A Phase 1 Multi-Center, Dose Escalation and Pharmacokinetic Study of L-NDDP (Aroplatin) in Patients With Advanced Solid Malignancies or B-Cell Lymphoma
18 Years
N/A
Both
Malignancies, B-Cell Lymphoma
Trial Information
A Phase 1 Multi-Center, Dose Escalation and Pharmacokinetic Study of L-NDDP (Aroplatin) in Patients With Advanced Solid Malignancies or B-Cell Lymphoma
This is a dose escalation study that utilizes a constant incremental dose increase of 50
mg/m2 per cohort. Patients will be enrolled in cohorts of three patients each, and
escalation of dose to the next cohort will be determined based on dose-limiting toxicity
(DLT) in the previous cohort. DLT is defined as any adverse event (AE) of severity grade
3, 4 or 5 (including serious or life-threatening) considered possibly, probably or
definitely related to L-NDDP (CTCAE v3.0), which occurs during cycle 1, excluding those
events that occur and are completely resolved within 4-6 hours of the first dose of L-NDDP
(infusion-related reactions). This study also aims to identify the maximum tolerated dose
(MTD) of intravenous L-NDDP, defined as the dose level at which no more than one out of six
patients has any DLT. Once the MTD has been determined, an additional four patients will be
enrolled at that dose level (for a total of 10 patients at the MTD dose level). While the
MTD is determined based on safety data from each cohort's first cycle of L-NDDP therapy
only, patients may continue treatment with additional cycles of L-NDDP at the same dose as
their starting dose until documented progression, unacceptable toxicity or another off study
criterion is met. Patients who have not met any of the off study criteria and continue to
receive L-NDDP therapy at the time when MTD is determined may be allowed to change L-NDDP
dose to the MTD dose level. The study will also determine the pharmacokinetic profile of
L-NDDP administration through whole blood, plasma, and urine samples drawn before, during,
and after L-NDDP administration. Clinical activity of L-NDDP in solid tumor patients will be
assessed as tumor response using the RECIST criteria. Clinical activity of L-NDDP in B-Cell
lymphoma patients will be assessed using the International Working Group Recommendations.
Inclusion Criteria:
1. Advanced solid malignancies or B-cell lymphoma
2. Less than or equal to 5 anti-cancer treatment regimens, which must be concluded at
least four weeks prior to the first planned L-NDDP administration
3. Measurable disease
4. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
5. New York Heart Association (NYHA) Class I or II
6. Greater than or equal to 18 years of age
7. Absolute neutrophil count greater than or equal to 1.5 x 10^9/L
8. Platelets greater than or equal to 100 x 10^9/L
9. Creatinine less than or equal to 1.5 x upper limit of normal (ULN)
10. ALT less than 3 x ULN in absence of liver metastases; less than 5 x ULN in presence
of liver metastases.
11. Hemoglobin greater than or equal to 10 g/dL
12. Total bilirubin less than or equal to 2 x ULN
13. Female of childbearing potential must have a negative serum pregnancy test
14. Male or female patients of child producing potential must agree to use contraception
or avoidance of pregnancy measures during the study and for one month after the last
L-NDDP dose.
15. Signed written informed consent must be obtained and documented according to ICH-GCP,
the local regulatory requirements, and the rules followed at each institution.
Exclusion Criteria:
1. Known active or untreated brain metastases
2. Other ongoing systemic cancer therapies
3. Hypersensitivity to platinum compounds
4. Other active malignancies with the exception of adequately treated in-situ carcinoma
of the uterine cervix, or non-melanoma skin cancer
5. A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration [at
least two assessments at a minimum of 48 hours apart] of a QTc interval of > 450 for
males and > 470 for females) or history of additional risk factors for torsades des
pointes or use of concomitant medication prolonging the QT/QTc interval
6. Serious illness which, in the opinion of the Principal Investigator, would prevent
study completion
7. Investigational therapy currently or within four weeks prior to planned first dose of
L-NDDP
8. Women who are pregnant or breastfeeding will be excluded from participation.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the maximum tolerated dose and dose-limiting toxicity of L-NDDP
Authority:
United States: Food and Drug Administration
Study ID:
C-726-05
NCT ID:
NCT00316511
Start Date:
March 2006
Completion Date:
Related Keywords:
- Malignancies
- B-Cell Lymphoma
- advanced solid malignancies
- B-cell lymphoma
- Aroplatin
- L-NDDP
- MTD
- advanced solid malignancies or B-cell lymphoma
- Neoplasms
- Lymphoma
- Lymphoma, B-Cell
Name | Location |
|---|---|
| Austin, Texas 78705 | |
| Boston, Massachusetts |
