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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00072332

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as edotecarin and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining edotecarin with cisplatin may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining edotecarin with cisplatin in treating patients who have advanced or metastatic solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer Gastric Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: cisplatin Drug: edotecarin	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Dose Escalation Study of Edotecarin (PHA-782615) and Cisplatin in Adult Patients With Advanced/Metastatic Solid Tumors

Study Start Date :

Aug 1, 2003

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Dec 1, 2009

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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