A Phase I Dose Escalation Trial of Afatinib Plus Gemcitabine or Plus Docetaxel

NCT01251653 | Completed Results

• 2 other identifiers: 1200.932010-020560-37
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 3

Brief Summary

To establish the maximum tolerated dose (MTD) of oral afatinib (BIBW2992) given in combination with gemcitabine or docetaxel in patients with relapsed or refractory tumors. To assess the safety of the combination. To investigate the PK characteristics of docetaxel or gemcitabine and of oral afatinib (BIBW2992) in the tested treatment schedule. To assess antitumor activity.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).

  DLT was based on following criterions: 1. Grade 4 uncomplicated (not associated with fever \>38.5° C (Celsius)) neutropenia for ≥7 days. 2. Grade 3 or 4 neutropenia concomitant with fever \>38.5º C or Grade ≥3 infection. 3. Platelet count of \<25x 10\^9/L or \<50x 10\^9/L with bleeding requiring whole blood transfusion. 4. Grade ≥3 non-haematological toxicity (except untreated nausea, untreated vomiting, or untreated diarrhoea). 5. Grade ≥2 decrease in cardiac left ventricular function. 6. Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria, or a newly developed decrease in glomerular filtration rate. Toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0

  3 weeks

Secondary Outcomes (19)

• The Incidence and Intensity of AEs With Grading According to CTCAE.

  From first drug administration until 28 days after last drug administration, up to 717 days.

• Best Overall Response According to RECIST v1.1 Criteria

  From first drug administration until 28 days after last drug administration, up to 717 days.

• Disease Control According to RECIST v1.1

  From first drug administration until 28 days after last drug administration, up to 717 days.

• Objective Response According to RECIST v1.1

  From first drug administration until 28 days after last drug administration, up to 717 days.

• Time to Objective Response According to RECIST v1.1

  6 weeks, 12 weeks and 24 weeks

Study Arms (2)

Afatinib and docetaxel

Drug: Afatinib; Drug: docetaxel

Afatinib and gemcitabine

Drug: Afatinib; Drug: gemcitabine

Interventions

Afatinib DRUG

Maximum Tolerated Dose of Afatinib in combination with gemcitabine

Afatinib and docetaxel

docetaxel DRUG

Maximum Tolerated Dose of Afatinib in combination with docetaxel

Afatinib and docetaxel

gemcitabine DRUG

Maximum Tolerated Dose of Afatinib in combination with gemcitabine

Afatinib and gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

solid tumors

You may qualify if:

• \. histologically or cytologically confirmed diagnosis of any advanced or metastatic relapsed or refractory solid tumor.

You may not qualify if:

• Active brain metastases
• Patients with known pre-existing interstitial lung disease

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

1200.93.33002 Boehringer Ingelheim Investigational Site

Dijon, France

Location

1200.93.33001 Boehringer Ingelheim Investigational Site

Saint-Herblain, France

Location

1200.93.33003 Boehringer Ingelheim Investigational Site

Toulouse, France

Location

Related Publications (1)

• Hiret S, Isambert N, Gomez-Roca C, Bennouna J, Sassi M, de Mont-Serrat H, Fan J, Schnell D, Delord JP. Phase I dose-escalation trial of afatinib, an irreversible ErbB family blocker, in combination with gemcitabine or docetaxel in patients with relapsed or refractory solid tumors. Invest New Drugs. 2018 Dec;36(6):1044-1059. doi: 10.1007/s10637-018-0601-1. Epub 2018 May 29.

  PMID: 29808308 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Pharmacokinetic samples

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib; Docetaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 2, 2010
• Study Start: November 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: May 30, 2016
• Results First Posted: May 30, 2016

Record last verified: 2016-04

Locations

FR (3)