Clinical trial NCT01992874: Relative Bioavailability of Pimasertib in Cancer Patients
Official title: A Multi-Center, Open-Label, Single 60 mg Dose, Two Period, Two Sequence Cross-Over Trial to Investigate the Relative Bioavailability of Two Solid Oral Pimasertib Formulations in Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Neoplasms
Pimasertib
Cancer
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, multi-center, open-label, single-dose, 2 period, 2 sequence cross-over trial to investigate the relative bioavailability of 2 solid oral pimasertib formulations in cancer subjects (Part A), followed by open-label pimasertib administration (Part B and trial extension phase).


Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed solid tumors, either refractory to standard therapy or for which no effective standard therapy is available, with a measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* An Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to (\<=) 1
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Disease conditions or concomitant medication that may significantly influence the conduct of the trial or an abnormal electrocardiogram (ECG) or blood pressure at Screening as defined in the protocol
* Treatment with strong inhibitors or inducers of cytochrome P450 2C19 (CYP2C19) and CYP3A4 including fruit juices or beverages containing these substances
* History of prior mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) kinase (MEK) inhibitor exposure (including, pimasertib) or progression of disease on MEK inhibitors
* Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of RVO
* Life expectancy of less than 12 weeks
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Apparent Terminal Half-life (t1/2)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Apparent Total Body Clearance (CL/f)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Apparent Volume of Distribution (Vz/f)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Terminal Rate Constant (λz)
timeFrame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 8, and 24 hours post-dose on Day 1 and 3
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
timeFrame: From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months
measure: Part B: Number of Subjects Who Experienced Complete Response (CR)
timeFrame: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
measure: Part B: Number of Subjects Who Experienced Partial Response (PR)
timeFrame: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
measure: Part B: Number of Subjects Who Experienced Stable Disease (SD)
timeFrame: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
measure: Part B: Number of Subjects Who Experienced Progressive Disease (PD)
timeFrame: Screening to Day 1 of each cycle (21 day in each cycle) until disease progression, intolerable toxicity, withdrawal of consent or death; assessed up to 14 Months
Other outcomes:
Locations:
city: Rockland
country: United States
facility: Please Contact U.S. Medical Information Located in
state: Massachusetts
Study officials:
affiliation: EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Mahadevan D, Mita M, Richards D, McClay E, Heist RS, Kumar A, Sundararajan S, Naing A. Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients. Cancer Chemother Pharmacol. 2017 Apr;79(4):681-688. doi: 10.1007/s00280-017-3258-0. Epub 2017 Mar 13.