Gastroesophageal CancerPhase 2NCT03997448
Abemaciclib and Pembrolizumab in Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149
A Phase 2 study testing Pembrolizumab and Abemaciclib in people with Gastroesophageal Cancer and Adenocarcinoma, run by Nataliya Uboha at 4 sites in United States.
Trial summary
This study will test the combination of abemaciclib with pembrolizumab in patients with gastric, gastroesophageal junction, or esophageal adenocarcinoma that is metastatic or cannot be surgically removed, and who have progressed on, or were unable to tolerate, at least 2 earlier courses of treatment for their advanced… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastroesophageal Cancer, Adenocarcinoma
- What is being tested?
- Pembrolizumab and Abemaciclib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 4 sitesUnited States
- Study dates
- 26 Aug 2019to 30 Jan 2020
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed metastatic or locally advanced unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma.
- Be willing and able to provide written informed consent for the trial.
- Age >= 18 years at the time of consent.
- Prior treatment with at least two lines of systemic therapy for advanced disease. Patients who have received neoadjuvant or adjuvant therapy or definitive chemoradiation and had recurrence during or within 6 months of completion of all treatments may count adjuvant therapy as one chemotherapy line.
- Presence of measurable disease based on RECIST 1.1 as determined by local site investigator/radiology assessment.
- ECOG PS 0-1.
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- Patients must have discontinued all previous treatments for cancer (including cytotoxic chemotherapy, molecularly targeted therapy, radiotherapy, and investigational therapy).
- Patients who received chemotherapy must have recovered (CTCAE Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy. A washout period of at least 21 days is required between last systemic therapy dose and treatment initiation per protocol.
- A washout period of at least 14 days is required between end of radiotherapy and treatment initiation.
- The patient is able to swallow oral medications.
- Demonstrate adequate organ function as defined in the table in the protocol.
- Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 60 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method.
- Men who are not surgically sterile (vasectomy) must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms from the first dose of study drug through at least 60 days after the last dose of study drug. Total abstinence for the same time period is an acceptable alternative.
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
- Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB). NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
Who cannot join
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- History of prior therapy with CDK4 or CDK6 inhibitors or prior immune checkpoint inhibitors.
- Patients with known microsatellite instability will be excluded.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study PI.
- Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
- Symptomatic central nervous system metastasis. Screening of asymptomatic patients is not required for enrollment.
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- Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
- Known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include curatively treated basal cell and squamous cell carcinoma of the skin, curatively resected in situ cervical and/or breast cancers, in situ or intramucosal pharyngeal cancer, and Gleason 6 prostate cancer with PSA <10.
- Patients who have received a live vaccine within 30 days of planned start of pembrolizumab.
- Note: The killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines, and are not allowed.
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Active infection requiring systemic therapy.
- Patients who are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 60 days after the last dose of pembrolizumab or abemaciclib. (NOTE: breast milk cannot be stored for future use while the mother is being treated on study.)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
Univerisy of Iowa Hospital and Clinics
Iowa City, Iowa, 52242
University of Wisconsin
Madison, Wisconsin, 53705
Rutgers Cancer Institute of NewJjersey
New Brunswick, New Jersey, 08903
About this study
Official title: Phase II Study of the Combination of Abemaciclib and Pembrolizumab in Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149
This study will test the combination of abemaciclib with pembrolizumab in patients with gastric, gastroesophageal junction, or esophageal adenocarcinoma that is metastatic or cannot be surgically removed, and who have progressed on, or were unable to tolerate, at least 2 earlier courses of treatment for their advanced disease.
Read the detailed description
This is a Phase II non-randomized, single arm, open label study of abemaciclib in combination with pembrolizumab in patients with unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma who have received at least two lines of prior therapy. Treatment will be administered in 21-day cycles. Pembrolizumab will be administered intravenously (IV) at a dose of 200 mg on day 1 of each cycle. Abemaciclib will be taken orally twice a day on each day of the cycle, 150 mg per dose. Treatment will continue until disease progression or development of unacceptable toxicities.
- Conditions
- Gastroesophageal Cancer, Adenocarcinoma
- Being tested
- Pembrolizumab, Abemaciclib
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab 200mg IV
AbemaciclibDrug
Abemiciclib 150mg PO
| Study group | Role | What they receive |
|---|---|---|
| Abemaciclib and Pembrolizumab | Experimental | Abemaciclib 150mg days 1-21, and Pembrolizumab 200mg IV, Day 1 Receives: Drug: Pembrolizumab; Drug: Abemaciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival(PFS)
Progression free survival is defined as the time of treatment initiation until the criteria for disease progression per RECIST1.1 are met or until the date of a death event (any cause). Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progressions).
Measured: From C1D1 until death or up to a maximum of 5 months
Secondary outcomes (6)
PFS Per irRECIST
A measurement from the date of the start of treatment until the criteria for disease progression is met as defined by irRECIST or death occurs.Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of new lesions is not considered PD but are to be included in the sum diameters. Confirmation required at least 4 weeks after the first irPD assessment provided the patient is considered clinically stable.
Measured: From C1D1 until death or up to a maximum of 5 months
Progression-Free Survival Rate at 6 Months Per RECIST 1.1 and irRECIST
6 months PFS rate is defined as the proportion of subjects who have experienced no progressive disease or death at a 6 month time point from time of treatment initiation using RECIST and irRECIST criteria. Progressive disease per RECIST 1.1 and irRECIST is defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Per RECIST 1.1, the appearance of one or more new lesions is also considered progression. Per irRECIST, confirmation is required at least 4 weeks after the first irPD assessment provided the patient is considered clinically stable.
