Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Edotecarin and Cisplatin in Treating Patients With Advanced or Metastatic Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03070 PHARMACIA-EDOAES-2730-001, NCT00072332

Objectives

Primary

1. 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

1. Determine the safety profile of this regimen in these patients.
2. Determine the plasma pharmacokinetics of this regimen in these patients.
3. Determine the antitumor activity of this regimen in these patients.

Entry 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

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]

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

A maximum of 80 patients (40 per schedule) will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

David Ilson, MD, PhD, Principal investigator		Ph: 212-639-8306; 800-525-2225

Registry Information
Official Title		A Phase I Dose Escalation Study of Edotecarin (PHA-782615) and Cisplatin in Adult Patients with Advanced/Metastatic Solid Tumors
Trial Start Date		2003-08-12
Registered in ClinicalTrials.gov		NCT00072332
Date Submitted to PDQ		2003-09-30
Information Last Verified		2005-08-18
NCI Grant/Contract Number		P30-CA08748

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