Solid Tumors for Phase IbPhase 1NCT02703571
Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
A Phase 1 study testing ribociclib and Trametinib in people with Solid Tumors for Phase Ib and Pancreatic Cancer for Phase II, run by Novartis Pharmaceuticals at 15 sites in 7 countries.
Trial summary
Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors for Phase Ib, Pancreatic Cancer for Phase II, Colorectal Cancer for Phase II
- What is being tested?
- ribociclib and Trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 15 sitesin 7 countries
- Study dates
- 29 Jun 2016to 24 Sep 2019
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent must
- Patient has histologically and/or cytologically confirmed malignancies:
- Phase I:
- Patients with advanced or metastatic solid tumors who have failed at least one prior line of systemic antineoplastic therapy in the advanced setting without a standard of care treatment option available;
- Phase II:
- Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic antineoplastic therapies in the advanced setting
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- Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic antineoplastic therapies in the advanced setting without a standard of care treatment option available. Testing for KRAS mutation in patients with CRC using locally approved diagnostic kit will be used for eligibility.
- Phase II only: patient must have measurable disease
- Patient has an ECOG performance status 0 or 1.
- Patient has adequate bone marrow and organ function
- Patient must have specified laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication on Cycle 1 Day 1:
- Standard 12-lead ECG values defined
Who cannot join
- Phase II only:
- Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
- Phase I and Phase II:
- Patient with a known hypersensitivity to the study drugs or any of the excipients of ribociclib or trametinib.
- Patient is concurrently using other anti-cancer therapy.
- Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to Cycle 1 Day 1
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- Patient has received local therapy to liver ≤ 3 months of C1D1
- History of liver disease as follow:
- Cirrhosis
- Autoimmune hepatitis
- Active viral hepatitis
- Portal hypertension
- Drug induced liver steatosis
- Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1
- Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for doxorubicin or 900 mg/m2 or more for epirubicin.
- Patient is currently receiving warfarin or other coumadin derived anti-coagulant
- Patient has a history of deep venin thrombosis or pulmonary embolism within 6 months of screening.
- Patient has a concurrent malignancy or malignancy within 3 years prior to Cycle 1 Day 1, with the exception of adequately treated basal or squamous cell carcinoma or curatively resected cervical cancer.
- Patients with central nervous system (CNS) involvement
- Patient has impairment of GI function or GI disease that may significantly alter the absorption of the study drugs
- History of interstitial lung disease or pneumonitis.
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
- Patient is currently receiving any strong inducers or inhibitors of CYP3A4/5 and/or Substances that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 and cannot be discontinued 7 days prior to Cycle 1 Day 1:
- Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
- History of retinal vein occlusion (RVO)
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
15 sites in 7 countries.
15 sites in 7 countries
United States6 sites
Dana Farber Cancer Center
Boston, Massachusetts, 02215
City of Hope National Medical Center
Duarte, California, 91010
Highlands Oncology Group
Fayetteville, Arkansas, 72703
UT MD Anderson Cancer Center
Houston, Texas, 77030
University of Miami Sylvester Comp Cancer Ctr
Miami, Florida, 33136
Yale University School of Medicine
New Haven, Connecticut, 06520
Canada2 sites
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Vancouver, British Columbia, V5Z 4E6
Germany2 sites
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Ulm, 89081
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1066 CX
Novartis Investigative Site
Utrecht, 3584 CX
About this study
Official title: A Phase I/II Study of Safety and Efficacy of Ribociclib (LEE011) in Combination With Trametinib (TMT212) in Patients With Metastatic or Advanced Solid Tumors
Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.
Read the detailed description
Upon careful review of all available efficacy and safety data from the study phase Ib part, Novartis decided to not start the study phase II part.
This decision was in no means triggered by an unfavorable safety profile of the combination. The observed safety profile of the combination represents contributions of the individual safety profile of trametinib and ribociclib.
No new safety signals were observed.
The study was closed early in line with protocol Section 4.4.
- Being tested
- ribociclib, Trametinib
- Keywords
- Trametinib, Ribociclib, LEE011, TMT212, advanced solid tumors, pancreatic cancer, KRAS-mutant colorectal cancer, colorectal cancer, advanced pancreatic cancer, metastatic pancreatic cancer
- Medical subject headings
- Pancreatic Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ribociclibDrug
Also called LEE011
Combination treatment with LEE and TMT
TrametinibDrug
Also called TMT212
Combination treatment with LEE and TMT
| Study group | Role | What they receive |
|---|---|---|
| Advanced or metastatic solid tumors | Experimental | Patients in the Phase I portion of the study who have advanced or metastatic solid tumors Receives: Drug: ribociclib; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities (DLTs)
Phase Ib part:
The primary variable is the incidence of DLTs during the first 21 days of therapy. Estimation of the MTD of the combination treatment will be based upon the estimation of the probability of DLT during the first 21 days of therapy for patients in the DDS.
Measured: 21-day cycle one of treatment
Objective Response Rate (ORR)
Phase II part:
The primary variable used to evaluate the efficacy of the ribociclib and trametinib combination is the ORR, defined as the proportion of patients with a best overall confirmed CR or PR, as assessed per RECIST 1.1 by investigator assessment.
Measured: Until progression of disease up to 1 year
Secondary outcomes (6)
Duration of response (DOR)
Phase II part:
Among patients with a confirmed response (PR or CR) per RECIST 1.1, DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause. The distribution function of DOR will be estimated using the Kaplan-Meier method. The median DOR along with 95% CI will be presented by treatment arm.
