Clinical trial NCT00871910: Phase 1 Every-3-Week Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04630)
Official title: A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Cyclin-Dependent Kinase (CDK) Inhibitor SCH 727965 Administered Every 3 Weeks in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lymphoma, Non-Hodgkin
Multiple Myeloma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-03-30
Enrollment: 81
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: Part 1 and Part 2 of this trial will evaluate the safety, tolerability, maximum administered dose, and dose limiting toxicity of SCH 727965 administered every 3 weeks as a 2 hour intravenous (IV) infusion (Part 1), and as an 8-hour or 24-hour IV infusion (Part 2). Each 3-week period is considered one treatment cycle. Part 3 of this trial will evaluate the effect of coadministration of antiemetic drug aprepitant on the pharmacokinetics of SCH 727965 administered as a 2 hour IV infusion once every 3 weeks.


Eligibility criteria: Inclusion Criteria:

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

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 Part 1 and Part 2, pharmacodynamic effects of SCH 727965 with an ex vivo lymphocyte stimulation assay of participant's peripheral blood lymphocytes.
timeFrame: Cycle 1
Secondary outcomes:
measure: In Part 3, area under the plasma concentration versus time curve and maximum concentration of SCH 727965 administered as a 2 hour intravenous infusion with or without aprepitant in participants with advanced malignancies.
timeFrame: Cycle 1 Days 1 and 2, and Cycle 2 Days 1 and 2
Other outcomes:
Locations:
Study officials:
References:
citation: Zhang D, Mita M, Shapiro GI, Poon J, Small K, Tzontcheva A, Kantesaria B, Zhu Y, Bannerji R, Statkevich P. Effect of aprepitant on the pharmacokinetics of the cyclin-dependent kinase inhibitor dinaciclib in patients with advanced malignancies. Cancer Chemother Pharmacol. 2012 Dec;70(6):891-8. doi: 10.1007/s00280-012-1967-y. Epub 2012 Oct 9.
citation: Mita MM, Mita AC, Moseley JL, Poon J, Small KA, Jou YM, Kirschmeier P, Zhang D, Zhu Y, Statkevich P, Sankhala KK, Sarantopoulos J, Cleary JM, Chirieac LR, Rodig SJ, Bannerji R, Shapiro GI. Phase 1 safety, pharmacokinetic and pharmacodynamic study of the cyclin-dependent kinase inhibitor dinaciclib administered every three weeks in patients with advanced malignancies. Br J Cancer. 2017 Oct 24;117(9):1258-1268. doi: 10.1038/bjc.2017.288. Epub 2017 Aug 31.