Colorectal Cancer MetastaticPhase 1/2NCT05700656
Galunisertib Combined With Capecitabine in Advanced CRC With PM
A Phase 1/2 study testing Galunisertib plus capecitabine in people with Colorectal Cancer Metastatic and Peritoneal Carcinomatosis, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
Trial summary
This is a two-center open-label non-randomized proof of principle study consisting of a dose-finding part (phase I) and phase II study with Simon two-stage design investigating the anti-tumor activity of the combination of capecitabine and galunisertib in patients with colorectal cancer with peritoneal metastases. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic, Peritoneal Carcinomatosis
- What is being tested?
- Galunisertib plus capecitabine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesNetherlands
- Study dates
- 28 Jul 2023to Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 with at least confirmed peritoneal metastases (presence of additional extraperitoneal metastases is allowed);
- Disease progression or relapse upon treatment for advanced CRC with fluoropyrimidine containing chemotherapy as single agent or in combination with other anti-cancer drugs, with no treatment options at time of inclusion (combinations with oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab are allowed);
- Age ≥ 18 years;
- Able and willing to give written informed consent and informed consent form must have been signed before start of the trial;
- WHO performance status of ≤1;
- Able and willing to undergo blood sampling for PK analysis;
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- Able and willing to undergo tumor biopsy before start, during treatment and at the end of treatment;
- Life expectancy > 3 months allowing adequate follow up of toxicity 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.
- Able and willing to swallow tablets.
Who cannot join
- Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment and/or radio- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed; except radiotherapy focused on the liver;
- Known or suspected complete or partial dihydropyrimidine dehydrogenase deficiency (Mutant for DPD*2A genotype, 1236G>A genotype, 1679T>G 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 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 first dose of study medication, 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;
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- Treatment with CYP3A4 inducers or inhibitors and/or concomitant treatment with CYP2C9 substrates with narrow therapeutic window, including but not limited to vitamin K antagonizing anticoagulants (e.g. acenocoumarol, phenprocoumon and warfarin) and phenytoin is not allowed;
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral galunisertib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, major small bowel surgery);
- Woman who are pregnant or breast feeding;
- 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 galunisertib and/or capecitabine.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Netherlands Cancer Institute
Amsterdam, 1066CX
Amsterdam UMC
Amsterdam, 1081 HV
About this study
Official title: Phase I/II Study With Galunisertib Combined With Capecitabine in Patients With Advanced Chemotherapy Resistant Colorectal Cancer With Peritoneal Metastases
This is a two-center open-label non-randomized proof of principle study consisting of a dose-finding part (phase I) and phase II study with Simon two-stage design investigating the anti-tumor activity of the combination of capecitabine and galunisertib in patients with colorectal cancer with peritoneal metastases.
Read the detailed description
This is a two-center pharmacological open-label non-randomized proof of principle study consisting of two parts: a phase I study evaluating the RP2D of galunisertib in combination with capecitabine; and a phase II study investigating the anti-tumor activity and safety of galunisertib in combination with capecitabine in advanced colorectal cancer (CRC) with peritoneal metastases (PM).
In phase II of the study a Simon two-stage design will be used. 15 patients will be treated with the galunisertib/capecitabine combination. If at least 2 out of 15 patients respond, an additional cohort of 10 patients will be included to a total of 25 patients. With 6 or more responses, the treatment will be declared to be of sufficient activity and with 5 or less it will be declared of insufficient activity.
The galunisertib dose will be 150 mg twice daily (BID) for the first 14 days of every 4-week cycle, which is the maximum tolerated dose when given as single agent (except of day 1 of cycle 1: single dose of galunisertib 150 mg for PK analysis, from day 2: 150 mg BID).
Capecitabine will be dosed during every 14-day on time of galunisertib at 1000 mg/m2 BID, which is the labelled dose as monotherapy and will in case of toxicities be reduced according to standard care.
Clinical assessments will be performed routinely to monitor safety. Anti-tumor activity will be measured by CT scan according to RECIST 1.1 criteria. Tumor biopsies will be obtained for exploratory objectives.
- Being tested
- Galunisertib plus capecitabine
- Keywords
- colorectal cancer, metastatic colorectal cancer, peritonitis carcinomatosa
- Medical subject headings
- Peritoneal Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Galunisertib plus capecitabineDrug
Combination therapy with galunisertib plus capecitabine
| Study group | Role | What they receive |
|---|---|---|
| Galunisertib plus capecitabine | Experimental | Galunisertib 150 mg BID for 14 days in a 28-day cycle plus capecitabine 1000 mg/m2 BID for 14 days in a 28-day cycle Receives: Drug: Galunisertib plus capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events according to CTCAE v5.0, dose limiting toxicities
To determine the safety and RP2D of galunisertib plus capecitabine in patients with advanced chemotherapy resistant CRC with peritoneal metastases
Measured: 28 days
Objective response rate (ORR)
To determine the anti-tumor activity as measured by ORR of galunisertib plus capecitabine in patients with advanced chemotherapy resistant CRC with PM.
