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Regorafenib in Combination With Paclitaxel in Advanced Oesophagogastric Carcinoma (REPEAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02406170
Recruitment Status : Completed
First Posted : April 2, 2015
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary:
Patients with advanced oesophagogastric cancer (OCG) have a very poor prognosis. After progression on first line therapy, second line chemotherapy with paclitaxel and a VEGF-R2 targeting antibody has a proven benefit on survival. However, no data are available on the combination of paclitaxel with kinase inhibitors in advanced OGC. Here the investigators propose a Phase 1b study to assess the tolerability of regorafenib (an oral multi kinase inhibitor) in combination with paclitaxel and to assess the uptake of paclitaxel in OCG metastasis.

Condition or disease Intervention/treatment Phase
Esophageal Neoplasms Stomach Neoplasms Neoplasm Metastasis Drug: Regorafenib Drug: Paclitaxel Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The REPEAT Trial: Regorafenib in Combination With Paclitaxel in Advanced Oesophagogastric Carcinoma, a Phase 1b Study
Study Start Date : April 2015
Actual Primary Completion Date : October 2019
Actual Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Regorafenib+Paclitaxel
Regorafenib tolerability will be tested in a dose escalation scheme with a cytotoxic backbone of paclitaxel 80mg/m2.
Drug: Regorafenib
The dose of regorafenib will be escalated in fixed increments to establish the maximum tolerated dose (MTD) from day 1-21 against a cytotoxic backbone of paclitaxel 80mg/m2 on days 1, 8 and 15 of a 28 day cycle
Other Name: dose escalation scheme

Drug: Paclitaxel
Paclitaxel will be administered in combination with regorafenib to serve as a cytotoxic backbone, it will be given in a dose of 80mg/m2 on days 1,8 and 15 of a 28 day cycle.




Primary Outcome Measures :
  1. Toxicity graded according to NCI Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: 4 weeks ]
    graded according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE).


Secondary Outcome Measures :
  1. Paclitaxel concentration in tumor biopsy [ Time Frame: 2 year ]
  2. Composite Paclitaxel pharmacokinetics [ Time Frame: 2 year ]
    Area under the plasma concentration versus time curve (AUC), Peak plasma concentration (Cmax)

  3. Expression of regorafenib targets in tumor biopsy samples [ Time Frame: 2 year ]
  4. Progression free survival [ Time Frame: 2 years ]
  5. Overall survival [ Time Frame: 2 year ]


Information from the National Library of Medicine

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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:

  • Patient must understand, be willing to give consent, and sign a written informed consent form prior to undergoing any study-specific procedure
  • Male or female and ≥ 18 years of age
  • Metastatic or non-resectable adeno- or squamous-cell carcinoma of the stomach or oesophagus who failed on first line cytotoxic treatment with a fluoropyrimidine and platinum compound
  • Tumor accessible for repeated biopsies
  • Measurable or evaluable disease
  • Life expectancy of at least 12 weeks
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Have adequate bone marrow, liver function, and renal function as measured by pre-specified laboratory assessments conducted within 7 days prior to the start of study treatment
  • If female and of childbearing potential, have a NEGATIVE result on a pregnancy test performed a maximum of 7 days before start of study treatment
  • If female and of childbearing potential or if male, must agree to use adequate contraception based on the judgment of the investigator or a designated associate from the date on which the ICF is signed until 6 months after the last dose of study drug.

Exclusion Criteria:

  • Prior treatment with regorafenib
  • Contra-indications for repeated biopsies
  • Dementia or altered mental status that would prohibit the understanding and giving of informed consent
  • Inadequate caloric- and/or fluid intake.
  • Pre-existing motor or sensory neurotoxicity greater than WHO grade 1
  • Have unresolved toxicity higher than National Cancer Institute-Common Terminology for Adverse Events version 4.0 (NCI-CTCAE v 4.0) Grade 1 attributed to any prior therapy/procedure, excluding alopecia.
  • Have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment
  • If female and of childbearing potential, be engaged in breast feeding
  • Be unable to swallow oral tablets
  • Have congestive heart failure classified as New York Heart Association Class 2 or higher
  • Have had unstable angina or new-onset angina ≤ 3 months prior to screening
  • Have had a myocardial infarction ≤ 6 months prior to start of study treatment
  • Have cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
  • Have uncontrolled hypertension despite optimal medical management
  • Have pheochromocytoma
  • Have had arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 3 months prior to the initiation of study treatment
  • Have an ongoing infection ≥ Grade 2 (NCI-CTCAE v 4.0)
  • Have a known history of human immunodeficiency virus infection
  • Have either active hepatitis B or C or chronic hepatitis B or C requiring treatment
  • Have a seizure disorder requiring medication
  • Have currently suspected brain metastases
  • Have a history of organ allograft
  • Have evidence or history of any bleeding diathesis (including mild hemophilia), irrespective of severity
  • Have had a hemorrhage or a bleeding event > Grade 3 ( NCI-CTCAE v 4.0) within 4 weeks prior to the start of study treatment
  • Have a non-healing wound, ulcer, or bone fracture
  • Have interstitial lung disease with ongoing signs and symptoms at the time informed consent is obtained
  • Have any other serious illness or medical condition that could jeopardize the safety of the patient
  • Have an unstable illness or medical condition that could jeopardize the safety of the patient and/or his/her compliance
  • Have a substance abuse, medical, psychological, or social condition that may interfere with participation in the study or evaluation of the study results
  • Have a known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
  • Have any malabsorption condition
  • Using and unable to stop medication that are prohibited due to interaction
  • Unwilling to stop pommelos, citrus fruit and herbal medicine inducing or inhibiting the CYP system

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): NCT02406170


Locations
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Netherlands
Academic Medical Center, Medical Oncology
Amsterdam, Netherlands, 1100 DD
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
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Principal Investigator: Hanneke WM van Laarhoven, MD,PHD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: H.W.M. van Laarhoven, Prof.Dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02406170    
Other Study ID Numbers: NL.51666
First Posted: April 2, 2015    Key Record Dates
Last Update Posted: October 22, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Stomach Neoplasms
Esophageal Neoplasms
Neoplastic Processes
Pathologic Processes
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action