Cilengitide and Paclitaxel in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery

• Register: ClinicalTrials.gov
• Last refreshed on: 14 January 2013
• Main ID: NCT01276496
• Date of registration: 12/01/2011
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Cilengitide and Paclitaxel in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery
• Scientific 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
• Date of first enrolment: December 2010
• Target sample size: 32
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01276496
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Julian Molina
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Inclusion Criteria:

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

- 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
treatment)

- Absolute neutrophil count (ANC) >= 1500/uL

- Hemoglobin (Hgb) >= 9 g/dL

- Platelet (PLT) >= 100,000/uL

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

- 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
therapy

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

- 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; NOTE: *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

- Central nervous system (CNS) metastases or seizure disorder; Note: CNS metastases are
allowed if previously treated and stable for at least 4 weeks

- 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-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 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: Non-melanotic
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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Male Breast Cancer

Recurrent Breast Cancer

Stage IIIB Breast Cancer

Stage IV Breast Cancer

Unspecified Adult Solid Tumor, Protocol Specific

Intervention(s)

Drug: cilengitide

Drug: paclitaxel

Other: enzyme-linked immunosorbent assay

Other: laboratory biomarker analysis

Other: pharmacological study

Primary Outcome(s)

Antitumor activity of cilengitide and paclitaxel at weekly dose schedule [Time Frame: Baseline and every 2 courses]

Effect of cilengitide and paclitaxel on circulating Cyr61 using a novel "sandwich ELISA" assay and correlation of this effect with clinical response [Time Frame: Baseline and prior to each courses in MTD cohort]

MTD of cilengitide and paclitaxel at weekly dose schedule [Time Frame: 3 weeks]

PK of cilengitide and paclitaxel with the proposed schedule and correlation of PK parameters to clinical outcome [Time Frame: Days 1-5 and 15 of courses 1 and 2]

Toxicities associated with cilengitide and paclitaxel [Time Frame: Baseline and prior to each course]

Secondary Outcome(s)

Evaluation of information obtained through use of items from the PRO-CTCAE in Phase I studies [Time Frame: Baseline and weekly during course 1 for dose-escalation cohort; baseline and weekly during courses 1-2 for MTD cohort]

Secondary ID(s)

CDR0000692190

MC0915

NCI-2011-00024

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Mayo Clinic