Trial Outcomes & Findings for Understanding Mechanisms of Acquired Resistance to BIBW2992 (NCT NCT01074177)

NCT ID: NCT01074177

Last Updated: 2018-03-09

Results Overview

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 24 participants
• Primary outcome timeframe: At the time of disease progression (median duration of 11.4 months from start of treatment)
• Results posted on: 2018-03-09

Participant Flow

Participant milestones

Measure	BIBW 2992 BIBW 2992: Taken orally once a day
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	BIBW 2992 n=24 Participants BIBW 2992: Taken orally once a day
Age, Continuous	57 years n=24 Participants
Sex: Female, Male Female	18 Participants n=24 Participants
Sex: Female, Male Male	6 Participants n=24 Participants
Region of Enrollment United States	24 Participants n=24 Participants
Brain Metastasis Present Yes	11 Participants n=24 Participants
Brain Metastasis Present No	13 Participants n=24 Participants
Prior Chemotherapy Yes	6 Participants n=24 Participants
Prior Chemotherapy No	18 Participants n=24 Participants
EGFR Mutation Exon 19 deletion	10 Participants n=24 Participants
EGFR Mutation L858R	8 Participants n=24 Participants
EGFR Mutation Exon 20 insertion	3 Participants n=24 Participants
EGFR Mutation G719A	2 Participants n=24 Participants
EGFR Mutation S768I	1 Participants n=24 Participants

PRIMARY outcome

Timeframe: At the time of disease progression (median duration of 11.4 months from start of treatment)

Population: The 14 participants that experienced disease progression and were also eligible to be biopsied.

Outcome measures

Measure	BIBW 2992 n=14 Participants BIBW 2992: Taken orally once a day
Number of Participants That Have a T790M Mutation on Their Progression Biopsy.	4 Participants

SECONDARY outcome

Timeframe: Baseline and then after the end of every two 28 day cycles until treatment is discontinued; median duration of followup of 19.3 months

The number of participants with either a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

• CR: Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to < 10 mm
• PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	BIBW 2992 n=24 Participants BIBW 2992: Taken orally once a day
Response Rate Complete Response	0 participants
Response Rate Partial Response	14 participants

SECONDARY outcome

Timeframe: start of treatment, at the time of disease progression, time of death

The progression-free and overall survival times. Overall survival is measured from the start of treatment until the time of death or until the participant is lost to follow-up. Progression free survival is measured from the start of treatment until the time of progression, death, or until the participant is lost to follow-up (whichever occurs first). Progression is defined as having at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study with at least a 5 mm absolute increase in the sum of all lesions. The appearance of one or more new lesions denotes disease progression.

Outcome measures

Measure	BIBW 2992 n=24 Participants BIBW 2992: Taken orally once a day
Median Progression-free and Overall Survival Progression Free Survival	11.4 Months Interval 5.9 to 13.7
Median Progression-free and Overall Survival Overall Survival	20.8 Months Interval 15.1 to 40.5

SECONDARY outcome

Timeframe: 7 days post biopsy and ≥ 30 days post-biopsy

The number of participants with biopsy complications from repeat tumor biopsies taken following disease progression. Biopsy complications are any adverse events considered to be potentially related to the biopsy.

Outcome measures

Measure	BIBW 2992 n=24 Participants BIBW 2992: Taken orally once a day
Number of Participants With Biopsy Complications From Repeat Tumor Biopsies	0 Participants

Adverse Events

BIBW 2992

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	BIBW 2992 n=24 participants at risk BIBW 2992: Taken orally once a day
Investigations INR Increased	4.2% 1/24 • Number of events 1 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Muco/stomatitis by exam- oral cavity	4.2% 1/24 • Number of events 1 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Nervous system disorders Seizure	4.2% 1/24 • Number of events 1 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory-other	4.2% 1/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).