Measured: Until progression of disease up to 1 year
Time to response
Phase II part:
Time to overall response of CR or PR (TTR) is defined as the time from start of study drug to first documented response (CR or PR, which must be confirmed subsequently) for patients with a confirmed CR or PR. TTR will be summarized by treatment arm, using descriptive statistics.
Measured: Until progression of disease up to 1 year
Disease control rate
Phase II part:
Disease control rate (DCR) is defined as the proportion of patients with best overall response of CR, PR, or SD per RECIST 1.1. DCR will be estimated and the binomial exact 95% CI will be provided by arm.
Measured: Until progression of disease up to 1 year
Progression disease rate
Phase Ib part:
Progression disease rate defined as the proportion of patients with a progression disease as assessed per RECIST 1.1 by investigator assessment.
Measured: Until progression of disease up to 1 year
Progression free survival
Phase Ib and phase II parts:
Progression-free survival (PFS) is defined as the time from the date of the first dose of study drug to the date of first documented disease progression per RECIST 1.1 or death due to any cause.
Measured: Until progression of disease up to 1 year
overall survival
Phase Ib and phase II parts:
Overall survival (OS) is defined as the time from the date of first dose of study drug to the date of death due to any cause.
Measured: Until death up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2016 (estimated)
- Study start29 Jun 2016
- Primary completion24 Sep 2019
- Study completion24 Sep 2019
Why it stopped: Company decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumors for Phase IbStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single group for phase 1b parallel group for phase 2
- Masking
- None (open label)
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02703571
- Sponsor's protocol ID
- CTMT212X2106
- Other IDs
- 2015-005019-34, 2015
- Status last verified
- Sep 2020
- First submitted
- 4 Mar 2016
- Last updated
- 21 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Safety and Efficacy of Ribociclib (LEE011) in Combination With Trametinib (TMT212) in Patients With Metastatic or Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02703571
- Acronym / sponsor ID
- CTMT212X2106
- Keywords
- Trametinib, Ribociclib, LEE011, TMT212, advanced solid tumors, pancreatic cancer, KRAS-mutant colorectal cancer, colorectal cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 29 Jun 2016 (actual)
- Primary completion
- 24 Sep 2019 (actual)
- Study completion
- 24 Sep 2019 (actual)
- First posted
- 9 Mar 2016 (estimated)
- 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.
Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.
Detailed description
Upon careful review of all available efficacy and safety data from the study phase Ib part, Novartis decided to not start the study phase II part.
This decision was in no means triggered by an unfavorable safety profile of the combination. The observed safety profile of the combination represents contributions of the individual safety profile of trametinib and ribociclib.
No new safety signals were observed.
The study was closed early in line with protocol Section 4.4.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single group for phase 1b parallel group for phase 2
| Arm | Type | Receives |
|---|---|---|
| Advanced or metastatic solid tumors | Experimental | Drug: ribociclib, Drug: TrametinibPatients in the Phase I portion of the study who have advanced or metastatic solid tumors |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent must
- Patient has histologically and/or cytologically confirmed malignancies:
- Patients with advanced or metastatic solid tumors who have failed at least one prior line of systemic antineoplastic therapy in the advanced setting without a standard of care treatment option available;
- Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic antineoplastic therapies in the advanced setting
- Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic antineoplastic therapies in the advanced setting without a standard of care treatment option available. Testing for KRAS mutation in patients with CRC using locally approved diagnostic kit will be used for eligibility.
Key exclusion criteria (26 listed)
- Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
- Patient with a known hypersensitivity to the study drugs or any of the excipients of ribociclib or trametinib.
- Patient is concurrently using other anti-cancer therapy.
- Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to Cycle 1 Day 1
- Patient has received local therapy to liver ≤ 3 months of C1D1
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 |
|---|---|---|
| ribociclibAlso: LEE011Combination treatment with LEE and TMT | Drug | Advanced or metastatic solid tumors |
| TrametinibAlso: TMT212Combination treatment with LEE and TMT | Drug | Advanced or metastatic solid tumors |
Primary outcome
Incidence of dose limiting toxicities (DLTs)
Time frame: 21-day cycle one of treatment
Phase Ib part: The primary variable is the incidence of DLTs during the first 21 days of therapy. Estimation of the MTD of the combination treatment will be based upon the estimation of the probability of DLT during the first 21 days of therapy for patients in the DDS.
Objective Response Rate (ORR)
Time frame: Until progression of disease up to 1 year
Phase II part: The primary variable used to evaluate the efficacy of the ribociclib and trametinib combination is the ORR, defined as the proportion of patients with a best overall confirmed CR or PR, as assessed per RECIST 1.1 by investigator assessment.
6 secondary outcomes
Duration of response (DOR)
Time frame: Until progression of disease up to 1 year
Time to response
Time frame: Until progression of disease up to 1 year
Disease control rate
Time frame: Until progression of disease up to 1 year
Progression disease rate
Time frame: Until progression of disease up to 1 year
Progression free survival
Time frame: Until progression of disease up to 1 year
overall survival
Time frame: Until death up to 1 year
Results and safety
The study was stopped early (reason given: Company decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2020.
- Results for CTMT212X2106 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
15 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ribociclib and Trametinib in people with Solid Tumors for Phase Ib and Pancreatic Cancer for Phase II, run by Novartis Pharmaceuticals at 15 sites in 7 countries.
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 12 inclusion and 26 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 21 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, Canada, Germany, Netherlands, Australia and 2 more countries. 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?
The study was stopped early (reason given: Company decision). Results are not available in the source record.
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?
Incidence of dose limiting toxicities (DLTs) (time frame: 21-day cycle one of treatment). 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 21 Dec 2020.