Selumetinib in Combination With Gefitinib in NSCLC Patients

NCT02025114 | Completed Phase 1 DMC

• 1 other identifier: 201312070MIPC
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, non-randomized, multicenter phase Ib/II study, which is composed of a phase Ib dose escalation part and a phase II dose expansion part. Patients will receive selumetinib in combination with gefitinib 250mg daily. This study will enroll EGFR-mutated NSCLC patients who have developed acquired resistance to EGFR TKI treatment.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

NSCLC, EGFR mutation

Outcome Measures

Primary Outcomes (1)

• To determine the MTD and/or RP2D

  Frequency and characteristics of DLTs to the selumetinib and gefitinib combination using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0. (an expected average of 18 weeks) If one patient experiences a DLT in a group of 3 or more evaluable patients, then the cohort will be expanded to include 6 evaluable patients. If only one DLT is observed in the complete cohort of 6 evaluable patients, then dose escalation may occur.

  an expected average of 18 weeks

Secondary Outcomes (1)

• Overall Response Rate (ORR)

  Patients will be followed up for 2 years(post disease progression)

Study Arms (1)

Capsule

EXPERIMENTAL

The starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID).

Drug: selumetinib

Interventions

selumetinib DRUG

The starting dose of selumetinib in combination with the standard dose of gefitinib (250mg QD) on a continuous dosing schedule will be 50mg QD. Total 3 doses of selumetinib will be tested (50mg QD, 50mg BID and 75mg BID).

Capsule

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained prior to any screening procedures.
• ≥20 years of age.
• Must have discontinued any previous anti-cancer and investigational therapy (excluding EGFR TKI) for at least 28 days or radiotherapy ≥14 days before study treatment administration, and must have recovered to Grade 1 from the adverse effects of such treatment before starting study treatment.
• Life expectancy ≥3months.
• ECOG performance status: 0-1.
• Female patients of child-bearing potential should have a negative pregnancy test.
• Required baseline laboratory status:
• (1) Hemoglobin\>9g/dL. (2) Platelet count≥100x109/L. (3) Absolute neutrophil count (ANC)≥1.5x109/L without growth factor support. (4) Total bilirubin 1.5x upper limit of normal (ULN). (5) AST/SGOT and/or ALT/SGPT 2.5x ULN. (6) Serum creatinine clearance \>50 ml/min, by either Cockcroft-Gault formula or by 24-hour urine collection analysis.
• \. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
• \. In phase Ib part, lung cancer patients with disease progression after EGFR TKI and at least one line of chemotherapy. If less than 70 years of age, a platinum-based regimen must be included.
• \. In phase II part, patients must be willing to perform a re-biopsy of the tumor at the time of study entrance and meet definition of acquired resistance criteria of Jackman's as follows:
• (1) Previous treatment with EGFR TKI (gefitinib, erlotinib, afatinib, dacomitinib, AZD9291, or any EGFR TKI under investigation).
• (2) Either or both of the followings:
• A tumor harboring an EGFR mutation known to be associated with drug sensitivity (ie, exon 19 deletion , L858R, L861Q, G719X etc.).
• Objectively clinical benefit from treatment with EGFR TKI as defined by either: Documented partial or complete response (RECIST or WHO) or Significant and durable(≥ 6months) clinical benefit (stable disease as defined by RECIST or WHO) after initiation of EGFR TKI.

You may not qualify if:

• Unable or unwilling to swallow capsules once or twice daily.
• Patients who had discontinued previous gefitinib treatment due to intolerance of side effects (such as diarrhea ≥CTCAE Grade 2, intolerable skin rash, ILD or AST/ALT elevation ≥ CTCAE Grade 3).
• Previous treatment of MEK, Ras, or Raf inhibitors or history of hypersensitivity to selumetinib, or any excipient agents.
• Symptomatic CNS metastases which are neurologically unstable or requiring increasing doses of steroids to control the CNS condition.
• Radiation therapy within 4 weeks prior to the first dose of study drug or limited field radiotherapy within 2 weeks prior to the start of study treatment. Any persistent side effect of prior radiotherapy must be resolved to Grade 1 prior to the first dose of study treatment.
• Any unresolved toxicity from previous anticancer therapy \> Grade 1.
• Currently receiving any prohibited medications including vitamins supplements, and herbal supplements. Refer to Table 6.5 for a list of excluded medication.
• Unable to undergo an MRI or contrast CT procedures.
• Active HBV or HCV infection, HBV carrier can be enrolled if HBV DNA titer is low under antiviral treatment.
• Known history of HIV seropositivity. HIV testing is not required as part of this study.
• Undergone a bone marrow or solid organ transplant.
• Another malignancy diagnosed or treated within 5 years, except carcinoma in situ or skin cancer.
• Major surgery within 4 weeks prior to initiating study treatment, excluding the placement of vascular access.
• Cardiac conditions as follows:
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Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (3)

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Department of Oncology, National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chih-Hsin Yang, MD, PhD

  National Taiwan University Hospital

  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: SPONSOR

Study Record Dates

• First Submitted: December 24, 2013
• First Posted: December 31, 2013
• Study Start: September 1, 2014
• Primary Completion: March 8, 2018
• Study Completion: March 8, 2018
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

TW (3)