XK469 in Treating Patients With Advanced Solid Tumors

Phase I Study of R(+)-XK469 (NSC 698215) Given Daily, Days 1-5, Repeated Every Three Weeks in Patients With Advanced Malignancies

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of XK469 in treating patients who have advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: R(+)XK469

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose, dose-limiting toxicity, and recommended phase II dose of XK469 in patients with advanced solid tumors.
• Determine the safety of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.
• Determine, preliminarily, any anti-tumor activity of this drug in these patients.
• Determine the drug metabolism, drug interaction potential, molecular and cellular predictors of efficacy and toxicity, and clinical confirmation of molecular responses in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive XK469 IV over 20 minutes on days 1-5. Treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of XK469 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of the first 6 patients experience dose-limiting toxicity.

Once the MTD is determined, up to 15 patients are treated at that dose. Patients in the expanded MTD cohort also receive oral NovaSoy® soybean extract twice daily for the study duration.

Patients are followed every 4 weeks.

PROJECTED ACCRUAL: Approximately 25-40 patients will be accrued for this study within 12-15 months.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-hematological cancer that is unresponsive to available therapies or for which there is no known effective treatment

• Measurable or evaluable disease

  • Clinical or radiological evidence of disease required
• No active brain metastases

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT and AST no greater than 2.5 times upper limit of normal

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• Ejection fraction at least 50%
• No significant arrhythmias
• No congestive heart failure

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No dementia or altered mental status
• No known HIV infection
• No active infection
• No other serious uncontrolled medical disorder that would preclude study participation
• No known allergies to soy products, rice flour, or gelatin (if receiving study dietary soy supplementation)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy
• No concurrent prophylactic colony-stimulating factors

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• Prior taxanes allowed
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except hormone replacement therapy or medication used to maintain castrate status for patients with progressive hormone-refractory prostate cancer

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of bone marrow-containing areas
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• At least 4 weeks since prior investigational agents
• No other concurrent experimental anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XK469	Drug: R(+)XK469

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): April 25, 2014
• Last Update Submitted That Met QC Criteria: April 24, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Other Study ID Numbers: CDR0000069103; P30CA022453 (U.S. NIH Grant/Contract); U01CA062487 (U.S. NIH Grant/Contract); WSU-C-2346; NCI-4550; WSU-T-2001