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Colorectal Cancer MetastaticPhase 1/2EORTC1615NCT03470350

Galunisertib and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer

A Phase 1/2 study testing Galunisertib in people with Colorectal Cancer Metastatic, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Part I of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of galunisertib/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?
Galunisertib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteNetherlands
Study dates
24 Aug 2018to 1 Jun 2020
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 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 first line of treatment (maximum lines of treatment is one for phase I and phase II of this study) 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 galunisertib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection);
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  • Woman who are pregnant or breast feeding;
  • Unreliable contraceptive methods. Both men and women enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: condom, sterilization, other barrier contraceptive measures preferably in combination with condoms);
  • 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.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Antoni van Leeuwenhoek (NKI-AVL)

    Amsterdam, North Holland, 1066 CX

Other trials in Netherlands

About this study

Official title: MoTriColor: Phase I/II Study With Galunisertib (LY2157299) 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 galunisertib/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 galunisertib plus capecitabine combination in patients with chemo-resistant CRC. The combination of galunisertib 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 galunisertib 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.

Being tested
Galunisertib
Keywords
TGF-beta activatied

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GalunisertibDrug

    Also called Capecitabine

    treatment with capecitabine and galunisertib

Study groups in NCT03470350
Study groupRoleWhat they receive
TGF-beta activated colorectal cancerExperimentalTGF-beta activated advanced colorectal cancer treated with galunisertib and capecitabine
Receives: Drug: Galunisertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

  2. Phase II: Response rate (RR) of galunisertib in combination with capecitabine in patients with chemotherapy resistant activated TGF-β signature-like CRC.

    Measured: 15 months

Secondary outcomes (8)

  1. The incidence and severity of adverse events

    Measured: 15 months

  2. duration of response

    Measured: 15 months

  3. time to response

    Measured: 15 months

  4. overall survival (phase II only)

    Measured: 15 months

  5. progression free survival (phase II only)

    Measured: 15 months

  6. Plasma concentrations of galunisertib in combination with chemotherapy

    Measured: 15 months

  7. Gene alterations/expression profiles (e.g. baseline, relapse) in tumor tissue upon progression

    Measured: 15 months

  8. Baseline molecular status of potential predictive markers of tumor response

    Measured: 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2018
  2. Study start24 Aug 2018 (estimated)
  3. Primary completion1 Jun 2020 (estimated)
  4. Study completion1 Jun 2020 (estimated)

Why it stopped: No study drug available. Same concept with new study drug will be explored in M19TGA study

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03470350
Sponsor's protocol ID
M16TGA
Other IDs
2016-002349-50, 2016
Acronym
EORTC1615
Status last verified
Jul 2019
First submitted
14 Feb 2018
Last updated
24 Jul 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Galunisertib in people with Colorectal Cancer Metastatic, run by The Netherlands Cancer Institute at 1 site 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 18 inclusion and 14 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: withdrawn, as of the sponsor's last update on 24 Jul 2019. 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 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Phase I: The recommended phase 2 dose (RP2D) of galunisertib plus capecitabine in patients with chemotherapy resistant activated TGF-β signature-like CRC. (time frame: 6 months). 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?

On the ClinicalTrials.gov record for NCT03470350.

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 24 Jul 2019.

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