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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

Phase 1
18 Years
Open (Enrolling)
Male Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


I. To determine the maximally tolerated dose (MTD) of cilengitide and paclitaxel at weekly
dose schedule.

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.

V. To evaluate the effect of cilengitide and paclitaxel on circulating Cyr61 using a novel
"sandwich ELISA" assay and to correlate this effect with clinical response.

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.

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.

Inclusion Criteria:

- Histologic proof of cancer that is now unresectable (solid tumors, excluding

- For Cohort II only: breast cancer patients who have progressed on taxanes are
eligible ("progression on taxanes" is defined as any type of prior taxane exposure,
that is, patients that progress during taxane treatment, immediately after taxane

- ANC ≥ 1500/μL

- Hgb ≥ 9 g/dL

- PLT ≥ 100,000/μL

- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

- AST ≤ 3 x ULN or AST ≤ 5 x ULN if liver involvement

- Creatinine ≤ 1.5 x ULN

- ECOG performance status (PS) 0, or 1 (or KPS > 70)

- Ability to provide informed consent

- Willingness to return to the enrolling Mayo Clinic institution for follow-up

- Life expectancy ≥ 12 weeks

- Willingness to provide blood samples for the mandatory correlative research component

- For Cohort II, available tissue is mandatory (tissue has to be enough to allow
testing for the proposed biomarkers; otherwise, a biopsy to obtain new tissue is

- 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 postmenopause

- Patients on hormonal therapy for breast cancer are allowed to continue their hormonal

Exclusion Criteria:

- 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

- 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

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- New York Heart Association classification III or IV

- 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

- NOTE: This study involves an investigational agent whose genotoxic, mutagenic
and teratogenic effects on the developing fetus and newborn are unknown

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-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 HIV positive on HAART therapy as there is a risk for
drug interaction with antiretroviral treatment

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number and severity of all adverse events (overall, by dose-level, and by tumor group), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Outcome Description:

Tabulated and summarized in this patient population.

Outcome Time Frame:

Up to 3 months

Safety Issue:


Principal Investigator

Julian Molina

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

Related Keywords:

  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Breast Neoplasms
  • Breast Neoplasms, Male



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Mayo Clinic in FloridaJacksonville, Florida  32224