A Phase I Dose Escalation Study of Edotecarin (PHA-782615) and Cisplatin in Adult Patients With Advanced/Metastatic Solid Tumors
18 Years
N/A
Both
Esophageal Cancer, Gastric Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Dose Escalation Study of Edotecarin (PHA-782615) and Cisplatin in Adult Patients With Advanced/Metastatic Solid Tumors
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended phase II dose of edotecarin when
administered with cisplatin (administered in 2 different schedules) in patients with
advanced or metastatic solid tumors.
Secondary
- Determine the safety profile of this regimen in these patients.
- Determine the plasma pharmacokinetics of this regimen in these patients.
- Determine the antitumor activity of this regimen in these patients.
OUTLINE: This is an open-label, multicenter, dose-escalation study of edotecarin. Patients
are assigned to 1 of 2 schedules.
- Schedule A: Patients receive cisplatin IV over 30 minutes and edotecarin IV over 1 hour
on days 1 and 8.
- Schedule B: Patients receive cisplatin IV over 2 hours and edotecarin IV over 1 hour on
day 1.
In both schedules, courses repeat every 3 weeks in the absence of disease progression or
unacceptable toxicity.
Cohorts of 3-6 patients in each schedule receive escalating doses of edotecarin until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is
determined, 10 additional patients with metastatic esophageal or gastric cancer receive
treatment as above at the MTD.
Patients are followed every 2 months for 1 year or until disease progression.
PROJECTED ACCRUAL: A maximum of 80 patients (40 per schedule) will be accrued for this
study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of one of the following:
- Histologically or cytologically confirmed active solid tumor malignancy
- Histologically confirmed esophageal or gastric cancer* meeting all the following
criteria:
- Previously untreated disease
- Metastatic disease
- Measurable disease
- At least 1 unidimensionally measurable lesion at least 20 mm by
conventional techniques OR 10 mm by spiral CT scan NOTE: *Patients
with esophageal or gastric cancer are enrolled after the maximum
tolerated dose has been determined
- No known brain or leptomeningeal disease
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9.0 g/dL
Hepatic
- Bilirubin no greater than 1.5 times upper limit of normal (ULN) (regardless of liver
involvement by tumor)
- SGOT no greater than 3 times ULN (5 times ULN if there is liver involvement by tumor)
- Albumin at least 3.0 g/dL
Renal
- Creatinine no greater than 1.5 mg/dL
Cardiovascular
- None of the following within the past 12 months:
- Myocardial infarction
- Severe/unstable angina
- Symptomatic congestive heart failure
- Cerebrovascular accident
- Transient ischemic attack
- Deep vein thrombosis
- Other significant thromboembolic event
- No ongoing grade 2 or greater cardiac dysrhythmia
- No atrial fibrillation
Pulmonary
- No pulmonary embolism within the past 12 months
Gastrointestinal
- No active inflammatory bowel disease
- No partial or complete bowel obstruction
- No chronic diarrhea
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No grade 2 or greater acute toxic effects
- No active infection
- No other concurrent acute or chronic medical or psychiatric condition or laboratory
abnormality that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior treatment with any of the following systemic therapies for metastatic
cancer*:
- Antibody therapy
- Immunotherapy
- Gene therapy
- Vaccine therapy
- Cytokine therapy
- Inhibitors of vascular endothelial growth factor/Flk-1 pathway
- No concurrent sargramostim (GM-CSF)
- No concurrent antibody therapy or immunotherapy NOTE: *Patients with esophageal or
gastric cancer only
Chemotherapy
- No more than 1 prior chemotherapy regimen for metastatic disease*
- No prior high-dose chemotherapy requiring hematopoietic stem cell rescue
- No other concurrent chemotherapy NOTE: *No prior chemotherapy for metastatic disease
for patients with esophageal or gastric cancer
Endocrine therapy
- No concurrent hormonal treatment
Radiotherapy
- No prior radiotherapy to more than 25% of bone marrow reserve
- No prior radiotherapy to the sole measurable lesion*
- No concurrent radiotherapy NOTE: *Patients with esophageal or gastric cancer only
Surgery
- More than 12 months since prior coronary/peripheral artery bypass graft surgery
Other
- Recovered from prior therapy
- More than 6 months since last dose of prior adjuvant therapy*
- No prior treatment with any of the following systemic therapies for metastatic
cancer*:
- Cyclooxygenase-2 inhibitors
- Matrix metalloprotease inhibitors
- Epidermal growth factor receptor inhibitors
- Other experimental agents
- No other concurrent anticancer therapy
- No concurrent enrollment in another clinical trial
- No other concurrent experimental drugs NOTE: *Patients with esophageal or gastric
cancer only
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
David H. Ilson, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000339607
NCT ID:
NCT00072332
Start Date:
August 2003
Completion Date:
Related Keywords:
- Esophageal Cancer
- Gastric Cancer
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- stage IV esophageal cancer
- stage IV gastric cancer
- Esophageal Diseases
- Esophageal Neoplasms
- Stomach Neoplasms
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
