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A Phase I, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Advanced Malignant Solid Tumors

Phase 1
18 Years
Not Enrolling
Solid Tumors

Thank you

Trial Information

A Phase I, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of Genz-644282 in Patients With Advanced Malignant Solid Tumors

This is a Phase I, open-label, multicenter, dose-escalation study designed to assess the
safety and tolerability of Genz-644282, administered as an IV infusion, to patients with
advanced malignant solid tumors. Drug will be administered as a 60-minute IV infusion on
days 1, 8, and 15 of the 28 day treatment cycle, or on days 1 and 8 of the 21 day treatment

Treatment with Genz-644282 will continue until disease progression or unacceptable toxicity
is observed. Patients will be enrolled in escalating dose cohorts until the Maximum
Tolerated Doses (MTDs) are established.

Safety will be evaluated throughout the study.

Inclusion Criteria:

- Signed written informed consent

- Patients enrolled in dose-escalation phase: Histologically or cytologically confirmed
advanced malignant solid tumor for which no standard therapeutic option exists.

- For the disease indications evaluated in the expansion phase, the following criteria
must be met:

1. Have one of the following histologically or cytologically confirmed advanced
malignant solid tumors for which no standard therapeutic option exists:

- Colorectal cancer (prior systemic regimen must have included ≥1 of the
following: fluoropyrimidine or oxaliplatin);

- Squamous Non-small cell lung cancer or small cell lung cancer (prior
systemic regimen must have included ≥1 of the following: cis-platinum or
carbo platinum);

- Pancreatic cancer (prior systemic regimen must have included gemcitabine);

- Breast cancer (prior systemic regimen must have included ≥1 of the
following: taxane, anthracycline, or fluoropyrimidine)

2. Received no more than 4 prior systemic therapy regimens for their malignancy

3. Experienced progression or intolerance to their immediate prior systemic therapy

- Evaluable or measurable disease.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Life expectancy of at least 12 weeks.

- Adequate organ and hematologic function.

- Prior chemotherapy, major surgery, or irradiation must have been completed at least 3
weeks prior to starting treatment with study drug, with the exception of mitomycin-C
or nitrosoureas, which should be completed at least 6 weeks prior. Additionally,
patients must have recovered to ≤ Grade 1 toxicities incurred as a result of the
previous therapy, with the exception of nail dystrophy, alopecia, or local radiation
therapy induced adverse events (e.g., impotence or incontinence). A patient who has
received radiation to < 5% of their total bone marrow volume and who has had 2 weeks
of rest may be considered for study entry after discussion with the Sponsor

- Hormone treatment must have been completed > 2 weeks prior to receiving study drug.

- Prostate cancer patients who are chemically castrated with hormonal therapy (e.g.,
luteinizing hormone-releasing hormone agonists) will be allowed to enter the study.
However, doses and schedules of such treatments must be maintained throughout the
trial and all major toxicities must have resolved to ≤ Grade 1 prior to study entry.

- Concomitant stable treatment with bisphosphonates is allowed, unless dose requires
readjustments or discontinuation.

- Ability to comply with study procedures and follow-up examinations.

- Male and female patients must agree to use an effective barrier means of birth
control (i.e., latex condom, diaphragm, cervical cap, etc.) throughout the entire
duration of the study and for at least 3 months after last dose of study drug.

- Male patients must agree to not donate sperm throughout the study and for at least 3
months following the last dose of study drug.

Exclusion Criteria:

- Received previous treatment with or have a known hypersensitivity to Genz-644282 or
to any of its components.

- Received radiotherapy to the only site of measurable disease, unless the tumor at
this site continues to increase in size after the patient has completed radiotherapy

- Used any investigational agent, other than anti-cancer chemotherapy, during the 4
weeks prior to the first dose of Genz-644282.

- Have psychiatric disorder(s) that would interfere with consent, study participation,
or follow up (with the possible exception of incompetence as defined by New Jersey
for the purposes of participation in clinical trials in the state of New Jersey).

- Have uncontrolled congestive heart failure or angina, a history of myocardial
infarction within 6 months prior to study enrollment, or a cardiac functional
capacity Class III or IV, as defined by the New York Heart Association

- Have a resting QT with Bazett's correction (QTcB) interval of > 460 msec, calculated
as the average of at least 2 of the longest QT intervals measured on 12-lead
recordings made prior to dosing with Genz-644282.

- Have a systemic fungal, bacterial, viral, or other infection that is not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement) despite appropriate antibiotics or other treatment.

- Have any other severe concurrent disease or a history of serious organ dysfunction or
disease involving the heart, kidney, liver, or other organ system that may place the
patient at undue risk to undergo chemotherapy.

- A known diagnosis of human immunodeficiency virus (HIV) infection or acquired immune
deficiency syndrome (AIDS) or viral hepatitis B or C.

- Presence of ≥ Grade 2 peripheral neuropathy.

- Pregnant or lactating women, due to the unknown effects of Genz-644282 on the
developing fetus or newborn infant.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the Maximum Tolerated Doses for the 28-day and 21-day dosing schedules

Outcome Time Frame:

24 Months

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

July 2009

Completion Date:

January 2013

Related Keywords:

  • Solid Tumors
  • Genz-644282
  • Topoisomerase I inhibitors
  • Top1
  • solid tumors
  • dose-escalation
  • pharmacokinetic (PK)
  • MTD (Maximum Tolerated Dose)
  • oncology
  • cancer
  • Neoplasms



Cancer Institute of New Jersey New Brunswick, New Jersey  08901
Moffitt Cancer Center Tampa, Florida  33612
TGen Clinical Research Services at Scottsdale Healthcare Scottsdale, Arizona  85258
Wayne State University, Division of Hematology/Oncology, Karmanos Cancer Institute Detroit, Michigan