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

Alternate Title

Irinotecan Plus Gemcitabine in Treating Patients With Unresectable or Metastatic Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI, Pharmaceutical / Industry NU-98X3 P-UPJOHN-976475157, NCI-G99-1588, NCT00004095

Objectives

1. Determine the maximum tolerated dose (MTD) and the principal toxicities of irinotecan and gemcitabine in patients with surgically unresectable or metastatic solid tumors.
2. Determine if the principal toxicities and MTD of this combination regimen are affected by drug sequencing in this patient population.
3. Determine the potential for gemcitabine to alter the pharmacokinetic characteristics when administered with irinotecan in these patients.
4. Describe the influence effected by varying the administration sequence of this combination regimen in this patient population.
5. Obtain preliminary data regarding efficacy of this combination regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed metastatic or surgically unresectable solid tumor, having received the following maximum number of prior therapies for advanced disease:
  • Bladder cancer - no more than 1 prior therapy
  • Breast cancer - no more than 2 prior therapies
  • Colorectal cancer - no more than 1 prior therapy
  • Kidney cancer - no prior therapy
  • Lung cancer - no more than 1 prior therapy
  • Pancreatic cancer - no prior therapy



• Bidimensionally measurable disease outside a previously irradiated field
  • At least 2 cm x 2 cm



• No known bone metastases



• CNS involvement allowed if successfully controlled by surgery or radiotherapy and not requiring corticosteroids



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent sargramostim (GM-CSF)
• No concurrent immunotherapy

Chemotherapy:

• No prior irinotecan, topotecan, or gemcitabine
• Prior adjuvant chemotherapy allowed, if at least 1 year between last dose of adjuvant chemotherapy and recurrence of cancer
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy to less than 30% of bone marrow
• No prior whole pelvic radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No concurrent phenytoin, phenobarbital, or other antiepileptic prophylaxis

Patient Characteristics:

Age:

• 18 and over

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL regardless of liver involvement secondary to tumor
• SGOT no greater than 3 times upper limit of normal (ULN) (no greater than 5 times ULN if liver metastases present)
• No known Gilbert's disease

Renal:

• Creatinine no greater than 1.8 mg/dL
• Calcium less than 12.0 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy

Other:

• No active uncontrolled bacterial, viral (including HIV), or invasive fungal infection
• No psychiatric disorders that would prevent compliance
• No other malignancy within the past 5 years except adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of seizures
• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

At least 12 patients will be accrued for this study.

Outline

This is a dose-escalation study.

Patients receive irinotecan IV over 90 minutes followed by gemcitabine IV over 30 minutes on days 1 and 15. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the maximum tolerated dose (MTD) is reached, patients receive subsequent doses of the inverse sequence of the combination drugs until a new MTD is determined.

Cohorts of 3-6 patients receive escalating doses of irinotecan and gemcitabine until the MTD is reached. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months until death.

Wisinski KB, Mulcahy MF, Newman S, et al.: A phase I study of irinotecan and gemcitabine in solid tumors. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-140, 2007.

Trial Contact Information

Trial Lead Organizations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Al Benson, MD, FACP, Protocol chair		Ph: 312-695-6180

Registry Information
Official Title		Phase I Trial of Irinotecan (CPT-11) and Gemcitabine in Patients with Solid Tumors
Trial Start Date		1999-08-31
Registered in ClinicalTrials.gov		NCT00004095
Date Submitted to PDQ		1999-09-03
Information Last Verified		2004-04-08
NCI Grant/Contract Number		P30-CA6055

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