The primairy objective of the trial is to determine the efficacy of BIBW 2992 plus weekly paclitaxel compared to the investigators choise of chemotherapy alone in patients with NSCLC stage IIIb or IV progressing after experiencing a benefit from…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Overall survival time from the day of randomization until death for patients
randomized to either BIBW 2992/ paclitaxel combination therapy or comparator
chemotherapy.
Secondary outcome
Secondary endpoints:
1: progression free survival as determined by RECIST1.1(response evaluation
criteria in solid tumours), separately for Part A and Part B
2: Clinical benefit rate at 3 month defined as the progression free survival
rate at 3 month, separately for Part A and Part B
3: Objective response rate (CR {complete response} PR {partial response}) of
BIBW 2992 monotherapy according to RECIST 1.1
4: Objective response rate (CR or PR) of BIBW 2992/ Paclitaxel combination
therapy and comparator therapy in Part B after progression in Part A according
to RECIST 1.1
5: Time to objective response, separately for Part A and Part B
6: HRQOL defined as time to deterioration fro the three symptoms cough,
dyspnoe, and pain, measured using the European Organization for Research and
Treatment of Cancer questionaires (QLO-LC13 and QLQ C30)
Background summary
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death
globally, with an estimated one million new cases diagnosed and 880.000 death
each year. The prognosis for advanced stage disease has not changed
significantly in the past 20 years. With n overall 5-years survival rate of
only 15%, the treatment of this disease remains a major clinical challenge.
In patients with advanced NSCLC (stage IIIb pleural effusion or stage IV
metastatic disease)systemic chemotherapy is considered the first treatment of
choise, prolonging the median survival and palliating tumor-related symptoms.
Despite the high levels of epidermal growth factor receptor(EGFR)
overexpression in the tumoours for the majority pf patients with NSCLC, recent
clinical experiences with specific EGFR-tyrosine kinase inhibitors (TKI's) have
demonstrated tumour regression in only 10% to 15% of unselevted NSCLC patients.
Further investigations in patients who responded to TKI therapy have indicated
that the sensitivity to therapy may be correlated with the presence of EGFR
activating mutations.
BIBW 2992 is a second generation TKI which binds irreversable to EGFR and HER2
and is thought to have potential benefit over the first generation TKI's such
as erlotinib and gefitinib.
One of the reasons for the potential benefit is that BIBW2992 may have activity
against EGFR-tyrosine kinases with mutations which are resistant to the first
generation TKI's. Additionally, the irriversible binding may confer more
prolonged activity, further delaying tumour progression when compared to
reversible TKI's.
Study objective
The primairy objective of the trial is to determine the efficacy of BIBW 2992
plus weekly paclitaxel compared to the investigators choise of chemotherapy
alone in patients with NSCLC stage IIIb or IV progressing after experiencing a
benefit from BIBW 2992 monotherapy.
Additional information on safety and the health related quality of life (HRQOL)
will be collected. Patients on both arms will receive the best supportive care
in addition to study treatment.
Randomized patients in the trial will be treated and followed until death,
study termination or are lost to follow up.
Study design
Phase III, randomized, open label study
Intervention
Part A:
BIBW 2992 monotherapy
Part B:
arm 1: BIBW 2992 plus Paclitaxel
arm 2: investigators choise of chemotherapy
Study burden and risks
During screening the participating patients will have a complete physical
examination, an ECG, an echo or Muga scan( to check the ejection fraction),
blood will be drawn( haematology and biochemistry) and a CT or MRI will be
done for tumour evaluation.
During the following cycli of the visits 1, 2,and 3 (every 28 days) the patient
will come twice per cycle to the clinic.
From cycle 4, the vsits will occur every 28 days.
Every 6 weeks the CT or MRI to establish the tumour response will be done
Comeniusstraat 6
1817 MS
NL
Comeniusstraat 6
1817 MS
NL
Listed location countries
Age
Inclusion criteria
In study part A:
1: Patients with confirmed diagnosis of NSCLC stage IIIb or stage IV who have failed treatment with erlotinib or gefitinib.
2: patients should have received and failed at least one line of cytotoxic chemotherapy, including a platinum-based regimen in patients eligible for platinum-based therapy for advanced or metastatic disease, however the following patients are exempted:
a) patients with known EGFR mutation shown by accepted methods after therapy with reversible TKI's are eligible without prior chemotherapy, OR
b) patients with clinical benefit to erlotinib or gefitinib for 6 month or more and than experience progression of the disease are eligible without prior chemotherapy
3: Eastern Cooperative Oncology Group (ECOG, R01-0787) score 0,1,or 2.
4: Patients with at least one tumour lesion measured by MRI or CT scan in at least one dimension with the longest diameter to be recorded equal or larger than 20 mm using conventional techniques or equal or larger than 10 mm using spiral CT scan to RECIST 1.1 (R09-0262)
5: Male and female patients of 18 years or older
6: life expectancy of at least 12 weeks;In study part B:
Clinical benefit (stable disease) for at least 12 weeks in part A of the trial, and than shown progression of the disease according to RECIST 1.1 criteria.
Exclusion criteria
1.previous treatment with BIBW
2. active brain metastasis
3. history or presence of clinically relevant cardiovasculair abnormalities
4. chemo-, hormone-, or immunotherapy within the past 4 weeks. For pre-treatment with reversible TKI's 2 weeks only.
5. significant or recent acute gastrointestinal disorder with diarrhea as a major symptom at baseline
6. other life-threatening illness or organ dysfunction, or other malignancies that either might compromise the patients safety or requiers therapy
7. radiotherapy within the past 2 weeks prior to treatment with the trial drug
8. history or presence of clinically relevant cardiovasculair abnormalities as defined in the exclusion criteria.
9. prior treatment with antracyclines with a cumulative dose of >= 400mg/m².
10. clinically significant abnormal lab functions as defined in the protocol
11. pregnant women, breastfeeding women or women of childbearing potential unwilling to use a medically acceptable method of contraception
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014563-39-NL |
| CCMO | NL30914.100.10 |