Measured: From C1D1 until death or up to a maximum of 6 months
Objective Response Rate
Objective response rate is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1 and irRECIST criteria, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR/irCR), Disappearance of all target lesions; Partial Response (PR/irPR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: From C1D1 until death or up to a maximum of 5 months
Disease Control Rate
The disease control rate is the proportion of all subjects with stable disease (SD) for 16 weeks, or partial response (PR), or complete response (CR) according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment). RECIST and irRECIST criteria will be applied. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to <10 mm. Stable disease is defined neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: From C1D1 until death or up to a maximum of 5 months
Overall Survival
Overall survival is defined by the duration of subject's survival from the start of treatment till death from any cause or off- study.
Measured: From C1D1 until death or up to a maximum of 5 months
Number of Participants With Specified Safety and Tolerability of Abemaciclib in Combination With Pembrolizumab
Safety and tolerability of abemaciclib in combination with pembrolizumab in patients with advanced, unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Measured: From C1D1 until death or up to a maximum of 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2019
- Study start26 Aug 2019
- Primary completion30 Jan 2020
- Study completion30 Jan 2020
Why it stopped: Funder decision
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.
- Other trials for Gastroesophageal CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nataliya Uboha
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor-investigator, Nataliya Uboha, Big Ten Cancer Research Consortium
- Investigators
- Nataliya Uboha, MD, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03997448
- Sponsor's protocol ID
- BTCRC-GI18-149
- Status last verified
- Feb 2024
- First submitted
- 24 Jun 2019
- Last updated
- 20 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Combination of Abemaciclib and Pembrolizumab in Locally Advanced Unresectable or Metastatic Gastroesophageal Adenocarcinoma: Big Ten Cancer Research Consortium BTCRC-GI18-149
- ClinicalTrials.gov ID
- NCT03997448
- Acronym / sponsor ID
- BTCRC-GI18-149
- Conditions
- Gastroesophageal Cancer, Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funder decision
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Nataliya UbohaUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 26 Aug 2019 (actual)
- Primary completion
- 30 Jan 2020 (actual)
- Study completion
- 30 Jan 2020 (actual)
- First posted
- 25 Jun 2019 (actual)
- Results
- Posted 20 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the combination of abemaciclib with pembrolizumab in patients with gastric, gastroesophageal junction, or esophageal adenocarcinoma that is metastatic or cannot be surgically removed, and who have progressed on, or were unable to tolerate, at least 2 earlier courses of treatment for their advanced disease.
Detailed description
This is a Phase II non-randomized, single arm, open label study of abemaciclib in combination with pembrolizumab in patients with unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma who have received at least two lines of prior therapy. Treatment will be administered in 21-day cycles. Pembrolizumab will be administered intravenously (IV) at a dose of 200 mg on day 1 of each cycle. Abemaciclib will be taken orally twice a day on each day of the cycle, 150 mg per dose. Treatment will continue until disease progression or development of unacceptable toxicities.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Abemaciclib and Pembrolizumab | Experimental | Drug: Pembrolizumab, Drug: AbemaciclibAbemaciclib 150mg days 1-21, and Pembrolizumab 200mg IV, Day 1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with histologically confirmed metastatic or locally advanced unresectable gastric, gastroesophageal junction or esophageal adenocarcinoma.
- Be willing and able to provide written informed consent for the trial.
- Age >= 18 years at the time of consent.
- Prior treatment with at least two lines of systemic therapy for advanced disease. Patients who have received neoadjuvant or adjuvant therapy or definitive chemoradiation and had recurrence during or within 6 months of completion of all treatments may count adjuvant therapy as one chemotherapy line.
- Presence of measurable disease based on RECIST 1.1 as determined by local site investigator/radiology assessment.
Key exclusion criteria (13 listed)
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- History of prior therapy with CDK4 or CDK6 inhibitors or prior immune checkpoint inhibitors.
- Patients with known microsatellite instability will be excluded.
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the study PI.
- Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
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 |
|---|---|---|
| PembrolizumabPembrolizumab 200mg IV | Drug | Abemaciclib and Pembrolizumab |
| AbemaciclibAbemiciclib 150mg PO | Drug | Abemaciclib and Pembrolizumab |
Primary outcome
Progression-Free Survival(PFS)
Time frame: From C1D1 until death or up to a maximum of 5 months
Progression free survival is defined as the time of treatment initiation until the criteria for disease progression per RECIST1.1 are met or until the date of a death event (any cause). Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progressions).
6 secondary outcomes
PFS Per irRECIST
Time frame: From C1D1 until death or up to a maximum of 5 months
Progression-Free Survival Rate at 6 Months Per RECIST 1.1 and irRECIST
Time frame: From C1D1 until death or up to a maximum of 6 months
Objective Response Rate
Time frame: From C1D1 until death or up to a maximum of 5 months
Disease Control Rate
Time frame: From C1D1 until death or up to a maximum of 5 months
Overall Survival
Time frame: From C1D1 until death or up to a maximum of 5 months
Number of Participants With Specified Safety and Tolerability of Abemaciclib in Combination With Pembrolizumab
Time frame: From C1D1 until death or up to a maximum of 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Nataliya Uboha, MD, PhD principal investigator
University of Wisconsin, Madison
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Abemaciclib in people with Gastroesophageal Cancer and Adenocarcinoma, run by Nataliya Uboha at 4 sites 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 16 inclusion and 13 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: stopped early, as of the sponsor's last update on 20 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 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?
Yes. Results are posted in the registry (first posted 20 Feb 2024). 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?
Progression-Free Survival(PFS) (time frame: From C1D1 until death or up to a maximum of 5 months). 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 20 Feb 2024.