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A Phase 1 Trial of Escalating Doses of Karenitecin Plus Cyclophosphamide Administered Intravenously Daily for 5 Consecutive Days in Pediatric Patients With Refractory or Recurrent Solid Tumors

Phase 1
12 Months
21 Years
Not Enrolling
Solid Tumors

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Trial Information

A Phase 1 Trial of Escalating Doses of Karenitecin Plus Cyclophosphamide Administered Intravenously Daily for 5 Consecutive Days in Pediatric Patients With Refractory or Recurrent Solid Tumors

This is a Phase 1, open-label, dose-escalating study of karenitecin plus cyclophosphamide in
the treatment of pediatric patients with refractory or recurrent solid tumors. All patients
must have histologically documented diagnosis of cancer (solid tumors) refractory to
conventional therapeutic modalities or for which no curative treatment exists.

Approximately 50 patients will be registered into the study in one of 2 strata.

Stratum 1 will include patients with known bone marrow metastases or those who have had
prior intensive myelosuppression therapy. Stratum 2 will include patients without previous
intensive myelosuppressive therapy or bone marrow metastases. Each stratum will accrue
patients independently.

The primary endpoint in this study is the MTD and determining the recommended Phase 2 dose
level for this study. The MTD will be determined for each stratum independently.

There are 3 defined periods in this study:

Period I (Screening and Registration)

Period II (Active Treatment): An accelerated titration dose escalation design will be used
in this study. Dose escalation will function independently for each stratum.

Period III (End of Study): Once treatment has been discontinued, patients will undergo
end-of-study procedures.

Inclusion Criteria:

1. Age greater than 12 months and less than or equal to 21 years at the time of

2. Histological documentation of cancer (solid tumors) at initial diagnosis. The
requirement for histological verification will be waived for patients with intrinsic
brainstem gliomas. Patients with non-Hodgkin's lymphomas or Hodgkin's Disease are
considered to have non-hematological malignancies.

3. Current disease state must be one which is refractory to curative therapeutic
modalities or for which there is no known curative therapy.

4. Karnofsky score greater than or equal to 60 (patients over 10 years of age) and
Lansky score greater than or equal to 60 (patients 10 years of age or less).
Performance status scales/scores are provided in Appendix E in full protocol attached
in Section S.

Note: Neurological deficits in patients with CNS tumors must have been stable for a
minimum of one week before study entry. Patients who are unable to walk because of
paralysis, but who are up in a wheelchair will be considered ambulatory for
performance score assessment.

5. Fully recovered from any acute toxic effects of all previous chemotherapy,
immunotherapy, biological therapy, or radiotherapy before study entry.

6. At least 90 days must have elapsed after autologous or allogeneic stem cell rescue
(SCR) and the start of study treatment. There should be no evidence of active graft
versus host disease.

7. At least 7 days must have elapsed since the last administration of
non-myelosuppressive chemotherapy, immunotherapy or biological therapy and the start
of study treatment.

8. At least 21 days must have elapsed since the completion of myelosuppressive
chemotherapy and the start of study treatment (at least 42 days must have elapsed if
treated with nitrosourea).

9. At least 14 days must have elapsed since the completion of local palliative external
beam radiotherapy (XRT - small port) and the start of study treatment. At least 6
months must have elapsed if prior total body irradiation (TBI), craniospinal XRT, or
if radiation to 50% or more of pelvis; and at least 42 days must have elapsed if
other substantial bone marrow radiation (20% or more of marrow - see Appendix F).

10. Negative serum or urine pregnancy test (female patients of childbearing potential).

11. Agreed to use an effective contraceptive method, including abstinence (male and
female patients of reproductive potential).

12. Adequate bone marrow function, defined as: • Peripheral absolute neutrophil count
(ANC) 1000/mm3 or greater. • Platelet count 75,000/mm3 or greater (transfusion
independent) for Stratum 1. • Platelet count 100,000/mm3 or greater (transfusion
independent) for Stratum 2. • Hemoglobin 8.0 g/dL or greater (may receive red blood
cell [RBC] transfusions).

13. Adequate renal function; defined as: •Creatinine clearance or radioisotope glomerular
filtration rate (GFR) 70 mL/min/m2 or greater.


• Serum creatinine based on age as follows: 5 years or less - 0.8 or less mg/dL over
5 years to 10 years old - 1.0 or less mg/dL over 10 years to 15 years old - 1.2 or
less mg/dL over 15 years old - 1.5 or less mg/dL

14. Adequate hepatic function; defined as: • Total bilirubin 1.5 mg/dL or less. • ALT 5
or less x upper limit of normal (ULN) for age. • Albumin 2 g/dL or more.

15. Adequate cardiac function; defined as: • No known history of congestive heart
failure. • No uncontrolled medically-important cardiac arrhythmias, including
ventricular tachycardia/fibrillation, atrial fibrillation, flutter or idioventricular

16. Informed consent must be obtained before any study-specific testing is performed or
administration of treatment.

Exclusion Criteria:

1. Are pregnant or breastfeeding.

2. Receiving, or have received growth factors that support platelet count, or white cell
number or function within 7 days of screening blood work.

3. Patients with CNS tumors who have not been on a stable or decreasing dose of
dexamethasone for the past 7 days at the time of screening.

4. Currently receiving treatment with another investigational therapy.

5. Currently receiving treatment with other anti-cancer agents.

6. Have CNS metastases or malignant leptomeningeal involvement that is rapidly
progressive, or have poorly controlled seizures (no more than one seizure/month on
anti-epileptic therapy).

7. Have an active infection (including viral, fungal, bacterial, rickettsial,
mycobacterial, or parasitic).

8. Are judged by the Investigator to be unlikely to be able to fully comply with the
study protocol and/or to complete the study or required study procedures.

Type of Study:


Study Design:

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

Outcome Measure:

To determine the maximum tolerated dose (MTD) levels and recommended Phase 2 dose levels of Karenitecin when administered intravenously for 5 consecutive days with a fixed dose of Cytoxan®

Outcome Time Frame:

evaluation will extend at least 30 days following the last dose or until toxicities have resolved

Safety Issue:


Principal Investigator

Susan Blaney, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Baylor College of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

February 2007

Completion Date:

January 2011

Related Keywords:

  • Solid Tumors
  • solid tumors
  • Neoplasms



Texas Children's Hospital Houston, Texas