgery (i.e., laparotomy) =< 4 weeks prior to registration; minor surgery =< 2 weeks prior to registration; Note: insertion of a vascular access device is not considered major or minor surgery in this regard
  • Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to =< grade 1, unless the patient has a chronic, stable =< grade 2 toxicity that would not interfere with the evaluation of the study agents
  • New York Heart Association classification III or IV
  • Central nervous system (CNS) metastases or seizure disorder; Note: CNS metastases are allowed if previously treated and stable for at least 4 weeks
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, injections, intrauterine device [IUD], or abstinence, etc.); oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive on highly active antiretroviral therapy (HAART) therapy
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 3 years prior to registration; EXCEPTIONS: nonmelanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
  • History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • Uncontrolled hypertension, labile hypertension of history of poor compliance with antihypertensive medication
  • Patients with active, bleeding diathesis
  • Non-disease related- major surgery, =< 28 days or minor surgery =< 7 days prior to registration

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: A Phase I, Open Label, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetic Properties of the Combination of Cilengitide and Paclitaxel in Patients With Advanced Solid Malignancies

This phase I trial studies the side effects and the best dose of cilengitide when given together with paclitaxel weekly in treating patients with solid tumors that have spread nearby or to other areas of the body and cannot be removed by surgery. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, work in different ways to the stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cilengitide together with paclitaxel may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximally tolerated dose (MTD) of cilengitide and paclitaxel at weekly dose schedule. (Cohort I) II. To describe the toxicities associated with cilengitide and paclitaxel. III. To describe any antitumor activity of cilengitide and paclitaxel at weekly dose schedule.

IV. To characterize pharmacokinetics (PK) of cilengitide and paclitaxel with the proposed schedule and correlate PK parameters to clinical outcome. (Cohort I) V. To examine the effect of cilengitide and paclitaxel on circulating cysteine-rich, angiogenic inducer, 61 (Cyr61) using a novel "sandwich enzyme-linked immunosorbent assay (ELISA)" and to correlate this effect with clinical response. (Cohort II) VI. To evaluate the information obtained through use of items from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Phase I studies.

VII. To determine if tumor tissue expression of alpha v beta 3 (αvβ3) and CYR61 correlate with therapeutic response to cilengitide with paclitaxel. (Cohort II)

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

Patients receive cilengitide intravenously (IV) over 1 hour on days* 1, 8, and 15 and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Some patients receive cilengitide IV over 1 hour on days 1, 2, 8, 9, 15, and 16.

After completion of study treatment, patients are followed up for 3 months.

Being tested
Cilengitide, Laboratory Biomarker Analysis, Paclitaxel, Pharmacological Study
Medical subject headings
Breast Neoplasms, Male, Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

  • CilengitideDrug

    Also called EMD 121974, EMD-121974

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01276496
Study groupRoleWhat they receive
Treatment (cilengitide, paclitaxel)ExperimentalPatients receive cilengitide IV over 1 hour on days* 1, 8, and 15 and paclitaxel IV over 1 hour on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: *Some patients receive cilengitide IV over 1 hour on days 1, 2, 8, 9, 15, and 16.
Receives: Drug: Cilengitide; Other: Laboratory Biomarker Analysis; Drug: Paclitaxel; Other: Pharmacological Study

What is being measured

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

  1. Best response, defined to be complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group).

    Measured: From start of the treatment until disease progression/recurrence, assessed up to 3 months

  2. Change in Cyr61 expression levels (Cohort II)

    At the end of each cycle, the percent change in serum Cyr61 expression from pre-treatment levels will be determined for each patient. For each patient, a times series plot of the percent change in serum Cyr61 expression from pre-treatment levels will be constructed and visually inspected for trends across time as well as for differences between those who respond to treatment (CR or PR by RECIST criteria) and those who do not.

    Measured: Baseline to up to 3 months

  3. Change in Cyr61 expression levels (Cohort II)

    A Wilcoxon rank sum test will be used to assess the percent change in Cyr61expression level after one cycle of treatment from pretreatment levels differs between those who progress within 120 days (within the first 6 cycles of treatment) and those who remain progression-free at least 120 days.

    Measured: Baseline to 21 days

  4. Incidence of grade 3+ adverse events, as graded using NCI CTCAE v 4.0

    The number and severity of grade 3+ adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

    Measured: Up to 3 months

  5. Incidence of hematologic toxicity, including thrombocytopenia, neutropenia, and leukopenia, evaluated via the ordinal CTC

    Assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 3 months

  6. Incidence of non-hematologic toxicity, evaluated via the ordinal Common Toxicity Criteria (CTC)

    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 3 months

  7. MTD of cilengitide and paclitaxel, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients as graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0

    Measured: 3 weeks

  8. Number of all adverse events, graded according to the NCI CTCAE v4.0

    The number of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

    Measured: Up to 3 months

  9. Overall survival (OS) (Cohort II)

    Kaplan-Meier method will be used to estimate the distribution of OS time.

    Measured: The time of registration to death due to any cause, assessed up to 3 months

  10. Progression-free survival (PFS) (Cohort II)

    Kaplan-Meier method will be used to estimate the distribution of PFS time.

    Measured: The time of registration to documentation of disease event where a disease event is local/regional/distant progression, contralateral breast disease, second primary disease or death due to any cause, assessed up to 3 months

  11. Response rate, defined as the proportion of patients whose tumor responds to treatment (Cohort II)

    Calculated as the number of eligible patients whose tumor meets the criteria for a CR or PR on two consecutive evaluations at least 6 weeks apart divided by the number of eligible patients with metastatic breast cancer refractory to taxanes who begin treatment. A 95% binomial confidence interval will be constructed for the true response rate.

    Measured: Up to 3 months

  12. Severity of all adverse events, graded according to NCI CTCAE v4.0

    The severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population.

    Measured: Up to 3 months

  13. Time to progression

    Measured: Up to 3 months

  14. Time to treatment failure

    Measured: Time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months

  15. Time until any treatment related toxicity

    Measured: Up to 3 months

  16. Time until hematologic nadir for ANC

    Measured: Up to 3 months

  17. Time until hematologic nadir for platelets

    Measured: Up to 3 months

  18. Time until hematologic nadir for WBC

    Measured: Up to 3 months

  19. Time until treatment related grade 3+ toxicity

    Measured: Up to 3 months

Secondary outcomes (1)
  1. Incidence of toxicity, as assessed using PRO-CTCAE

    The PRO-CTCAE will be summarized descriptively, and the dropout rate will be used for feasibility study. Informal comparison and correlation of the PRO-CTCAE symptoms with their corresponding items in clinician reported CTCAE will be conducted in an exploratory manner. Chi-squared tests will be used without adjustment for multiple comparisons.

    Measured: Up to 3 months

Timeline

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

  1. First posted13 Jan 2011 (estimated)
  2. Study startDec 2010
  3. Primary completionMar 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01276496
Sponsor's protocol ID
NCI-2013-00619
Other IDs
NCI-2013-00619, U01CA069912, MC0915, 8335, P30CA015083
Status last verified
Mar 2015
First submitted
12 Jan 2011
Last updated
15 Mar 2016
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cilengitide, Laboratory Biomarker Analysis and Paclitaxel in people with Adult Solid Neoplasm and Estrogen Receptor Negative, run by National Cancer Institute (NCI) at 3 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 23 inclusion and 28 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 15 Mar 2016. 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 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?

Best response, defined to be complete response (CR) or partial response (PR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (time frame: From start of the treatment until disease progression/recurrence, assessed up to 3 months). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 15 Mar 2016.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in