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

Alternate Title

TLK286 Compared With Either Liposomal Doxorubicin or Topotecan as Third-Line Therapy in Treating Patients With Platinum-Refractory or Platinum-Resistant Metastatic Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03087 TLK-286.3017, NCT00078884

Objectives

Primary

1. Compare survival of patients with platinum-refractory or -resistant metastatic ovarian epithelial, fallopian tube, or primary peritoneal cancer treated with TLK286 vs active control therapy comprising doxorubicin HCl liposome or topotecan as third-line therapy.

Secondary

1. Compare the safety profiles of these regimens in these patients.
2. Compare time to tumor progression in patients treated with these regimens.

Tertiary

1. Compare the objective response rate (complete and partial response) in patients treated with these regimens.
2. Compare time to objective tumor response in patients treated with these regimens.
3. Compare duration of response in patients treated with these regimens.
4. Determine the pharmacokinetics of TLK286 in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cancer
  • The following histologies are eligible:
    • Serous papillary
    • Endometrioid
    • Mucinous
    • Clear cell
    • Poorly differentiated adenocarcinoma
    • Mixtures of the above
  • No sarcomatous, stromal, or germ cell cancers
• Metastatic disease
• Measurable disease
  • Pleural effusions, ascites, osseus metastases, CA125 tumor markers, and lesions in previously irradiated areas are not considered measurable
• Platinum-refractory or -resistant* disease

   [Note: *Platinum-resistant defined as disease recurrence within 6 months of completion of platinum-based chemotherapy OR recurrence after 6 months and failed re-induction with platinum-based chemotherapy]

• Failed 1, and only 1, second-line treatment with doxorubicin HCl liposome OR topotecan for advanced metastatic disease
  • Documented tumor progression within the past 3 months OR unresponsive to treatment
• No known history of CNS metastasis except under the following conditions:
  • Treated with surgery or radiotherapy
  • Neurologically stable
  • No requirement for oral or IV corticosteroids or anticonvulsants
• No leptomeningeal metastases or carcinomatous meningitis

Prior/Concurrent Therapy:

Biologic therapy

• More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
• More than 3 weeks since prior immunotherapy (e.g., interferon) and recovered
• No prior bone marrow transplantation or stem cell support
• Prior anticancer biologic investigational agents allowed
• No concurrent biological response modifiers, except epoetin alfa

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy and recovered
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 3 weeks since prior anticancer hormonal therapy, including anti-estrogens (e.g., tamoxifen)
• No concurrent anticancer hormonal agents (e.g., tamoxifen)

Radiotherapy

• See Disease Characteristics
• More than 3 weeks since prior radiotherapy or radiopharmaceuticals (e.g., phosphorus P32) and recovered
• More than 12 months since prior whole pelvis radiotherapy
• No concurrent radiotherapy except for brain metastases or bone metastases pain control
  • Radiotherapy field must not encompass exposure to the bladder

Surgery

• See Disease Characteristics
• More than 3 weeks since prior major surgery (except for minor biopsy or venous access device placement) and recovered

Other

• More than 2 weeks since prior blood transfusion
• More than 3 weeks since prior investigational drugs
• No prior investigational cytotoxic drugs
  • Prior cytostatic investigational agents allowed
• No other concurrent investigational agents

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Hemoglobin at least 9 g/dL
• Platelet count at least 100,000/mm³

Hepatic

• ALT no greater than 3 times upper limit of normal (ULN) (5 times ULN if hepatic metastases are present)
• Alkaline phosphatase no greater than 5 times ULN (except when bone metastases are present without liver disorder)
• Bilirubin no greater than 2 mg/dL (unless Gilbert's syndrome is clearly documented and other liver function tests are normal)

Renal

• Creatinine no greater than 2 mg/dL

  OR

• Creatinine clearance at least 60 mL/min
• No uncontrolled hypercalcemia (calcium at least 11.5 mg/dL)
• No gross hematuria

Cardiovascular

• No New York Heart Association class II-IV cardiac disease
• No unstable angina within the past 6 months
• No symptomatic ventricular arrhythmias
• No congestive heart failure
• No myocardial infarction within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study treatment
• No intestinal obstruction that would interfere with nutrition
• No history of uncontrolled seizures
• No central nervous system disorders
• No concurrent uncontrolled bacterial or viral infection
• No psychiatric disorder that would preclude study compliance
• No comorbidity that would preclude study participation
• No other malignancy within the past 3 years except adequately treated carcinoma in situ of the cervix, incidental stage endometrial cancer, or basal cell or squamous cell skin cancer

Expected Enrollment

A total of 440 patients (220 per treatment arm) will be accrued for this study within 15 months.

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to prior second-line therapy (doxorubicin vs topotecan), presence of bulky disease* (yes vs no), and ECOG performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

 [Note: *Bulky disease is defined as the presence of a tumor mass at least 5 cm.]

• Arm I: Patients receive TLK286 IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II (active control arm): Patients receive chemotherapy comprising 1 of the following regimens:
  • Patients receive doxorubicin HCl liposome IV over 1 hour on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Patients receive topotecan IV over 30 minutes on days 1-5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

David R. Spriggs, MD, Protocol chair		Ph: 212-639-2203; 800-525-2225

Registry Information
Official Title		Phase III Randomized Study Of TLK286 Versus Doxil®/Caelyx® Or Hycamtin® As Third-Line Therapy In Platinum Refractory Or Resistant Ovarian Cancer
Registered in ClinicalTrials.gov		NCT00078884
Date Submitted to PDQ		2004-01-12
Information Last Verified		2005-05-05
NCI Grant/Contract Number		CA08748

Back to Top