Phase 1 Every-3-Week Dosing of SCH 727965 in Patients With Advanced Cancer (Study P04630)

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00871910
• Other study ID #: P04630
• Status: Completed
• Phase: Phase 1
• First received: March 26, 2009
• Last updated: October 20, 2017
• Start date: October 11, 2006
• Est. completion date: February 22, 2010

Study information

• Verified date: October 2017
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: February 22, 2010
• Est. primary completion date: February 22, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Solid Tumors

Intervention

Drug:
• SCH 727965
SCH 727965 2 hour IV infusion on Day 1 of each 3 week cycle, administered in dose-escalating cohorts (Part 1 of the trial)
• SCH 727965
SCH 727965 8 hour IV infusion on Day 1 of each 3 week cycle,in dose-escalating cohorts
• SCH 727965
SCH 727965 24 hour IV infusion on Day 1 of each 3 week cycle, in dose-escalating cohorts
• SCH 727965
SCH 727965 29.6 mg/m2 2 hour IV infusion on Day 1 of each 3 week cycle
• Aprepitant
Oral aprepitant in Cycle 1 or Cycle 2, depending on the study arm: 125 mg 1 hour prior to the SCH 727965 infusion on Day 1, and 80 mg on Days 2 and 3.
• Ondansetron
Ondansetron 32 mg IV 30 minutes prior to the SCH 727965 infusion on Day 1 of Cycles 1 and 2.
• Dexamethasone
Oral dexamethasone in Cycles 1 and 2: 12 mg 30 minutes prior to the SCH 727965 infusion on Day 1, and 8 mg in the morning on Days 2, 3, and 4.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (2)

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 c — View 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 Chem — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity		End of trial
Primary	In Part 1 and Part 2, pharmacodynamic effects of SCH 727965 with an ex vivo lymphocyte stimulation assay of participant's peripheral blood lymphocytes.		Cycle 1
Secondary	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.		Cycle 1 Days 1 and 2, and Cycle 2 Days 1 and 2