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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00716417
First received: July 15, 2008
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Neoplasms
Drug: BIBW 2992
Drug: BIBW 2992
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Masking: 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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:
  • To define MTDA and MTDB of BIBW 2992 when combined with cisplatin/paclitaxel or cisplatin/5-FU as assessed during the first cycle. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and intensity of adverse events according to Common Toxicity Criteria (CTCAE v.3.0) associated with increasing doses of BIBW 2992 in combination with I.V. administration of cisplatin with either paclitaxel or 5-FU. [ Time Frame: from 1st treatment until EOT ] [ Designated as safety issue: No ]
  • Pharmacokinetic and pharmacodynamic parameters of BIBW 2992 in combination with I.V. cisplatin and paclitaxel or cisplatin and 5-FU. [ Time Frame: from 1st treatment until EOT ] [ Designated as safety issue: No ]
  • Objective tumour response based on RECIST criteria. [ Time Frame: from 1st treatment until EOT ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: July 2008
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00716417

Locations
Belgium
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 Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00716417     History of Changes
Other Study ID Numbers: 1200.37, 2008-002613-43
Study First Received: July 15, 2008
Last Updated: January 19, 2012
Health Authority: Belgium: Federal Agency for Medicines and Health Products

Additional relevant MeSH terms:
Neoplasms
Cisplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 23, 2013