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A Phase 2 Study of EMD 121974 (Cilengitide, NSC 707544) in Patients With Metastatic Melanoma

Phase 2
18 Years
Not Enrolling
Stage III Melanoma, Stage IV Melanoma

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Trial Information

A Phase 2 Study of EMD 121974 (Cilengitide, NSC 707544) in Patients With Metastatic Melanoma


I. To evaluate the clinical efficacy of EMD 121974 at two different doses in patients with
metastatic melanoma by determining the progression-free survival rate at 8 weeks.


I. To determine the response rate of EMD 121974 in patients with metastatic melanoma.

II. To determine the overall survival in patients who receive EMD 121974. III. To determine
the safety and toxicity of EMD 121974 in patients with metastatic melanoma.

IV. To determine the population pharmacokinetics of EMD 121974. V. To determine the
biological activity of EMD 121974 in melanoma cells of patients who are treated with the

VI. To evaluate the use of optical imaging and functional dynamic imaging scans in assessing
biological activity of EMD 121974.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to
prior systemic treatment (yes vs no), visceral metastases (yes vs no), serum lactic
dehydrogenase level (normal vs abnormal), and tumor integrin α_vβ_3 overexpression (yes vs
no). Patients are randomized into 1 of 2 treatment arms.

ARM I: Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11*, 15, 18, 22, and 25.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *For the first course only, treatment is omitted on day 11.

ARM II: Patients receive cilengitide as in arm I at a higher dose.

After completion of study treatment, patients are followed every 3 months for 1 year and
then every 6 months thereafter.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed stage IV or unresectable
stage III metastatic melanoma of cutaneous, mucosal or unknown origin

- 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) as >=
15 mm with conventional techniques or with spiral CT scan; in case of obviously
visible cutaneous metastatic lesions, the margins of the lesions should be clearly
defined and measured in at least one dimension as >= 10 mm

- Patient may have received prior interferon therapy (only in an adjuvant setting for
resected stage III melanoma) and/or up to 1 prior systemic treatment regimen
(chemotherapy, biotherapy, or biochemotherapy) for stage IV disease; active vaccine
therapy will not be considered as "prior systemic treatment"

- Radiographic studies used to assess disease must have been performed within 21 days
prior to registration; if a target lesion has been previously embolized, perfused or
irradiated, there must be objective evidence of progression before start of therapy
to be considered for response assessment

- ECOG performance status ≤ 2 (or Karnofsky ≥ 60%)

- Leukocytes >= 3,000/microL

- Absolute neutrophil count >= 1,500/microL

- Platelets >= 100,000/microL

- Total bilirubin =< 1.5 X institutional upper limit of normal

- ALT(SGPT) =< 2.5 X institutional upper limit of normal

- Creatinine =< 1.5 X institutional upper limit of normal

- Patient must have a hemoglobin >= 9 gm/dL (this may be achieved by transfusion if
needed) obtained within 14 days prior to registration; in case that PRBC transfusion
is needed to obtain a hemoglobin level of >= 9 gm/dL, the hemoglobin level should not
be reduced more than 1 gm/dL for at least 1 week

- The effects of EMD 121974 on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason and because antiangiogenic agents are
known to be teratogenic, 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; should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients with metastatic melanoma of choroidal origin

- Patients must not have received the following drugs prior to enrollment: endostatin,
angiostatin, bevacizumab or any integrin-targeted drugs

- Subjects who require concurrent treatment with a non-permitted medication (such as
anticoagulant therapy other than for flushing of intravenous port device, or used for
thrombosis prophylaxis)

- 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 to grade 1 toxicity from adverse events due to agents administered more
than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events; however, the following is the exception; patients who have no radiographical
evidence of recurrences in the brain for at least 3 months after the complete
resection of the brain metastases or who have asymptomatic brain metastases stable
for at least 3 months since the whole brain radiation therapy and/or stereotactic
radiosurgery will be eligible for this study; patients must not require a steroid
treatment for brain metastases

- Subjects with a history of wound-healing disorders, advanced coronary disease (such
as unstable angina pectoris or arrhythmia LOWN IV [defined as 2 or more consecutive
ventricular premature complexes], cardiac or cardiovascular abnormalities NYHA
III/IV), or with a recent history (within 6 months) of peptic ulcer disease

- 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 because EMD 121974 is an antiangiogenic
agent with the potential for teratogenic or abortifacient effects; because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with EMD 121974, breastfeeding should be discontinued if the
mother is treated with EMD 121974; lactating women must not breastfeed

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease-free for 5 years

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

Each dose of EMD 121974 will be analyzed separately.

Outcome Time Frame:

At 8 weeks

Safety Issue:


Principal Investigator

Kevin Kim

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2004

Completion Date:

Related Keywords:

  • Stage III Melanoma
  • Stage IV Melanoma
  • Melanoma



M D Anderson Cancer Center Houston, Texas  77030