Clinical trial NCT00871663: Phase 1 Weekly Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04629AM6)
Official title: A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Cyclin-Dependent Kinase (CDK) Inhibitor SCH 727965 Administered Weekly in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lymphoma, Non-Hodgkin
Multiple Myeloma
Leukemia, Lymphocytic, Chronic. B-Cell
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-03-30
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety, tolerability, maximum administered dose, and dose limiting toxicity of SCH 727965 administered as an intravenous infusion on Days 1, 8 and 15 of each 28 day cycle in participants with solid tumors, non Hodgkins lymphoma, multiple myeloma or chronic lymphocytic leukemia.


Eligibility criteria: Inclusion Criteria:

* Age \>=18 years, either sex, any race.
* Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
* There must be no known standard therapy, or disease must be refractory to standard therapy
* Adequate hematologic, renal, and hepatic organ function and laboratory parameters
* For advanced solid tumors, non-Hodgkin's lymphoma, or multiple myeloma:

  * Participants must have histologically proven solid tumors, non-Hodgkin's lymphoma, or multiple myeloma.
  * Evaluable malignancy must be present by computed tomography or magnetic resonance imaging, obtained within 4 weeks prior to the start of treatment with SCH 727965.
* Subjects with multiple myeloma must have measurable disease defined as:

  * Serum monoclonal protein greater than 0.5 g/dL or urine light chain excretion of greater than 0.2 g/24-hour obtained within 4 weeks prior to the start of treatment.
  * Participants with lower M protein values or nonsecretory myeloma are eligible if measurable disease can be established within 4 weeks prior to start of treatment, such as:

    * serum free light chain ratio greater than 5 times the normal ratio limit; and/or
    * measurable soft tissue plasmacytoma greater than 2 cm, by either physical examination and/or applicable radiographs; and/or
    * bone marrow involvement greater than 30%.
* For B-cell chronic lymphocytic leukemia (B-CLL):

  * Diagnosis of B-CLL according to the National Cancer Institute Working Group (NCI-WG) criteria or a histological diagnosis of small lymphocytic lymphoma.
  * Disease must be evaluable according to NCI-WG response criteria.

Exclusion Criteria:

* Symptomatic brain metastases or primary central nervous system malignancy.
* Previous radiation therapy to \>25% of the total bone marrow.
* Previous treatment with SCH 727965.
* Known HIV infection.

Primary outcomes:
measure: Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity.
timeFrame: End of trial
measure: In participants with advanced solid tumors, non Hodgkin's lymphoma or multiple myeloma, pharmacodynamic effects of SCH 727965 with an ex vivo lymphocyte stimulation assay of participant's peripheral blood lymphocytes.
timeFrame: End of trial
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Flynn J, Jones J, Johnson AJ, Andritsos L, Maddocks K, Jaglowski S, Hessler J, Grever MR, Im E, Zhou H, Zhu Y, Zhang D, Small K, Bannerji R, Byrd JC. Dinaciclib is a novel cyclin-dependent kinase inhibitor with significant clinical activity in relapsed and refractory chronic lymphocytic leukemia. Leukemia. 2015 Jul;29(7):1524-9. doi: 10.1038/leu.2015.31. Epub 2015 Feb 24.
citation: Nemunaitis JJ, Small KA, Kirschmeier P, Zhang D, Zhu Y, Jou YM, Statkevich P, Yao SL, Bannerji R. A first-in-human, phase 1, dose-escalation study of dinaciclib, a novel cyclin-dependent kinase inhibitor, administered weekly in subjects with advanced malignancies. J Transl Med. 2013 Oct 16;11:259. doi: 10.1186/1479-5876-11-259.