Measured: through study completion, an average of 6 months per patient
Secondary outcomes (6)
Duration of response (DOR)
Time from first response until progression
Measured: through study completion, an average of 6 months per patient
Time to response (TTR)
Time from start of treatment until first objective response
Measured: From date of study entry until first objective response, an average of 2 months
Progression free survival (PFS)
Time from start of the treatment until progression
Measured: From date of study entry until the date of first documented progression of date of death from any cause, whichever comes first, assessed up to 5 years
Overall survival (OS)
Time from start of the study until death
Measured: From date of study entry until date of death from any cause, assessed up to 5 years
Cmax, Tmax, AUC, T0.5, MTD
Pharmacokinetic profile of galunisertib
Measured: 14 days
RNA sequencing, THG-b signaling, other
Exploratory genomic analyses to determine biomarkers for response and resistance to the combination of galunisertib and capecitabine
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start28 Jul 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
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.
- More trials run by The Netherlands Cancer InstituteThe 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
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05700656
- Sponsor's protocol ID
- M22TGA
- Status last verified
- Jul 2026
- First submitted
- 3 Jan 2023
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study With Galunisertib Combined With Capecitabine in Patients With Advanced Chemotherapy Resistant Colorectal Cancer With Peritoneal Metastases
- ClinicalTrials.gov ID
- NCT05700656
- Acronym / sponsor ID
- M22TGA
- Keywords
- colorectal cancer, metastatic colorectal cancer, peritonitis carcinomatosa
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- Amsterdam UMC
- Study start
- 28 Jul 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 26 Jan 2023 (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.
This is a two-center open-label non-randomized proof of principle study consisting of a dose-finding part (phase I) and phase II study with Simon two-stage design investigating the anti-tumor activity of the combination of capecitabine and galunisertib in patients with colorectal cancer with peritoneal metastases.
Detailed description
This is a two-center pharmacological open-label non-randomized proof of principle study consisting of two parts: a phase I study evaluating the RP2D of galunisertib in combination with capecitabine; and a phase II study investigating the anti-tumor activity and safety of galunisertib in combination with capecitabine in advanced colorectal cancer (CRC) with peritoneal metastases (PM).
In phase II of the study a Simon two-stage design will be used. 15 patients will be treated with the galunisertib/capecitabine combination. If at least 2 out of 15 patients respond, an additional cohort of 10 patients will be included to a total of 25 patients. With 6 or more responses, the treatment will be declared to be of sufficient activity and with 5 or less it will be declared of insufficient activity.
The galunisertib dose will be 150 mg twice daily (BID) for the first 14 days of every 4-week cycle, which is the maximum tolerated dose when given as single agent (except of day 1 of cycle 1: single dose of galunisertib 150 mg for PK analysis, from day 2: 150 mg BID).
Capecitabine will be dosed during every 14-day on time of galunisertib at 1000 mg/m2 BID, which is the labelled dose as monotherapy and will in case of toxicities be reduced according to standard care.
Clinical assessments will be performed routinely to monitor safety. Anti-tumor activity will be measured by CT scan according to RECIST 1.1 criteria. Tumor biopsies will be obtained for exploratory objectives.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Galunisertib plus capecitabine | Experimental | Drug: Galunisertib plus capecitabineGalunisertib 150 mg BID for 14 days in a 28-day cycle plus capecitabine 1000 mg/m2 BID for 14 days in a 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histological or cytological proof of CRC with at least confirmed peritoneal metastases (presence of additional extraperitoneal metastases is allowed);
- Disease progression or relapse upon treatment for advanced CRC with fluoropyrimidine containing chemotherapy as single agent or in combination with other anti-cancer drugs, with no treatment options at time of inclusion (combinations with oxaliplatin, irinotecan, bevacizumab and cetuximab/panitumumab are allowed);
- Age ≥ 18 years;
- Able and willing to give written informed consent and informed consent form must have been signed before start of the trial;
- WHO performance status of ≤1;
Key exclusion criteria (16 listed)
- Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment and/or radio- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed; except radiotherapy focused on the liver;
- Known or suspected complete or partial dihydropyrimidine dehydrogenase deficiency (Mutant for DPD*2A genotype, 1236G>A genotype, 1679T>G 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 completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs or corticosteroids;
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 |
|---|---|---|
| Galunisertib plus capecitabineCombination therapy with galunisertib plus capecitabine | Drug | Galunisertib plus capecitabine |
Primary outcome
Number of participants with treatment-related adverse events according to CTCAE v5.0, dose limiting toxicities
Time frame: 28 days
To determine the safety and RP2D of galunisertib plus capecitabine in patients with advanced chemotherapy resistant CRC with peritoneal metastases
Objective response rate (ORR)
Time frame: through study completion, an average of 6 months per patient
To determine the anti-tumor activity as measured by ORR of galunisertib plus capecitabine in patients with advanced chemotherapy resistant CRC with PM.
6 secondary outcomes
Duration of response (DOR)
Time frame: through study completion, an average of 6 months per patient
Time to response (TTR)
Time frame: From date of study entry until first objective response, an average of 2 months
Progression free survival (PFS)
Time frame: From date of study entry until the date of first documented progression of date of death from any cause, whichever comes first, assessed up to 5 years
Overall survival (OS)
Time frame: From date of study entry until date of death from any cause, assessed up to 5 years
Cmax, Tmax, AUC, T0.5, MTD
Time frame: 14 days
RNA sequencing, THG-b signaling, other
Time frame: through study completion, an average of 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
- Individual participant dataSharing planned: Undecided
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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.
2 sites 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 Galunisertib plus capecitabine in people with Colorectal Cancer Metastatic and Peritoneal Carcinomatosis, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
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 17 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
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?
Number of participants with treatment-related adverse events according to CTCAE v5.0, dose limiting toxicities (time frame: 28 days). 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 13 Jul 2026.