Phase Ib Study of SUnitinib Alternating With REgorafenib in Patients With Metastatic and/or Unresectable GIST

NCT02164240 | Completed Phase 1 Results DMC

• 1 other identifier: 14-149
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the safety and tolerability of sunitinib alternating with regorafenib in participants with advanced gastrointestinal stromal tumor GIST, if the standard approved therapies (imatinib, sunitinib and regorafenib) have failed to control the disease. Additionally, this study seeks to determine the highest dose that can be given safely for this combination of drugs.

Conditions

Gastrointestinal Stromal Tumor

Keywords

Gastrointestinal Stromal Tumor

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Serious and Non-Serious Adverse Events

  Dose-escalation cohort is to determine the frequency and characteristics of DLTs of alternation of sunitinib and regorafenib at each dose level during the first cycle of therapy. Toxicity will be graded accordingly with NCI CTCAE version 4.0

  Up to Day 28

Secondary Outcomes (2)

• Percentage of Participants With Clinical Benefit

  16 weeks

• Median Progression Free Survival (mPFS)

  From date of registration until date of protocol-defined progression while on this protocol, assessed up to 6 months

Study Arms (1)

Sunitinib alternated with Regorafenib

EXPERIMENTAL

The treatment cycle is defined as 28 days. Treatment consists of 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each cycle. The starting dose level is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage and recommended phase II dose is determined. An alternative scheme of 4-week cycles of the same regimen but with 21 days of dosing followed by 7 days of rest will be studied in case of toxicities during d 22-28 of the starting 4-weeks continuous cycles. Tumor assessments performed at baseline and after every two dosing cycles to assess response. Toxicity monitored throughout the study.

Drug: Sunitinib; Drug: Regorafenib

Interventions

Sunitinib DRUG

Intervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops.

Also known as: Sutent

Sunitinib alternated with Regorafenib

Regorafenib DRUG

Intervention Description: 3 days of once daily sunitinib alternating with 4 days of once daily regorafenib throughout each 28 day cycle. The starting dose level (level 1) is sunitinib 37.5 mg/d and regorafenib 120 mg/d, and doses will be escalated in subsequent cohorts following a classical 3+3 design up to sunitinib 50 mg/d and regorafenib 160 mg/d or until maximum tolerable dosage (MTD) and recommended phase II dose (RP2D) is determined. Number of Cycles: until progression or unacceptable toxicity develops.

Also known as: Stivarga

Sunitinib alternated with Regorafenib

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age at the time of study entry.
• Histologically confirmed metastatic and/or unresectable GIST. Patients must demonstrate prior failure to at least imatinib, sunitinib and regorafenib (4th line and beyond). Any number of previous therapies for GIST is allowed.
• Measurable disease per modified RECIST 1.1. A lesion in a previously irradiated area is ineligible to be considered as measurable disease unless there is objective evidence of progression of the lesion prior to study enrollment.
• ECOG performance status 0 or 1 (see Appendix A).
• Participants must have adequate organ and marrow function as outlined in the protocol.
• Patients must be able to swallow oral medication.
• Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug.
• Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Use of any approved tyrosine kinase inhibitors or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study drugs.
• Patients with intolerance to sunitinib and/or regorafenib.
• Participants who have had radiotherapy within 4 weeks prior to study entry.
• Major surgery, or significant traumatic injury within 4 weeks prior to study entry.
• Presence of symptomatic or uncontrolled brain or central nervous system metastases.
• Known or suspected allergy to the investigational agent or any agent given in association with this trial.
• Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy OR other primary malignancy is neither currently clinically significant nor requiring active intervention.
• Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• History of clinically significant cardiac disease or congestive heart failure \> NYHA class 2 (See Appendix C). Patients must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
• Hypertension as defined by systolic blood pressure \>140 mmHg or diastolic blood pressure \> 90 mmH despite optimal medical management.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication (except for adequately treated catheter-related venous thrombosis occurring more than 1 month before the start of study medication).
• Patients with evidence or history of any bleeding diathesis, irrespective of severity.
• Ongoing infection ≥ Grade 2.
• Patients with any seizure disorder requiring medication.
• Non-healing wound, ulcer, or bone fracture.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bayer: collaborator
• Pfizer: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Serrano C, Leal A, Kuang Y, Morgan JA, Barysauskas CM, Phallen J, Triplett O, Marino-Enriquez A, Wagner AJ, Demetri GD, Velculescu VE, Paweletz CP, Fletcher JA, George S. Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7287-7293. doi: 10.1158/1078-0432.CCR-19-2150. Epub 2019 Aug 30.

  PMID: 31471313 DERIVED

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Sunitinib; regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Suzanne George
• Organization: DFCI

Suzanne_George@dfci.harvard.edu

617-632-5204

Study Officials

• Suzanne George, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: Principal Investigator

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 16, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: May 1, 2021
• Last Updated: June 14, 2021
• Results First Posted: September 12, 2019

Record last verified: 2021-05

Locations

US (1)