Trial Exploring Afatinib (BIBW 2992) + Paclitaxel (Part A), Afatinib + Paclitaxel + Bevacizumab (Part B), Afatinib + Carboplatin (Part C) and Afatinib+ Paclitaxel +Carboplatin(Part D) in Patients With Advanced Solid Tumours

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00809133
First received: December 16, 2008
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

The main purpose of this study is to assess the optimum dose of the following medications when they are given together:

  • BIBW 2992 and paclitaxel (Taxol)
  • BIBW 2992 and paclitaxel and bevacizumab (Avastin)
  • BIBW 2992 and carboplatin
  • BIBW 2992 and paclitaxel and carboplatin The effect of the different drug combinations will also be assessed.

Condition Intervention Phase
Neoplasms
Drug: Paclitaxel
Drug: Carboplatin
Drug: BIBW 2992
Drug: BIBW2992
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Open Label Trial of Continuous Dosing With BIBW 2992 Combined With Paclitaxel and BIBW 2992 Combined With Paclitaxel and Bevacizumab, BIBW 2992 Combined With Carboplatin and BIBW 2992 Combined With Paclitaxel and Carboplatin in Patients With Advanced Solid Tumours

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • To define the MTD of BIBW 2992 in combination with carboplatin [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • To define the MTD of BIBW 2992 when added to standard Paclitaxel/carboplatin combination therapy. [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • To define the MTD of BIBW 2992 in combination with Paclitaxel. [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • To define the MTD of bevacizumab when added to BIBW 2992 and Paclitaxel. [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and intensity of AE according to Common Toxicity Criteria (CTC v.3) associated with increasing doses of BIBW 2992 [ Time Frame: 12 months in average ] [ Designated as safety issue: No ]
  • Pharmacokinetic characteristics of BIBW 2992, paclitaxel, bevacizumab and carboplatin [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]
  • Objective tumour response [ Time Frame: 12 months in average ] [ Designated as safety issue: No ]
  • Correlation of EGFR, HER2, oestrogen receptor (ER) and progesterone receptor (PrR) immunohistochemical status as based on tumour biopsies (if applicable and available), or excisions obtained prior to this trial, with objective tumour responses. [ Time Frame: 28 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 83
Study Start Date: May 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A
BIBW2992 + Paclitaxel
Drug: BIBW 2992
Escalating dose cohorts
Drug: Paclitaxel
Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.
Experimental: Part B
BIBW2992 + Paclitaxel + Bevacizumab
Drug: Paclitaxel
Part A and B:80mg/m2 given on Day 1, 8 and 15 of 28 Day cycle.
Drug: BIBW2992
MTD dose of part A
Drug: Bevacizumab
Escalating dose Cohorts - 5mg / kg, 7.5mg / kg and 10mg / kg given Day 1 and Day 15 of a 28 days cycle
Experimental: Part C
BIBW2992 + Carboplatin
Drug: Carboplatin
AUC6 given on day 1 of 21 day cycle
Drug: BIBW 2992
Escalating dose cohorts
Experimental: Part D
BIBW2992 +Paclitaxel + Carboplatin
Drug: Carboplatin
AUC6 given on day 1 of 21 day cycle
Drug: Paclitaxel
175mg/m2 given on Day 1 of 21 Day cycle
Drug: BIBW 2992
Escalating dose cohorts

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Male or female patients (patients) with a histologically confirmed diagnosis of malignancy that is now advanced, non-resectable and / or metastatic.
  2. Age 18 years old or older.
  3. Life expectancy of at least 3 months.
  4. Written informed consent that is consistent with ICH-GCP guidelines.
  5. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  6. Patients must have recovered from any previous surgery.
  7. Adequate organ function including the following:
  8. Cardiac left ventricular function with resting ejection fraction greater than or equal to 50%
  9. Absolute neutrophil count of greater than or equal to 1,500/microlitres; greater than 2000/microlitres for carboplatin
  10. Platelets greater than or equal to 100,000/microlitres
  11. Total bilirubin less than or equal to 1.5 mg/dl (<26 micromol /L, SI unit equivalent).
  12. AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal.
  13. Creatinine less than or equal to 1.5 mg/dl (less than or equal to 132 micromol per liter, SI unit equivalent).
  14. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment. Breast feeding mothers will be excluded since these agents may be toxic to infants.

Exclusion criteria:

  1. Active infectious disease
  2. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol
  3. GI tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease.
  4. Significant cardiovascular disease (a history of congestive heart failure requiring therapy, a need for anti-arrhythmic therapy for a ventricular arrhythmia, unstable angina pectoris or myocardial infarction within 6 months prior to trial entry).
  5. Patients who require full-dose anticoagulation.
  6. Patients not completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC less than or equal to Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to 1st trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.
  7. Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least 8 weeks, no history of cerebral oedema or bleeding in the past 8 weeks and no requirement for steroids or anti-epileptic therapy
  8. Persistent Grade 2 or greater neurotoxicity / neuropathy from any cause.
  9. Patients on immunosuppressant therapy or with known HIV infection.
  10. Treatment with any of the following within 4 weeks of starting trial medication, or during the trial, is not permitted: chemo-, immuno-, radio- (small field palliative radiotherapy is allowed provided this does not represent clear disease progression), biological therapies (including trastuzumab), hormone therapy (excluding LHRH agonists in prostate cancer, or bisphosphonates), or treatment with other investigational drugs.
  11. Participation in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial.
  12. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past 4 weeks before start of therapy or concomitantly with this trial.
  13. Patients with known or suspected hypersensitivity to any of the trial drugs, their excipients or similar compounds.
  14. Patients unable to comply with the protocol.
  15. Active alcohol or drug abuse.
  16. Patients with known pre-existing interstitial lung disease

    Additional exclusion criteria for patients recruited to cohorts B:

  17. Patients with known or suspected hypersensitivity to bevacizumab, its excipients or Chinese hamster ovary cell products or other recombinant human or humanised antibodies.
  18. Patients with brain metastases (a brain scan is not required unless the patient shows signs and symptoms of brain metastases and a brain scan is performed to rule out the presence of brain metastases).
  19. Patients with intra-abdominal inflammation .
  20. Major surgery within 4 weeks of starting treatment or any wound(s) deemed by the investigator to pose a significant risk to the patient in the event of delayed healing.
  21. Prior treatment with anthracycline and/or prior radiation to the chest wall ( patients in these categories will only be entered into the study where the investigator deems the benefit to the patient to outweigh the risk).
  22. Patients with any of the following conditions: significant hypertension, significant haemoptysis, known brian metastases, thrombotic or haemorrhagic disorders, INR greater than or equal to 1.5 abnormal PTT, therapeutic anti-coagulation, squamous non small cell lung cancer Additional exclusion criteria for patients recruited to cohorts C and D

    • Patients with severe myelosuppression; i.e. absolute neutrophil count less than 2000/microlitres
    • Patients with renal impairment (creatinine clearance less than 60ml per minute by Cockcroft-Gault equation)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00809133

Locations
United Kingdom
1200.12.4402 Boehringer Ingelheim Investigational Site
London, United Kingdom
1200.12.4401 Boehringer Ingelheim Investigational Site
Sutton, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00809133     History of Changes
Other Study ID Numbers: 1200.12, 2006-005005-55
Study First Received: December 16, 2008
Last Updated: July 9, 2014
Health Authority: Great Britain: MHRA

Additional relevant MeSH terms:
Neoplasms
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014