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Relative Bioavailability of Pimasertib in Cancer Patients

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ClinicalTrials.gov Identifier: NCT01992874
Recruitment Status : Completed
First Posted : November 25, 2013
Results First Posted : May 11, 2016
Last Update Posted : August 15, 2017
Sponsor:
Information provided by (Responsible Party):
EMD Serono

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).

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Pimasertib Capsule (Part A) Drug: Pimasertib Tablet (Part A) Drug: Pimasertib Capsule (Part B and trial extension phase) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 30, 2013
Actual Primary Completion Date : May 31, 2014
Actual Study Completion Date : February 28, 2015

Arm Intervention/treatment
Experimental: Pimasertib Capsule/Pimasertib Tablet Drug: Pimasertib Capsule (Part A)
Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.
Other Names:
  • AS703026
  • MSC1936369B

Drug: Pimasertib Tablet (Part A)
Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.
Other Names:
  • AS703026
  • MSC1936369B

Drug: Pimasertib Capsule (Part B and trial extension phase)
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.
Other Names:
  • AS703026
  • MSC1936369B

Experimental: Pimasertib Tablet/Pimasertib Capsule Drug: Pimasertib Tablet (Part A)
Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.
Other Names:
  • AS703026
  • MSC1936369B

Drug: Pimasertib Capsule (Part A)
Pimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A.
Other Names:
  • AS703026
  • MSC1936369B

Drug: Pimasertib Capsule (Part B and trial extension phase)
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.
Other Names:
  • AS703026
  • MSC1936369B




Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) [ 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 ]
    Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.

  2. Area Under the Plasma Concentration-time Curve From Zero to the Last Quantifiable Concentration (AUC 0-t) [ 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 time zero to the last sampling time (AUC0-t) at which the concentration was at or above the lower limit of quantification.


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  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 ]
  4. Apparent Total Body Clearance (CL/f) [ 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 ]
    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.

  5. Apparent Volume of Distribution (Vz/f) [ 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 ]
    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.

  6. 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 ]
  7. Number of Subjects With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation [ 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 ]
    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.

  8. Part B: Number of Subjects Who Experienced Complete Response (CR) [ 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 ]
    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).

  9. Part B: Number of Subjects Who Experienced Partial Response (PR) [ 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 ]
    PR as per RECIST v1.1 defined as 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters.

  10. Part B: Number of Subjects Who Experienced Stable Disease (SD) [ 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 ]
    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.

  11. Part B: Number of Subjects Who Experienced Progressive Disease (PD) [ 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 ]
    PD as per RECIST v1.1 defined as 20% increase in sum of diameters of target lesions; the appearance of >=1 new lesions.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01992874


Locations
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United States, Massachusetts
Please Contact U.S. Medical Information Located in
Rockland, Massachusetts, United States
Sponsors and Collaborators
EMD Serono
Investigators
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Study Director: Medical Responsible EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany

Publications of Results:
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Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01992874     History of Changes
Other Study ID Numbers: 200066-013
First Posted: November 25, 2013    Key Record Dates
Results First Posted: May 11, 2016
Last Update Posted: August 15, 2017
Last Verified: July 2017
Keywords provided by EMD Serono:
Neoplasms
Pimasertib
Cancer
Additional relevant MeSH terms:
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Neoplasms
Niacinamide
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs