NeoplasmsPhase 1NCT01992874
Relative Bioavailability of Pimasertib in Cancer Patients
A Phase 1 study testing Pimasertib Capsule (Part A), Pimasertib Tablet (Part A) and Pimasertib Capsule (Part B and trial extension phase) in people with Neoplasms, run by EMD Serono at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Neoplasms
- What is being tested?
- Pimasertib Capsule (Part A), Pimasertib Tablet (Part A) and Pimasertib Capsule (Part B and trial extension phase)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2013to 28 Feb 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Please Contact U.S. Medical Information Located in
Rockland, Massachusetts
About this study
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
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).
- Conditions
- Neoplasms
- Being tested
- Pimasertib Capsule (Part A), Pimasertib Tablet (Part A), Pimasertib Capsule (Part B and trial extension phase)
- Keywords
- Neoplasms, Pimasertib, Cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pimasertib Capsule (Part A)Drug
Also called AS703026, MSC1936369B
Pimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A.
Pimasertib Tablet (Part A)Drug
Also called AS703026, MSC1936369B
Pimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A.
Pimasertib Tablet (Part A)Drug
Also called AS703026, MSC1936369B
Pimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A.
Pimasertib Capsule (Part A)Drug
Also called AS703026, MSC1936369B
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
Also called AS703026, MSC1936369B
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.
| Study group | Role | What they receive |
|---|---|---|
| Pimasertib Capsule/Pimasertib Tablet | Experimental | Not described Receives: Drug: Pimasertib Capsule (Part A); Drug: Pimasertib Tablet (Part A); Drug: Pimasertib Capsule (Part B and trial extension phase) |
| Pimasertib Tablet/Pimasertib Capsule | Experimental | Not described Receives: Drug: Pimasertib Tablet (Part A); Drug: Pimasertib Capsule (Part A); Drug: Pimasertib Capsule (Part B and trial extension phase) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax) was calculated for Part A Pimasertib 60 mg Capsule and tablet.
Measured: 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.
Measured: 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 (11)
Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC0-inf)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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)
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.
Measured: 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)
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study start30 Nov 2013
- Primary completion31 May 2014
- Study completion28 Feb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01992874
- Sponsor's protocol ID
- 200066-013
- Status last verified
- Jul 2017
- First submitted
- 8 Nov 2013
- Last updated
- 15 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28289865
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01992874
- Acronym / sponsor ID
- 200066-013
- Conditions
- Neoplasms
- Keywords
- Neoplasms, Pimasertib, Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Study start
- 30 Nov 2013 (actual)
- Primary completion
- 31 May 2014 (actual)
- Study completion
- 28 Feb 2015 (actual)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Posted 11 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pimasertib Capsule/Pimasertib Tablet | Experimental | Drug: Pimasertib Capsule (Part A), Drug: Pimasertib Tablet (Part A), Drug: Pimasertib Capsule (Part B and trial extension phase) |
| Pimasertib Tablet/Pimasertib Capsule | Experimental | Drug: Pimasertib Tablet (Part A), Drug: Pimasertib Capsule (Part A), Drug: Pimasertib Capsule (Part B and trial extension phase) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pimasertib Capsule (Part A)Also: AS703026, MSC1936369BPimasertib capsule administration at a single dose of 60 milligram (mg) orally on Day 1 in Part A. | Drug | Pimasertib Capsule/Pimasertib Tablet |
| Pimasertib Tablet (Part A)Also: AS703026, MSC1936369BPimasertib tablet administration at a single dose of 60 mg orally on Day 3 in Part A. | Drug | Pimasertib Capsule/Pimasertib Tablet |
| Pimasertib Tablet (Part A)Also: AS703026, MSC1936369BPimasertib tablet administration at a single dose of 60 mg orally on Day 1 in Part A. | Drug | Pimasertib Tablet/Pimasertib Capsule |
| Pimasertib Capsule (Part A)Also: AS703026, MSC1936369BPimasertib capsule administration at a single dose of 60 mg orally on Day 3 in Part A. | Drug | Pimasertib Tablet/Pimasertib Capsule |
| Pimasertib Capsule (Part B and trial extension phase)Also: AS703026, MSC1936369BSubjects 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. | Drug | Pimasertib Capsule/Pimasertib Tablet, Pimasertib Tablet/Pimasertib Capsule |
Primary outcome
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.
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.
11 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)
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)
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
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)
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)
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)
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)
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28289865Mahadevan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pimasertib Capsule (Part A), Pimasertib Tablet (Part A) and Pimasertib Capsule (Part B and trial extension phase) in people with Neoplasms, run by EMD Serono at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01992874, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2017.