Irinotecan and Thalidomide in Treating Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: irinotecan hydrochloride; Drug: thalidomide; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00062127

NCI-2012-02537

U01CA069852 (U.S. NIH Grant/Contract)

12044B

CDR0000304517 (Registry Identifier)

Details and patient eligibility

About

Thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Drugs used in chemotherapy such as irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with irinotecan may kill more tumor cells. This randomized phase I trial is studying the side effects and best way to give irinotecan and thalidomide in treating patients with metastatic or unresectable solid tumors

Full description

PRIMARY OBJECTIVES:

I. Determine whether thalidomide alters the pharmacokinetics of irinotecan in patients with advanced solid tumors.

II. Determine whether irinotecan alters the pharmacokinetics of thalidomide in these patients.

III. Determine the toxicity of this regimen in these patients. IV. Determine the observed antitumor response in patients treated with this regimen.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive irinotecan IV over 90 minutes on days 1 and 22 and oral thalidomide once daily on days 15-28.

Arm II: Patients receive irinotecan as in arm I and oral thalidomide once daily on days -6 to 7.

All patients undergo disease re-evaluation at 6 weeks. Patients with stable or responsive disease may receive additional courses comprising irinotecan IV on day 1 and oral thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed malignant solid tumor

  • Metastatic or unresectable
  • Standard curative or palliative therapy is no longer effective or does not exist

• Measurable or assessable disease

• No uncontrolled brain metastases

  • Patients with brain metastases are eligible provided the following are true:

    • Stable neurologic status
    • At least 4 weeks since prior steroids or anticonvulsants
    • No neurologic dysfunction that would confound evaluation

• Performance status - Karnofsky 70-100%

• More than 12 weeks

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin normal

• AST and ALT no greater than 2.5 times upper limit of normal

• Creatinine normal

• Creatinine clearance at least 60 mL/min

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No history of inflammatory bowel disease requiring therapy

• No chronic diarrhea syndromes

• No paralytic ileus

• Not pregnant or nursing

• Negative pregnancy test

• Fertile female patients must use 2 forms of effective contraception, including 1 highly effective method, for at least 4 weeks before, during, and for 4 weeks after study participation

• Male patients must use effective barrier contraception during and for 4 weeks after study participation

• No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs

• No uncontrolled seizure disorder

• No other concurrent uncontrolled illness that would preclude study participation

• No psychiatric illness or social situation that would preclude study compliance

• No ongoing or active infection

• No significant traumatic injury within the past 28 days

• No serious, nonhealing wounds or ulcers

• No bone fractures

• No preexisting peripheral neuropathy grade 2 or greater

• At least 4 weeks since prior biologic therapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy

• More than 28 days since prior major surgical procedure or open biopsy

• At least 4 weeks since prior investigational therapy

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational or commercial agents or therapies for the malignancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

Arm I (irinotecan hydrochloride and thalidomide)

Experimental group

Description:

Patients receive irinotecan IV over 90 minutes on days 1 and 22 and oral thalidomide once daily on days 15-28. All patients undergo disease re-evaluation at 6 weeks. Patients with stable or responsive disease may receive additional courses comprising irinotecan IV on day 1 and oral thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: pharmacological study

Drug: thalidomide

Drug: irinotecan hydrochloride

Arm II (irinotecan hydrochloride and thalidomide)

Experimental group

Description:

Patients receive irinotecan as in arm I and oral thalidomide once daily on days -6 to 7. All patients undergo disease re-evaluation at 6 weeks. Patients with stable or responsive disease may receive additional courses comprising irinotecan IV on day 1 and oral thalidomide once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: pharmacological study

Drug: thalidomide

Drug: irinotecan hydrochloride