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A Phase 1 Study of Topotecan Liposomes Injection (TLI) in Subjects With Small Cell Lung Cancer (SCLC), Ovarian Cancer and Other Advanced Solid Tumors

Phase 1
18 Years
Open (Enrolling)
Small Cell Lung Cancer, Ovarian Cancer, Solid Tumors

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Trial Information

A Phase 1 Study of Topotecan Liposomes Injection (TLI) in Subjects With Small Cell Lung Cancer (SCLC), Ovarian Cancer and Other Advanced Solid Tumors

The study will utilize an accelerated design with small initial cohort sizes that allow
fewer subjects to be enrolled at sub-therapeutic doses such as the very low starting doses
in both arms of the study. Initial cohorts will include only one subject and dose
escalations will be in 100% increments until a single Grade 2 toxicity related to study drug
or DLT occurs in Cycle 1. Dose escalation will proceed until the MTD is exceeded. MTD is
defined as average of the highest dose level for which 2 out of 6 subjects experience a DLT
and the previous dose level, provided no additional DLTs occur. Subjects who discontinue
TLI treatment before completion of Cycle 1 for reasons other than toxicity will not be
evaluable for the determination of MTD and will be replaced.

The study will consist of a screening period, treatment period, and a post-treatment period.
Subjects will be followed for 30 days after their last TLI dose. Safety and tolerability
parameters include clinical laboratory assessments, vital signs, physical examinations, and
adverse events (AEs).

Inclusion Criteria:

1. Age ≥ 18 years

2. Histologically or cytologically confirmed advanced solid tumor that has relapsed, is
refractory to standard treatment, or for whom there is no standard therapy available.

3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

4. Normal organ and marrow function as defined below within 14 days of study entry

1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

2. Platelet count ≥100 x 109/L

3. Hemoglobin ≥ 9 g/dL

4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x
upper limit of normal (ULN), or 5 x ULN for subjects with liver metastases

6. Serum creatinine ≤ 1.5 x ULN or calculated estimated creatinine clearance ≥ 50
mL/min/1.73m2 for subjects with creatinine levels above institutional normal
based on the Cockcroft and Gault formula.

5. Never received prior TLI or topotecan HCl (Hycamtin®)

6. At least 4 weeks must have elapsed from the last dose of chemotherapy.

7. Life expectancy ≥ 3 months

8. Women of childbearing potential must have a negative urine or blood pregnancy test
within 7 days prior to initiation of treatment.

9. If female, subject is post-menopausal, surgically sterilized, or willing to use
acceptable methods of birth control (e.g., hormonal contraceptive, intra-uterine
device (IUD), diaphragm with spermicide, condom with spermicide or abstinence) from
the screening visit through the duration of study participation.

10. If male, subject agrees to use an acceptable barrier method for contraception from
the screening visit though the duration of study participation.

11. Before enrollment, the subject is capable of understanding and complying with
parameters as outlined in the protocol and able to sign a written informed consent
according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

1. Use of any investigational drugs, biologics, or devices within 28 days prior to study
treatment or planned use during the course of the study.

2. Primary tumors of central nervous system (CNS). Symptomatic brain metastases (unless
subject is stable without requirement of steroids and/or antiseizure medications for
at least three months) or leptomeningeal tumor involvement. Imaging studies are not
required to rule this out unless there is a clinical suspicion of CNS disease.

3. Prior chemotherapy or radiotherapy within 4 weeks of Day 1 of study (6 weeks for
nitrosureas or mitomycin C).

4. Planned concurrent systemic therapy (cytotoxic and/or cytostatic) and/or radiotherapy
during study treatment.

5. Less than 4 weeks have elapsed from the time of major surgery.

6. Subjects with a history of allergic reactions or sensitivity attributed to compounds
of similar chemical or biologic composition to TLI, including known allergies to the
ingredients comprising the liposome (e.g., cholesterol and/or sphingomyelin), which
in the Investigator's opinion may put the subject at risk for significant reaction to
the study drug.

7. Subjects who are pregnant or lactating.

8. Subjects known to be positive for human immunodeficiency virus (HIV), hepatitis C
antibody, or hepatitis B surface antigen.

9. Prophylactic hematologic growth factors administered ≤ 2 weeks prior to start of
treatment with TLI (excluding darbepoetin alfa and epoetin alfa).

10. Active infection or any serious underlying medical condition, which would impair the
ability of the subject to receive protocol treatment.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluate the safety, tolerability and maximum tolerated dose of 2 different dosing schedules of TLI administered intravenously

Outcome Time Frame:

21 days following initial dose

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2008

Completion Date:

December 2013

Related Keywords:

  • Small Cell Lung Cancer
  • Ovarian Cancer
  • Solid Tumors
  • Other Advanced Solid Tumors
  • Lung Neoplasms
  • Ovarian Neoplasms
  • Small Cell Lung Carcinoma
  • Neoplasms



South Texas Accelerated Research TherapeuticsSan Antonio, Texas  78229
Barbara Ann Karmanos Cancer CenterDetroit, Michigan  48201