Brief Title
Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy
Official Title
Phase II Clinical and Pharmacokinetic Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy
Brief Summary
This study is a phase II clinical and pharmacokinetic trial of PM00104 (Zalypsis®) in
patients with advanced and/or metastatic endometrial or cervical cancer previously treated
with one line of systemic chemotherapy to evaluate the antitumor activity and to determine
the safety profile, the pharmacokinetic profile and the pharmacogenomic profile.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
To evaluate antitumor activity of PM00104 administered as intravenous infusion to patients with advanced and/or metastatic endometrial or cervical cancer previously treated with one line of systemic chemotherapy.
Secondary Outcome
To determine the safety profile, the pharmacokinetic (PK) profile and the pharmacogenomic profile to patients with advanced and/or metastatic endometrial or cervical cancer previously treated with one line of systemic chemotherapy.
Condition
Uterine Cervical Cancer
Intervention
Zalypsis ( PM00104)
Study Arms / Comparison Groups
Arm 1
Description: Zalypsis (PM00104)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
19
Start Date
August 2009
Completion Date
September 2011
Primary Completion Date
September 2011
Eligibility Criteria
Inclusion Criteria:
1. Voluntary written informed consent, obtained from the patient before the beginning of
any specific study procedures.
2. Group 1 (endometrial cancer):
- Histologically confirmed advanced and/or metastatic endometrial cancer (any
grade, including endometrioid, clear cell, serous and mixed types) with
documented disease progression as per RECIST at study entry.
- Patients must have failed one prior systemic chemotherapy line for
advanced/metastatic disease (excluding chemosensitizing chemotherapy); prior
hormone therapy and biological therapy are allowed.
3. Group 2 (cervical cancer):
- Histologically confirmed advanced and/or metastatic cervical cancer with
documented disease progression as per RECIST at study entry.
- Patients must have failed one prior systemic chemotherapy line for
advanced/metastatic disease (excluding chemosensitizing chemotherapy); prior
hormone therapy and biological therapy are allowed.
4. Complete recovery from the effects of prior radiotherapy and from any drug-related
adverse events (AEs) derived from previous treatments, excluding alopecia and grade 1
peripheral neuropathy according to the National Cancer Institute Common Terminology
Criteria for Adverse Events (NCICTCAE, v.3.0).
5. At least one measurable lesion ("target lesion" according to the RECIST), located in a
non-irradiated area and adequately measured less than four weeks before study entry.
Tumors within a previously irradiated field will be designated as "nontarget" lesions
unless progression is clearly documented or biopsy proven.
6. Age ≥ 18 years.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
8. Life expectancy ≥ 3 months.
9. Appropriate bone marrow reserve, renal and hepatic functions:
- Platelet count ≥ 100 x 109/l, hemoglobin ≥ 9 g/dl and absolute neutrophil count
(ANC) ≥ 1.5 x 109/l.
- Alkaline phosphatase (AP) ≤ 2.5 x upper limit of normality (ULN) (≤ 5 x ULN in
case of extensive bone metastases).
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5
x ULN in case of hepatic metastases).
- Total bilirubin ≤ 1.5 x ULN, unless due to Gilbert's syndrome.
- Renal function: patients with calculated creatinine clearance (using Cockcroft
and Gault formula) ≥ 30 ml/min.
- Albumin ≥ 2.5 g/dl.
10. Left ventricular ejection fraction (LVEF) within normal limits (LVEF of at least 50%).
11. Women of childbearing potential must have a negative serum pregnancy test before study
entry. In case of childbearing potential, the patients and their partners must agree
to use a medically acceptable method of contraception.
Exclusion Criteria:
1. Prior therapy with PM00104.
2. Uterine sarcomas, adenosarcoma, and malignant Mullerian tumors.
3. Cervical neuroendocrine or small cell carcinomas, nonepithelial cervical neoplasms
such as sarcomas.
4. Patients who have isolated recurrences (vaginal, pelvic or paraaortic) potentially
curative with radiation therapy or surgery.
5. Pregnant or lactating women, or in case of childbearing potential, women not using an
appropriate contraceptive method.
6. Less than three weeks from prior radiation therapy, biological therapy or
chemotherapy, AND
- Less than six weeks from prior nitrosourea, mitomycin C, high-dose chemotherapy
or radiotherapy involving the whole pelvis or over 50% of the spine, provided
that acute effects of radiation treatment have resolved.
- Hormonal therapy and palliative radiation therapy (i.e., for control of pain from
bone metastases) must be discontinued before study entry.
7. Group 1 (endometrial cancer): more than one line of prior systemic chemotherapy for
advanced/metastatic disease (excluding chemosensitizing chemotherapy), but not less
than three weeks before.
8. Group 2 (cervical cancer): more than one line of prior systemic chemotherapy for
advanced/metastatic disease (excluding chemosensitizing chemotherapy, but not less
than three weeks before.
9. Patients with a prior invasive malignancy (except nonmelanoma skin cancer) who have
had any evidence of disease within the last five years or whose prior malignancy
treatment contraindicates the current protocol therapy.
10. Patients with serious non-healing wound, ulcer, or bone fracture.
- This includes history of: abdominal fistula, gastrointestinal perforation or
intra-abdominal abscess for which an interval of three to six months must pass
before study entry.
- In addition, the patient must have undergone correction (or spontaneous healing)
of the perforation/fistula and/or the underlying process causing the
fistula/perforation.
- Patients with granulating incisions healing by secondary intention with no
evidence of fascial dehiscence or infection are eligible but require weekly wound
examinations.
11. Evidence of progressive or symptomatic central nervous system (CNS) metastases or
leptomeningeal metastases.
12. Other diseases or serious conditions:
- Increased cardiac risk as defined by:
- Unstable angina or myocardial infarction within 12 months before inclusion
in the study.
- New York Heart Association (NYHA) grade II or greater congestive heart
failure.
- Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment.
- Abnormal electrocardiogram (ECG), i.e., patients with the following are
excluded: QT prolongation - QTc > 480 msec; signs of cardiac enlargement or
hypertrophy; bundle branch block; partial blocks;signs of ischemia or
necrosis, and Wolff Parkinson White patterns.
- History or presence of valvular heart disease.
- Uncontrolled arterial hypertension despite optimal medical therapy.
- Previous mediastinal radiotherapy.
- Previous treatment with doxorubicin at cumulative doses exceeding 400 mg/m2.
- History of significant neurological or psychiatric disorders.
- Active infection requiring systemic treatment.
- Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic
hepatitis).
- Immunocompromised patients, including those known to be infected with the human
immunodeficiency virus (HIV).
- Uncontrolled (i.e., requiring relevant changes in medication within the last
month or hospital admission within the last three months) endocrine diseases
(e.g., diabetes mellitus, hypo- or hyperthyroidism, adrenal disorder).
13. Any other major illness that, in the Investigator's judgment, will substantially
increase the risk associated with the patient's participation in the study. The
investigator should feel free to consult the Study Coordinator or the Sponsor for
uncertainty in this regard.
14. Limitation of the patient's ability to comply with the treatment or to follow-up at a
participating center. Patients enrolled into this trial must be treated and followed
at a participating center.
15. Treatment with any investigational product within 30 days prior to inclusion in the
study.
16. Known hypersensitivity to any component of PM00104.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00900562
Organization ID
PM104-B-001-09
Responsible Party
Sponsor
Study Sponsor
PharmaMar
Study Sponsor
, ,
Verification Date
January 2013