Regorafenib in Combination With Paclitaxel in Advanced Oesophagogastric Carcinoma

NCT02406170 | Completed Phase 1 DMC

• 1 other identifier: NL.51666
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Neoplasm Metastasis

Outcome Measures

Primary Outcomes (1)

• Toxicity graded according to NCI Common Terminology Criteria for Adverse Events Version 4.0

  graded according to NCI Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE).

  4 weeks

Secondary Outcomes (5)

• Paclitaxel concentration in tumor biopsy

  2 year

• Composite Paclitaxel pharmacokinetics

  2 year

• Expression of regorafenib targets in tumor biopsy samples

  2 year

• Progression free survival

  2 years

• Overall survival

  2 year

Study Arms (1)

Regorafenib+Paclitaxel

EXPERIMENTAL

Regorafenib tolerability will be tested in a dose escalation scheme with a cytotoxic backbone of paclitaxel 80mg/m2.

Drug: Regorafenib; Drug: Paclitaxel

Interventions

Regorafenib DRUG

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

Also known as: dose escalation scheme

Regorafenib+Paclitaxel

Paclitaxel DRUG

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.

Regorafenib+Paclitaxel

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Center, Medical Oncology

Amsterdam, 1100 DD, Netherlands

Location

Related Publications (1)

• Stroes CI, Schokker S, Khurshed M, van der Woude SO, Mathot RA, Slingerland M, de Vos-Geelen J, Zucchetti M, Matteo C, van Dijk E, Ylstra B, Thijssen V, Derks S, Godefa T, Dijksterhuis W, Breimer GE, van Delden OM, Verhoeven RH, Meijer SL, Bijlsma MF, van Laarhoven HW. A phase Ib/II study of regorafenib and paclitaxel in patients with beyond first-line advanced esophagogastric carcinoma (REPEAT). Ther Adv Med Oncol. 2022 Jun 28;14:17588359221109196. doi: 10.1177/17588359221109196. eCollection 2022.

  PMID: 35782751 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Neoplasm Metastasis

Interventions

regorafenib; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Hanneke WM van Laarhoven, MD,PHD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr.

Study Record Dates

• First Submitted: March 26, 2015
• First Posted: April 2, 2015
• Study Start: April 1, 2015
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

NL (1)