TumorsPhase 1/2NCT04594005
CDK4/6 Tumor, Abemaciclib, Paclitaxel
A Phase 1/2 study testing abemaciclib+paclitaxel in people with Tumors, run by Yonsei University at 1 site in South Korea.
Trial summary
Cyclin D-dependent kinases (CDKs) are often activated in human cancer owing to various genetic and epigenetic events. This affects regulatory pathways, and it results in uncontrolled proliferation due to loss of checkpoint integrity. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Tumors
- What is being tested?
- abemaciclib+paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSouth Korea
- Study dates
- 25 Feb 2021to 10 Aug 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed locally advanced or metastatic solid tumors, for which standard therapy proven to provide clinical benefit no longer
- CDK4/6 activated tumors on next-generation sequencing or FISH (fluorescence in situ hybridization) analyses
- CCND1, 2, or 3 high-level amplification, CCND1 mutation, or a CCND1 splice variant expected to lead to nuclear retention of cyclin D1 protein
- CDK4 or CDK6 high-level amplification
- ECOG performance status of 0 to 1
- ≥ 19 years of age
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- Subjects with measurable or evaluable disease ⑥ Subjects who meet the following criteria: - Absolute neutrophil count (ANC) ≥ 1500 /µL (*ANC = Neutrophil segs ＋ Neutrophil bands) - Platelet count ≥ 75,000/ µL - Serum creatinine < 1.5 x upper limit of normal (ULN)
- AST (SGOT) and ALT (SGPT) < 3 x upper limit of normal (ULN) (If there is Liver Metastasis < 5 x upper limit of normal (ULN))
- Total bilirubin < 1.5 x upper limit of normal (ULN)
- Provision of written informed consent prior to any study procedure
Who cannot join
- Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy.
- Any previous chemotherapy or immunotherapy within 2 weeks or at least 3-5 half-lives for previous chemo/immunotherapy whichever is longer.
- Any major operation or irradiation within 2 weeks of baseline disease assessment
- Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
- Previously abemaciclib-exposed patients
- ⑥ Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
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- ⑦ Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma, thyroid cancer or cervical cancer in situ.
- ⑧ Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension)
- ⑨ Active infection including hepatitis B, hepatitis C
- ⑩ Pregnant or lactating female
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Multi-center Phase IB/II Study of Abemaciclib With Paclitaxel for CDK4/6 Pathway Activated Tumors
Cyclin D-dependent kinases (CDKs) are often activated in human cancer owing to various genetic and epigenetic events. This affects regulatory pathways, and it results in uncontrolled proliferation due to loss of checkpoint integrity. Most tumors show increased activity of CDKs, and this permits escape from senescence during the evolution of malignancy.
Among them, cyclin D-CDK4/6-INK4 pathway alterations accelerate G1 progression which provides proliferative and survival advantage to cancer. Therefore, preclinical data demonstrated inhibition of cyclin D-dependent kinase activity have therapeutic benefit. CDK4/6 controls entry into cell cycle progression by regulating Retinoblastoma protein (Rb). The majority of human cancers are known to retain wild-type Rb. In addition, CDK4 amplification and mutations also noted in several tumors. In Rb retained tumors, CDK 4/6 inhibitors reduced Rb phosphorylation and induced G1 arrest. In previous study, CDK4/6 inhibitor showed antitumor activities in Rb-positive breast and colon cancer cell lines. Rapid tumor regression was also noticed in mouse xenograft model. In CDK4 amplified sarcoma cell lines, knockdown of CDK4 inhibited cancer cell proliferation.
Cyclin D1 acts with CDK4 and CDK6 to phosphorylate Rb and promote cell-cycle progression, and CDK4/6 inhibitor might be effective for the patients with CCND1/2/3 amplification/mutation or CDK 4/6 amplification. Therefore, basket trial (NCT03310879) is ongoing for the patients with genomic alterations in CCND1, CDKN2A, or CDK4. Amplification/mutation of CCND1/2/3 and CDK4/6 occurs in approximately 15-30% of various solid tumors; sarcoma, GBM, melanoma, gem cell tumor, and gynecologic tumors Regarding the more potent synergistic effect, paclitaxel demonstrated a rationale for promising combination partner with CDK 4/6 inhibitors. In non-small cell lung cancer cell lines, synergistic anti-tumor activities were reported with paclitaxel combination. Corollary, we planned to conduct the phase Ib/II trial of abemaciclib and paclitaxel combination in CDK4/6 pathway activated tumors as one subgroup of multi-arms in ongoing basket trial.
- Conditions
- Tumors
- Being tested
- abemaciclib+paclitaxel
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
abemaciclib+paclitaxelDrug
Phase 1b: About 3-6 patients enrollment is expected at dose level 1, -1 and -2. Dose reduction will be preceded with 3 patients/cohort until the first DLT with 4 weeks' observation. The recommend phase 2 dose (RP2D) will be defined.
level1: abemaciclib 100mg bid, D1-28 / paclitaxel 80mg/m2, IV. D1, 8, 15 Q 4 weeks level-1: abemaciclib 100mg bid, D1-28 / paclitaxel 70mg/m2, IV. D1, 8, 15 Q 4 weeks level-2: abemaciclib 50mg bid, D1-28 / paclitaxel 70mg/m2, IV. D1, 8, 15 Q 4 weeks
Phase2: At the RP2D dose level in phase I part, we will expand phase 2 study.
