Phase I Trial Evaluating Safety and Tolerability of the Irreversible Epidermal Growth Factor Receptor Inhibitor Afatinib (BIBW 2992) in Combination With the SRC Kinase Inhibitor Dasatinib for Patients With Non-small Cell Lung Cancer (NSCLC)
Overview
- Phase
- Phase 1
- Intervention
- Dasatinib - 1A
- Conditions
- Lung Cancer
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The purpose of this study is to:
- Find out if the study drugs Afatinib and Dasatinib can be safely given together to patients with lung cancer
- Learn how these two drugs work in cancer cells when they are combined
- Learn more about the side effects of these two drugs when combined
- Find the highest doses of the study drugs Afatinib and Dasatinib that can be given safely without causing serious side effects
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically or cytologically documented Stage IIIB/IV non-small cell lung cancer, or unresectable recurrent disease following locoregional treatment.
- •For Phase 1B Extension Only:
- •Either or both of the following: A tumor which harbors an activating Epidermal Growth Factor Receptor (EGFR) - mutation; History of objective response, or stable disease for at least 6 months, after treatment with erlotinib, afatinib, or gefitinib.
- •Either or both of the following: Progression or recurrence of disease after receiving prior continuous gefitinib, afatinib, or erlotinib; A tumor known to harbor a de novo T790M mutation, which is known to confer EGFR TKI resistance.
- •Participants are allowed to have received systemic chemotherapy or investigational therapy in the intervening period prior to trial enrollment
- •Capable of giving written informed consent.
- •Evaluable disease, as follows: For Phase 1A Dose Escalation: Have the presence of any evaluable disease, including bone metastases, effusion, or cystic metastases. For Phase 1B Extension Only: Have progressive and measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1).
- •Reproductive potential must be either terminated (by surgery, radiation, or menopause) or attenuated by the use of an approved contraceptive method during and for 3 to 6 months following the study.
- •Participant agrees that IV bisphosphonates will be withheld during the first 8 weeks of dasatinib therapy due to risk of hypocalcemia.
- •Have recovered from prior drug-related toxicity to Grade ≤ 1 Common Terminology Criteria for Adverse Events (CTCAE) v4, within 21 days of initiation of on-study treatment.
Exclusion Criteria
- •Have previously completed or withdrawn from this study or any other study investigating dasatinib. Prior treatment with other tyrosine kinases, including afatinib, is acceptable.
- •Prior recent systemic or investigational therapy within 21 days of initiation of study treatment. An exception is that epidermal growth factor receptor (EGFR) inhibitor may be continued up until 3 days of initiation of study treatment.
- •Women who are pregnant or breastfeeding. Women of childbearing potential must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment.
- •Patients with documented central nervous system or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis and no longer require corticosteroids.
- •Patients with disease progression in the central nervous system (CNS) only.
- •Serious concomitant disorder, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the principal investigator).
- •Uncorrected severe electrolyte disorder, including severe potassium (\<3.0 mEq/L) or magnesium ( \< 1.0 mEq/L) deficiency.
- •Any gastrointestinal disorder with diarrhea as a major symptom, such as Crohn's, or pre-existing chronic diarrhea Common Toxicity Criteria (CTC) Grade ≥ 2 of any etiology. Included are malabsorption disorders that in the opinion of the study physician may affect absorption of either afatinib or dasatinib.
- •Prior major surgery or radiation therapy within 14 days of initiation of treatment.
- •Electrocardiogram (ECG) abnormalities indicative of arrhythmia (at the discretion of the investigator).
Arms & Interventions
Dose Escalation and Dose Expansion
Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end. Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B.
Intervention: Dasatinib - 1A
Dose Escalation and Dose Expansion
Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end. Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B.
Intervention: Afatinib - 1A
Dose Escalation and Dose Expansion
Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end. Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B.
Intervention: Dasatinib - 1B
Dose Escalation and Dose Expansion
Dose escalation followed by dose expansion. Escalation cohort: Afatinib and Dasatinib. This study is divided into two parts. The first 8 - 18 people will be entered in the first part, called Phase 1A. Then this part will end. Expansion cohort:: Afatinib and Dasatinib. The next 20 people will enter into the second part, called Phase 1B.
Intervention: Afatinib - 1B
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of Afatinib (BIBW 2992) in Combination With Dasatinib
Time Frame: Up to 6 Months
The MTD for this combined treatment will be defined as either: 1. The highest dosage cohort in which six patients had been treated and there were less than two dose limiting toxicities (DLTs) or, 2. Afatinib at the highest tolerated dose investigated (40 mg by mouth \[PO\] daily) plus dasatinib at the highest tolerated dose investigated (cohort 3, 140 mg PO daily).
Secondary Outcomes
- Number of Participants With Objective Response(Up to 6 Months)
- Median Progression Free Survival(Up to 6 Months)