Other adverse events

Measure	BIBW 2992 n=24 participants at risk BIBW 2992: Taken orally once a day
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Blood and lymphatic system disorders Hemoglobin	16.7% 4/24 • Number of events 13 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Vascular disorders Hypertension	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
General disorders Fatigue	25.0% 6/24 • Number of events 6 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Psychiatric disorders Insomnia	37.5% 9/24 • Number of events 19 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Investigations Weight loss	20.8% 5/24 • Number of events 6 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Skin and subcutaneous tissue disorders Dry skin	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Skin and subcutaneous tissue disorders Alopecia	25.0% 6/24 • Number of events 13 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Skin and subcutaneous tissue disorders Nail changes	20.8% 5/24 • Number of events 6 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Skin and subcutaneous tissue disorders Rash: acne/acneiform	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Skin and subcutaneous tissue disorders Skin-other	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Metabolism and nutrition disorders Anorexia	25.0% 6/24 • Number of events 6 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Constipation	37.5% 9/24 • Number of events 9 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Metabolism and nutrition disorders Dehydration	12.5% 3/24 • Number of events 4 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Diarrhea w/o prior colostomy	16.7% 4/24 • Number of events 4 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Dry mouth	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Dysphagia	83.3% 20/24 • Number of events 45 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Dyspepsia	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	20.8% 5/24 • Number of events 6 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Nausea	33.3% 8/24 • Number of events 8 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Taste disturbance	29.2% 7/24 • Number of events 7 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Vomiting	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders GI-other	33.3% 8/24 • Number of events 10 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Infections and infestations Infection Gr0-2 neut, oral cavity	54.2% 13/24 • Number of events 16 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Infections and infestations Infection Gr0-2 neut, skin	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Infections and infestations Infection Gr0-2 neut, ungual	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Infections and infestations Infection Gr0-2 neut, upper airway	8.3% 2/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Infections and infestations Infection Gr0-2 neut, urinary tract	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Infections and infestations Infection Gr0-2 neut, vagina	25.0% 6/24 • Number of events 8 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Investigations Alkaline phosphatase	29.2% 7/24 • Number of events 7 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Investigations ALT, SGPT	12.5% 3/24 • Number of events 7 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Investigations AST, SGOT	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Metabolism and nutrition disorders Hypercalcemia	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Investigations Creatinine	29.2% 7/24 • Number of events 27 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Metabolism and nutrition disorders Hypokalemia	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Investigations Hyponatremia	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Metabolism and nutrition disorders Metabolic/Laboratory-other	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Musculoskeletal and connective tissue disorders Musculoskeletal/soft tissue-other	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Nervous system disorders Dizziness	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Psychiatric disorders Anxiety	12.5% 3/24 • Number of events 4 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Psychiatric disorders Depression	50.0% 12/24 • Number of events 16 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Nervous system disorders Neurologic-other	25.0% 6/24 • Number of events 15 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Eye disorders Dry eye syndrome	16.7% 4/24 • Number of events 4 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Gastrointestinal disorders Abdomen, pain	25.0% 6/24 • Number of events 7 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Musculoskeletal and connective tissue disorders Back, pain	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
General disorders Chest wall, pain	45.8% 11/24 • Number of events 19 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
General disorders Chest/thoracic pain NOS	12.5% 3/24 • Number of events 3 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Musculoskeletal and connective tissue disorders Extremity-limb, pain	29.2% 7/24 • Number of events 8 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Nervous system disorders Head/headache	87.5% 21/24 • Number of events 40 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Musculoskeletal and connective tissue disorders Joint, pain	8.3% 2/24 • Number of events 2 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Respiratory, thoracic and mediastinal disorders Cough	29.2% 7/24 • Number of events 7 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Respiratory, thoracic and mediastinal disorders Dyspnea	25.0% 6/24 • Number of events 6 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reaction	20.8% 5/24 • Number of events 5 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).
Renal and urinary disorders Renal/GU-other	16.7% 4/24 • Number of events 4 • From the start of treatment until 30 days after last dose was received. Treatment continued until the participant had disease progression, experienced unacceptable toxicity, died, was lost to follow-up, or until the physician decided it was in their best interest to stop treatment (median duration of approximately 11 months).

Additional Information

Lecia Van Damn Sequist

Massachusetts General Hospital

Phone: 617-724-4000

Email: lvsequist@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place