Relative Bioavailability of Pimasertib in Cancer Patients

Phase 1CompletedNCT01992874

EMD Serono38 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neoplasms

Interventions

Pimasertib Capsule (Part A)DRUG

Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.

Pimasertib Tablet (Part A)DRUG

Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.

Pimasertib Tablet (Part A)DRUG

Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (1)

Please Contact U.S. Medical Information Located in

Rockland, Massachusetts, United States

Outcomes

Primary Outcomes

Maximum Observed Plasma Concentration (Cmax)

Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.

Time frame: 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

Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t)

Area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification.

Time frame: 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

Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf)

Time frame: 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

Time to Reach Maximum Observed Plasma Concentration (Tmax)

Time frame: 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

Apparent Terminal Half-life (t1/2)

Time frame: 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

Apparent Total Body Clearance (CL/f)

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

Time frame: 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

Apparent Volume of Distribution (Vz/f)

Data from ClinicalTrials.gov

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Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A.

Pimasertib Capsule (Part B and trial extension phase)DRUG

Subjects completing Part A to receive pimasertib capsule at a dose of 60 mg orally twice daily in cycles of 21 days each in Part B and trial extension phase until disease progression, intolerable toxicity, subject withdrawal, loss to follow-up or death.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

Time frame: 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

Terminal Rate Constant (λz)

Time frame: 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

Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug administration until 30 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pre treatment state.

Time frame: From the first dose of study drug administration until 30 days after the last dose of study drug administration, assessed up to 14 Months

Part B: Number of Subjects Who Experienced Complete Response (CR)

CR as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 defined as disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to less than (\<)10 millimeter (mm).

Time frame: 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

Part B: Number of Subjects Who Experienced Partial Response (PR)

PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters.

Time frame: 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

Part B: Number of Subjects Who Experienced Stable Disease (SD)

SD as per RECIST v1.1 defined as neither shrinkage to qualify for PR nor increase to qualify for progressive disease (PD) taking the smallest sum diameters on study as reference. PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; PD = 20% increase in sum of diameters of target lesions; the appearance of \>=1 new lesions.

Time frame: 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

Part B: Number of Subjects Who Experienced Progressive Disease (PD)

PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of \>=1 new lesions.

Time frame: 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