Regorafenib in Combination With Paclitaxel in Advanced Oesophagogastric Carcinoma

• Status: Completed
• Trial end date: 2019-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Treatments: Albumin-Bound Paclitaxel; Paclitaxel

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