Colorectal Cancer MetastaticPhase 1/2NCT04031872
LY3200882 and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer (EORTC1615)
A Phase 1/2 study testing LY3200882 in people with Colorectal Cancer Metastatic, run by The Netherlands Cancer Institute.
Trial summary
Part I of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of LY3200882/capecitabine as second line treatment in patients with 5-FU or capecitabine resistant CRC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- LY3200882
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2020to 1 Jan 2020
- Phase
- Phase 1/2
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
- Histological or cytological proof of CRC;
- Disease progression or relapse upon at least one line of treatment for advanced CRC with fluoropyrimidine containing chemotherapy as single agent or in combination (combinations with oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab are allowed);
- Written documentation of activated TGF-β signature-like gene signature, as determined by the validated assay of Agendia;
- Age ≥ 18 years;
- Able and willing to give written informed consent;
- WHO performance status of ≤ 1;
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- LVEF ≥ 55%;
- Able and willing to undergo blood sampling for PK and PD analysis;
- Able and willing to undergo tumor biopsies before start, during treatment and at the end of treatment
- Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity;
- Evaluable disease according to RECIST 1.1 criteria (measurable disease for the phase II part; evaluable disease is sufficient for the phase I part);
- Minimal acceptable safety laboratory values
- ANC of ≥ 1.5 x 109 /L
- Platelet count of ≥ 100 x 109 /L
- Hepatic function as defined by serum bilirubin ≤ 1.5 x ULN, ALAT and ASAT ≤ 3.0 x ULN, or ALAT and ASAT ≤ 5 x ULN in patients with liver metastases
- Renal function as defined by serum creatinine ≤1.5 x ULN
- Creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula or MDRD);
- Negative pregnancy test (urine or serum) for female patients with childbearing potential.
Who cannot join
- Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment;
- Known or suspected dihydropirimidine dehydrogenase deficit (Mutant for DPD*2A genotype, 1236 GA genotype, 1679TG genotype and 2846A>T genotype);
- Symptomatic or untreated leptomeningeal disease;
- Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enrol. Brain metastasis must be stable with verification by imaging (e.g. brain MRI or CT (<21 days before start of treatment) completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs or corticosteroids;
- History of cardiac disease, including myocardial infarction within 6 months before study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension, major cardiac abnormalities, a predisposition for developing aneurysms including family history of aneurysms, Marfan syndrome, bicuspid aortic valve, or evidence of damage to the large vessels of the heart.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LY3200882 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection);
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- Woman who are pregnant or breast feeding;
- Radio- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed;
- Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery;
- Active infection requiring systemic antibiotics or uncontrolled infectious disease;
- Patients with a known history of hepatitis B or C or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
- Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study;
- Known hypersensitivity to one of the study drugs or excipients.
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year (when used consistently and correctly) during the treatment period and for at least 90 days after the last dose of LY3200882 and/or capecitabine. More information is available in section 5.2.4.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined in section 5.2.4.
About this study
Official title: MoTriColor: Phase I/II Study With LY3200882 Combined With Capecitabine in Patients With Advanced Chemotherapy Resistant Colorectal Cancer and an Activated TGF-beta Signature
Part I of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of LY3200882/capecitabine as second line treatment in patients with 5-FU or capecitabine resistant CRC. Part II is designed to obtain proof of principle of the LY3200882 plus capecitabine combination in patients with chemo-resistant CRC. The combination of LY3200882 plus capecitabine will be given as second line therapy in the phase II part of this study.
Patients with chemotherapy resistant activated TGF-β signature-like tumors will have received a fluoropyrimidine (5FU or capecitabine) in the first line of chemotherapy, usually combined with oxaliplatin and, depending upon local hospital preferences or national guidelines, also bevacizumab, or cetuximab/panitumumab if the tumor is KRAS wild type. Addition of LY3200882 to capecitabine should thus result in reversal of unresponsiveness, which is the first step in exploring this concept in the clinic. Capecitabine can be used as single agent in advanced CRC and is thus attractive for this study concept. If proof of principle is achieved also other tumor types can be explored with this genetic makeup, such as non-small cell lung cancer (NSCLC) in second line of treatment after platinum doublet therapy in first line, usually cisplatin/carboplatin-pemetrexed in non-squamous and cisplatin/carboplatin-gemcitabine or cisplatin/carboplatin-paclitaxel in squamous type NSCLC.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- LY3200882
- Keywords
- TGF- beta activated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3200882Drug
Also called Capecitabine
Combination treatment with LY3200882 and capecitabine
| Study group | Role | What they receive |
|---|---|---|
| TGF-beta activated colorectal cancer | Experimental | TGF-beta activated advanced colorectal cancer with LY3200882 and capecitabine Receives: Drug: LY3200882 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: The recommended phase 2 dose (RP2D) of galunisertib plus capecitabine in patients with chemotherapy resistant activated TGF-β signature-like CRC.
Measured: 6 months
Phase II: Response rate (RR) of galunisertib in combination with capecitabine in patients with chemotherapy resistant activated TGF-β signature-like CRC.
Measured: 12 months
Secondary outcomes (8)
The incidence and severity of adverse events
Measured: 12 months
Duration of response
Measured: 12 months
Time to response
Measured: 12 months
Overall survival (phase II only)
Measured: 12 months
Plasma concentrations of LY3200882 in combination with chemotherapy
Measured: 12 months
Gene alterations/expression profiles (e.g. baseline, relapse) in tumor tissue upon progression
Measured: 12 months
Baseline molecular status of potential predictive markers of tumor response
Measured: 12 months
Progression free survival (phase II only)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2019
- Study start1 Jan 2020
- Primary completion1 Jan 2020
- Study completion1 Jan 2020
Why it stopped: No IMP available and Covid
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Vall d'Hebron Institute of Oncology, Agendia, European Organisation for Research and Treatment of Cancer - EORTC, Azienda Ospedaliera Niguarda Cà Granda, Fundación para la Investigación del Hospital Clínico de Valencia, University of Campania Luigi Vanvitelli, University of Turin, Italy, Eli Lilly and Company, Catalan Institute of Health, Universitaire Ziekenhuizen KU Leuven
- Responsible party
- Sponsor
- Investigators
- J Tabernero, Prof, Principal investigator, VHIOR Bernards, Prof, Principal investigator, NKI-AvLR Salazar, MD, PhD, Principal investigator, ICOS Siena, Prof, Principal investigator, ONCGA Cervantes, Prof, Principal investigator, Instituto de Investigacion Sanitaria INCLIVAF Ciardello, Prof, Principal investigator, UNINA2A Bardelli, Prof, Principal investigator, UNITOS Tejpar, Prof, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04031872
- Sponsor's protocol ID
- M19TGA
- Status last verified
- Aug 2025
- First submitted
- 22 Jul 2019
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No