Galunisertib Combined With Capecitabine in Advanced CRC With PM

NCT05700656 | Recruiting Phase 1 DMC

• 1 other identifier: M22TGA
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Colorectal Cancer Metastatic; Peritoneal Carcinomatosis

Keywords

colorectal cancer; metastatic colorectal cancer; peritonitis carcinomatosa

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  through study completion, an average of 6 months per patient

Secondary Outcomes (6)

• Duration of response (DOR)

  through study completion, an average of 6 months per patient

• Time to response (TTR)

  From date of study entry until first objective response, an average of 2 months

• Progression free survival (PFS)

  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)

  From date of study entry until date of death from any cause, assessed up to 5 years

• Cmax, Tmax, AUC, T0.5, MTD

  14 days

Study Arms (1)

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

Drug: Galunisertib plus capecitabine

Interventions

Galunisertib plus capecitabine DRUG

Combination therapy with galunisertib plus capecitabine

Galunisertib plus capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological proof of CRC with at least confirmed peritoneal metastases (presence of additional extraperitoneal metastases is 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;
• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Amsterdam UMC: collaborator

Study Sites (2)

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, 1081 HV, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Peritoneal Neoplasms; Colorectal Neoplasms

Interventions

LY-2157299; Capecitabine

Condition Hierarchy (Ancestors)

Abdominal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Alaa Embaby, MD

CONTACT

0031205129111; a.embaby@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 26, 2023
• Study Start: July 28, 2023
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: July 22, 2024

Record last verified: 2024-07

Locations

NL (2)