Dasatinib and Osimertinib (AZD9291) in Advanced Non-Small Cell Lung Cancer With EGFR Mutations

Part of paid clinical trials in Washington D.C., District of Columbia.

Sponsor
Chul Kim
Study ID
NCT02954523
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

  • EGFR Gene Mutation
  • Nonsmall Cell Lung Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Dasatinib — DRUG
    oral every day
  • Osimertinib — DRUG
    oral every day

Study Details

This is a study for patients with advanced non-small cell lung cancer with changes to their cancer cells called EGFR mutations. Mutated EGFR is important in the growth of cancer cells. Medical studies have shown that patients with EGFR mutation-positive lung cancer gain more benefit from targeted therapy drugs such as EGFR inhibitors than with standard chemotherapy. However, a significant proportion of patients carrying these sensitizing mutations do not respond well to the first-generation EGFR-TKIs (erlotinib and gefitinib), indicating the existence of intrinsic resistance mechanisms. Moreover, despite initial response to EGFR-TKIs, acquired resistance is inevitable in all patients. The investigators have recently shown that Cripto-1 overexpression in EGFR mutant NSCLC contributes to the intrinsic resistance to EGFR-TKIs through activation of the SRC oncogene. They have also shown that a combination of an EGFR-TKI (both erlotinib and osimertinib) and a Src inhibitor are synergistic in Cripto-1 overexpressing tumors in the laboratory. This study will be testing a combination of two drugs, dasatinib and osimertinib, to overcome resistance to EGFR-TKIs. Osimertinib (AZD9291) is a third-generation EGFR-TKI, which selectively blocks the activity of EGFR mutants, but spares that of wild type. The advantage of using osimertinib is that it inhibits not only the sensitizing EGFR mutations, but also the T790M mutant, which is the most common mechanism of acquired resistance. Dasatinib is a potent, orally available ABL1/SRC TKI, approved for the treatment of chronic myeloid leukemia (CML) in first-line and in patients with imatinib-resistant disease or intolerant, and is being actively studied in patients with advanced solid tumors. The first part of the study will involve finding the highest dose of dasatinib that can be given with osimertinib without causing severe side effects, finding out the side effects seen by giving dasatinib at different dose levels with osimertinib, and measuring the levels of dasatinib and osimertinib in blood at different dose levels. The second part will determine the effects of the combination of dasatinib and osimertinib and determine if the amount of Cripto-1 protein in your tumor or blood makes you more likely to have a good response to the combination of dasatinib and osimertinib.

Key Dates

Start date
Oct 31, 2016
Status verified
Jul 2024
Primary completion
Aug 31, 2018
Completion
Mar 3, 2023

Study Design

Enrollment
10 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase I- Dasatanib Dose Level 1
    Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at up to 4 dose levels. Level 1 (the starting dose - 50 mg twice daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive.
  • Experimental: Phase I- Dasatanib Dose Level 2
    Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at up to 4 dose levels. Level 2 (70 mg twice daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive.
  • Experimental: Phase I- Dasatanib Dose Level -1
    Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule. Dasatinib is taken orally and will be given at up to 4 dose levels. Level -1 (70 mg once daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive.
  • Experimental: Phase I- Dasatanib Dose Level -2
    Osimertinib (AZD9291) will be given at a 80mg/day dose taken orally across all levels of the dose escalation schedule.d Dasatinib is taken orally and will be given at up to 4 dose levels. Level -2 (50 mg once daily). Dose escalation will only include 2 dose levels (Levels 1 and 2); in addition there will be 2 dose levels below the starting dose level if dose reductions are necessary (Levels -1 and -2). There is no limit to the number of cycles a patient can receive.
  • Experimental: Phase II- Maximum tolerated dose
    The phase II portion of the study will use the maximum tolerated dose of dasatinib determined in the phase I portion. Osimertinib (AZD9291) will be given at the same 80mg dose as the phase I portion. There is no limit to the number of cycles a patient can receive.

Primary Outcome Measure

Phase I : Number of Patients With Drug-related Adverse Events as Assessed by CTCAEv4.0 [ Time Frame: Cycle 1 (28 day cycle) ]

Locations (2)

FacilityCityStateZIPSite coordinators
Georgetown Lombardi Comprehensive Cancer CenterWashington D.C.District of Columbia20007-
John Theurer Cacner Center at Hackensack University Medical CenterHackensackNew Jersey07601-

Find similar trials in Washington D.C., DC

By research site
Georgetown Lombardi Comprehensive Cancer Center· Washington D.C., DCJohn Theurer Cacner Center at Hackensack University Medical Center· Hackensack, NJ

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