Phase 1
N=38
Relative Bioavailability of Pimasertib in Cancer Patients
Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT01992874 ↗Enrolled (actual)
38
Serious AEs
17.7%
Results posted
May 2016
Primary outcome: Primary: Maximum Observed Plasma Concentration (Cmax) — 254.6; 314.1 nanogram per milliliter (ng/mL)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Pimasertib Capsule (Part A) (Drug); Pimasertib Tablet (Part A) (Drug); Pimasertib Capsule (Part B and trial extension phase) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- EMD Serono
- Primary completion
- May 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) |
254.6; 314.1 | — |
| PRIMARY Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t) |
979.0; 1060.7 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf) |
1110.3; 1109.2 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) |
0.750; 0.517 | — |
| SECONDARY Apparent Terminal Half-life (t1/2) |
4.38; 4.47 | — |
| SECONDARY Apparent Total Body Clearance (CL/f) |
54.041; 54.092 | — |
| SECONDARY Apparent Volume of Distribution (Vz/f) |
346.454; 334.540 | — |
| SECONDARY Terminal Rate Constant (λz) |
0.16; 0.15 | — |
| SECONDARY Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation |
19; 20; 38; 1; 0; 19 | — |
| SECONDARY Part B: Number of Subjects Who Experienced Complete Response (CR) |
— | — |
| SECONDARY Part B: Number of Subjects Who Experienced Partial Response (PR) |
1 | — |
| SECONDARY Part B: Number of Subjects Who Experienced Stable Disease (SD) |
10 | — |
| SECONDARY Part B: Number of Subjects Who Experienced Progressive Disease (PD) |
15 | — |
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
Data sourced from ClinicalTrials.gov (NCT01992874). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.