| Study group | Role | What they receive |
|---|---|---|
| abemaciclib+paclitaxel | Experimental | Not described Receives: Drug: abemaciclib+paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate
Measured: 8 weeks
recommend phase 2 dose
to find the recommend phase 2 dose
Measured: during 28 days after 1st dose
Secondary outcomes (3)
adverse event
Measured: 1 week
disease control rate
Measured: 8 weeks
progression free survival
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2020
- Study start25 Feb 2021
- Primary completion16 Jul 2024
- Study completion10 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TumorsStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hyo Song Kim, Yonsei University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04594005
- Sponsor's protocol ID
- 4-2020-0091
- Status last verified
- Dec 2024
- First submitted
- 14 Oct 2020
- Last updated
- 18 Dec 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center Phase IB/II Study of Abemaciclib With Paclitaxel for CDK4/6 Pathway Activated Tumors
- ClinicalTrials.gov ID
- NCT04594005
- Acronym / sponsor ID
- 4-2020-0091
- Conditions
- Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 16 Jul 2024 (actual)
- Study completion
- 10 Aug 2024 (actual)
- First posted
- 20 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cyclin D-dependent kinases (CDKs) are often activated in human cancer owing to various genetic and epigenetic events. This affects regulatory pathways, and it results in uncontrolled proliferation due to loss of checkpoint integrity. Most tumors show increased activity of CDKs, and this permits escape from senescence during the evolution of malignancy.
Among them, cyclin D-CDK4/6-INK4 pathway alterations accelerate G1 progression which provides proliferative and survival advantage to cancer. Therefore, preclinical data demonstrated inhibition of cyclin D-dependent kinase activity have therapeutic benefit. CDK4/6 controls entry into cell cycle progression by regulating Retinoblastoma protein (Rb). The majority of human cancers are known to retain wild-type Rb. In addition, CDK4 amplification and mutations also noted in several tumors. In Rb retained tumors, CDK 4/6 inhibitors reduced Rb phosphorylation and induced G1 arrest. In previous study, CDK4/6 inhibitor showed antitumor activities in Rb-positive breast and colon cancer cell lines. Rapid tumor regression was also noticed in mouse xenograft model. In CDK4 amplified sarcoma cell lines, knockdown of CDK4 inhibited cancer cell proliferation.
Cyclin D1 acts with CDK4 and CDK6 to phosphorylate Rb and promote cell-cycle progression, and CDK4/6 inhibitor might be effective for the patients with CCND1/2/3 amplification/mutation or CDK 4/6 amplification. Therefore, basket trial (NCT03310879) is ongoing for the patients with genomic alterations in CCND1, CDKN2A, or CDK4. Amplification/mutation of CCND1/2/3 and CDK4/6 occurs in approximately 15-30% of various solid tumors; sarcoma, GBM, melanoma, gem cell tumor, and gynecologic tumors Regarding the more potent synergistic effect, paclitaxel demonstrated a rationale for promising combination partner with CDK 4/6 inhibitors. In non-small cell lung cancer cell lines, synergistic anti-tumor activities were reported with paclitaxel combination. Corollary, we planned to conduct the phase Ib/II trial of abemaciclib and paclitaxel combination in CDK4/6 pathway activated tumors as one subgroup of multi-arms in ongoing basket trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| abemaciclib+paclitaxel | Experimental | Drug: abemaciclib+paclitaxel |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically or cytologically confirmed locally advanced or metastatic solid tumors, for which standard therapy proven to provide clinical benefit no longer
Key exclusion criteria (10 listed)
- Any unresolved chronic toxicity greater than CTC grade 2 from previous anticancer therapy.
- ⑥ Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
- ⑦ Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma, thyroid cancer or cervical cancer in situ.
- ⑧ Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome, 2° or more AV Block and uncontrolled hypertension)
- ⑨ Active infection including hepatitis B, hepatitis C
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 |
|---|---|---|
| abemaciclib+paclitaxelPhase 1b: About 3-6 patients enrollment is expected at dose level 1, -1 and -2. Dose reduction will be preceded with 3 patients/cohort until the first DLT with 4 weeks' observation. The recommend phase 2 dose (RP2D) will be defined. level1: abemaciclib 100mg bid, D1-28 / paclitaxel 80mg/m2, IV. D1, 8, 15 Q 4 weeks level-1: abemaciclib 100mg bid, D1-28 / paclitaxel 70mg/m2, IV. D1, 8, 15 Q 4 weeks level-2: abemaciclib 50mg bid, D1-28 / paclitaxel 70mg/m2, IV. D1, 8, 15 Q 4 weeks Phase2: At the RP2D dose level in phase I part, we will expand phase 2 study. | Drug | abemaciclib+paclitaxel |
Primary outcome
overall response rate
Time frame: 8 weeks
recommend phase 2 dose
Time frame: during 28 days after 1st dose
to find the recommend phase 2 dose
3 secondary outcomes
adverse event
Time frame: 1 week
disease control rate
Time frame: 8 weeks
progression free survival
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2024.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing abemaciclib+paclitaxel in people with Tumors, run by Yonsei University at 1 site in South Korea.
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 10 inclusion and 10 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 18 Dec 2024. 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 South Korea. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
overall response rate (time frame: 8 weeks). 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?
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 18 Dec 2024.