Study to Determine the Maximum Tolerated Dose of BIBW 2992 (Afatinib) When Combined With Cisplatin/Paclitaxel or Cisplatin/5-FU in Patients With Advanced Solid Tumours

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00716417
Recruitment Status : Completed
First Posted : July 16, 2008
Results First Posted : October 16, 2013
Last Update Posted : June 9, 2014
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

Study to determine the maximum tolerated dose of BIBW 2992 when combined with backbone chemotherapies consisting in cisplatin plus paclitaxel or cisplatin plus 5 FU.

The overall safety, the pharmacokinetics and the anti-tumour efficacy will also be assessed.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BIBW 2992 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Open Label Study to Assess the Safety, Tolerability and Pharmacokinetics of Continuous Dosing With BIBW 2992 Combined With Two Different Regimens of Backbone Chemotherapy: Cisplatin Combined With 5 Fluorouracil and Cisplatin Combined With Paclitaxel in Patients With Advanced Solid Tumors.
Study Start Date : July 2008
Actual Primary Completion Date : July 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: A. BIBW 2992-cisplatin-paclitaxel
daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-paclitaxel
Drug: BIBW 2992
low to high dose, daily

Experimental: B. BIBW 2992-cisplatin-5FU
daily oral dose of BIBW 2992 combined with 3-weekly infusion of cisplatin-5FU
Drug: BIBW 2992
In each arm, BIBW 2992 dose will be escalated to determine MTD. Starting dose will be 20mg daily followed by 40 mg (with the option of an intermediary dose of 30 mg) then 50mg daily. Dose escalation will stop at 50 mg. No intra patient dose escalation.

Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities (DLT) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD) [ Time Frame: 21 days ]
    Number of participants with DLT in the first cycle (21 days) for the determination of the MTD.

  2. Maximum Tolerated Dose (MTD) for Regimen A and Regimen B [ Time Frame: 21 days ]
    The MTD was determined using a standard 3 +3 dose escalation cohort design. The sample size and the number of patients who receive each dose in this design depends on the frequency of DLT at each dose level in cycle 1.

Secondary Outcome Measures :
  1. Number of Patients With Objective Response [ Time Frame: Tumor assessment were performed at screening and every 2nd cycle until end of follow up (=end of treatment + 30 days +/- 7 days) ]
    Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.0. Objective response is defined as complete response (CR) and partial response (PR).

  2. Maximum Concentration of Afatinib in Plasma at Steady State (Cmax,ss) [ Time Frame: 0.05hours (h) before administration and 1h, 2h, 2h 55 minutes (min), 4h, 4h 30min, 5h, 6h, 8h, 10h, 24h, 48h, 216h, 480h after administration ]
    Cmax,ss represents the maximum concentration of afatinib in plasma at steady state

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Patients with histologically or cytologically confirmed diagnosis of non resectable and / or metastatic cancer, preferably squamous cell carcinomas of head and neck, oesophagus, lung or cervix
  2. Indication for a standard treatment with either cisplatin plus paclitaxel or cisplatin plus 5 FU as judged by the investigator
  3. Age 18 years or older.
  4. Life expectancy of at least three (3) months.
  5. Written informed consent that is consistent with ICH-GCP guidelines.
  6. Eastern Cooperative Oncology Group (ECOG) performance score less or equal 2.
  7. Patients must have recovered from any therapy-related toxicity from previous chemo-, hormone-, immuno-, or radiotherapies.
  8. Patients recovered from previous surgery.

Exclusion criteria:

  1. Active infectious disease.
  2. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea.
  3. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
  4. 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 four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks and no requirement for steroids or anti-epileptic therapy.
  5. Cardiac left ventricular function with resting ejection fraction less than 50%
  6. Absolute neutrophil count (ANC) less than 1500 / mm3.
  7. Platelets count less than 100 000/mm3.
  8. Bilirubin more than 1.5 x upper limit of institutional norm.
  9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) more than 3 x upper limit of institutional norm.
  10. Serum creatinine more than 1.5 x upper limit of institutional norm.
  11. Women and men sexually active and unwilling to use a medically acceptable method of contraception.
  12. Pregnancy or breast-feeding.
  13. Treatment with other investigational drugs; chemotherapy, immunotherapy, or radiotherapy or participation in another clinical study with anti-cancer therapy within the past 4 weeks before start of therapy or concomitantly with this study.
  14. Treatment with an EGFR- or HER2 inhibiting drug within the past four weeks before start of therapy or concomitantly with this study (2 weeks for trastuzumab).
  15. Patients unable to comply with the protocol.
  16. Active alcohol or drug abuse.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00716417

1200.37.3202 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1200.37.3201 Boehringer Ingelheim Investigational Site
Edegem, Belgium
1200.37.3203 Boehringer Ingelheim Investigational Site
Gent, Belgium
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Responsible Party: Boehringer Ingelheim Identifier: NCT00716417     History of Changes
Other Study ID Numbers: 1200.37
2008-002613-43 ( EudraCT Number: EudraCT )
First Posted: July 16, 2008    Key Record Dates
Results First Posted: October 16, 2013
Last Update Posted: June 9, 2014
Last Verified: August 2013

Additional relevant MeSH terms:
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action