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


Phase 1
18 Years
N/A
Not Enrolling
Both
Esophageal Cancer, Gastric Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Thank you

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 CenterNew York, New York  10021