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Trial record 7 of 297 for:    colon cancer AND Capecitabine AND chemotherapy

LY3200882 and Capecitabine in Advanced Resistant TGF-beta Activated Colorectal Cancer (EORTC1615)

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ClinicalTrials.gov Identifier: NCT04031872
Recruitment Status : Not yet recruiting
First Posted : July 24, 2019
Last Update Posted : July 24, 2019
Sponsor:
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 Leuven
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Drug: LY3200882 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : February 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: TGF-beta activated colorectal cancer
TGF-beta activated advanced colorectal cancer with LY3200882 and capecitabine
Drug: LY3200882
Combination treatment with LY3200882 and capecitabine
Other Name: Capecitabine




Primary Outcome Measures :
  1. 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 ]
  2. Phase II: Response rate (RR) of galunisertib in combination with capecitabine in patients with chemotherapy resistant activated TGF-β signature-like CRC. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. The incidence and severity of adverse events [ Time Frame: 12 months ]
  2. Duration of response [ Time Frame: 12 months ]
  3. Time to response [ Time Frame: 12 months ]
  4. Overall survival (phase II only) [ Time Frame: 12 months ]
  5. Plasma concentrations of LY3200882 in combination with chemotherapy [ Time Frame: 12 months ]
  6. Gene alterations/expression profiles (e.g. baseline, relapse) in tumor tissue upon progression [ Time Frame: 12 months ]
  7. Baseline molecular status of potential predictive markers of tumor response [ Time Frame: 12 months ]
  8. Progression free survival (phase II only) [ Time Frame: 12 months ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histological or cytological proof of CRC;
  2. 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);
  3. Written documentation of activated TGF-β signature-like gene signature, as determined by the validated assay of Agendia;
  4. Age ≥ 18 years;
  5. Able and willing to give written informed consent;
  6. WHO performance status of ≤ 1;
  7. LVEF ≥ 55%;
  8. Able and willing to undergo blood sampling for PK and PD analysis;
  9. Able and willing to undergo tumor biopsies before start, during treatment and at the end of treatment
  10. Life expectancy ≥ 3 months allowing adequate follow up of toxicity evaluation and anti-tumor activity;
  11. Evaluable disease according to RECIST 1.1 criteria (measurable disease for the phase II part; evaluable disease is sufficient for the phase I part);
  12. Minimal acceptable safety laboratory values

    1. ANC of ≥ 1.5 x 109 /L
    2. Platelet count of ≥ 100 x 109 /L
    3. 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
    4. Renal function as defined by serum creatinine ≤1.5 x ULN
    5. Creatinine clearance ≥ 50 ml/min (by Cockcroft-Gault formula or MDRD);
  13. Negative pregnancy test (urine or serum) for female patients with childbearing potential.

Exclusion Criteria:

  1. Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment;
  2. Known or suspected dihydropirimidine dehydrogenase deficit (Mutant for DPD*2A genotype, 1236 GA genotype, 1679TG genotype and 2846A>T genotype);
  3. Symptomatic or untreated leptomeningeal disease;
  4. 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;
  5. 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.
  6. 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);
  7. Woman who are pregnant or breast feeding;
  8. Radio- or chemotherapy within the last 2 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed;
  9. 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;
  10. Active infection requiring systemic antibiotics or uncontrolled infectious disease;
  11. Patients with a known history of hepatitis B or C or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
  12. 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;
  13. Known hypersensitivity to one of the study drugs or excipients.
  14. 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.
  15. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04031872


Contacts
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Contact: Neeltje Steeghs, MD, PhD +310205129111 n.steeghs@nki.nl
Contact: Sanne Huijberts, MD +310205129111 s.huijberts@nki.nl

Sponsors and Collaborators
The Netherlands Cancer Institute
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 Leuven
Investigators
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Principal Investigator: J Tabernero, Prof VHIO
Principal Investigator: R Bernards, Prof NKI-AvL
Principal Investigator: R Salazar, MD, PhD ICO
Principal Investigator: S Siena, Prof ONCG
Principal Investigator: A Cervantes, Prof INCLIVA
Principal Investigator: F Ciardello, Prof UNINA2
Principal Investigator: A Bardelli, Prof UNITO
Principal Investigator: S Tejpar, Prof UZ Leuven

Additional Information:
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Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT04031872     History of Changes
Other Study ID Numbers: M19TGA
First Posted: July 24, 2019    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The Netherlands Cancer Institute:
TGF- beta activated
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Capecitabine
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents