Trial of Afatinib (BIBW 2992) + Cetuximab in Advanced Solid Tumours

NCT02020577 | Completed Phase 1 Results

• 2 other identifiers: 1200.1222012-005230-10
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 2

Brief Summary

The trial is divided in two parts, Part A and Part B. Part A will involve dose-finding of dose-limiting toxicity (DLT) and MTD in patients with advanced solid tumours. Part B will involve expansion of the MTD to 3 cohorts including non-small cell lung cancer squamous histology, recurrent/ metastatic squamous cell carcinoma of head and neck and other advanced solid tumours (except sarcomas).

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

• MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Afatinib).

  Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with dose limiting toxicity (DLT) during the first treatment cycle (Dose escalation part). The MTD is defined as the highest dose level at which less than 33% of the patients experience DLT in first treatment cycle.

  First 21 days treatment cycle

• Dose Limiting Toxicities During Cycle 1

  Number of Patients With Dose Limiting Toxicity (DLT) Occurring during Cycle 1. The following drug related AEs qualified as DLT: 1\) CTCAE Grade ≥2 decrease in cardiac left ventricular function 2) CTCAE Grade 2 diarrhoea lasting for ≥7 days, despite appropriate use of standard antidiarrheal therapy based on Protocol Amendment 1 dated 22 Oct 2013 3) CTCAE Grade ≥3 diarrhoea despite appropriate use of standard anti-diarrheal therapy for at least 2 days. 4) CTCAE Grade ≥3 nausea and/or vomiting despite appropriate use of standard anti-emetics for at least 3 days 5) CTCAE Grade ≥3 rash despite standard medical management. 6) CTCAE Grade ≥3 fatigue lasting more than 7 days. 7) All other AEs of CTCAE Grade ≥3 (except alopecia and allergic reaction) that led to an interruption of afatinib and/or cetuximab dosing for more than 14 days until recovery to baseline or Grade 1, whichever was higher. 8) CTCAE Grade 4 hypomagnesemia or Grade 3 hypomagnesemia with clinically-significant sequelae

  First 21-day treatment cycle

• MTD of Afatinib in Combination With Cetuximab Based on the Number of Patients With DLTs During the First Treatment Cycle (Cetuximab).

  Maximum Tolerated Dose (MTD) of Afatinib in combination with cetuximab based on the number of patients with DLTs during the first treatment cycle (Dose escalation part).

  First treatment cycle

Secondary Outcomes (6)

• Dose Limiting Toxicities During All Treatment Cycles

  All treatment cycle (each treatment cycle of 21 days)

• Recommended Phase II Dose Based on the Number of Patients With Dose Limiting Toxicity Events (Cetuximab)

  All treatment cycle (each treatment cycle of 21 days)

• Best Overall Response

  Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months

• Objective Response

  Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months

• Disease Control Rate

  Post baseline tumour-imaging was performed at every 6 weeks (in the week preceding the start of Cycles 3, 5, 7, 9, 11, etc.) until EOT; up to 19 months

Study Arms (1)

combination arm

EXPERIMENTAL

Patients to receive afatinib once daily plus weekly cetuximab infusion

Drug: Cetuximab( erbitux®); Drug: Afatinib

Interventions

Cetuximab( erbitux®) DRUG

once per week

combination arm

Afatinib DRUG

once per day

combination arm

Eligibility Criteria

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

You may qualify if:

• Part A only
• Patients must have advanced malignant solid tumours that are metastatic or unresectable
• At least one measurable or evaluable (non-measurable) lesion per RECIST 1.1 Part B only
• Patients must have:
• measurable disease per RECIST 1.1
• diagnosis of one of the following
• Advanced Non-Small Cell Lung Cancer -Squamous Histology (NSCLC-SQ) with no more than 2 lines of chemotherapy for advanced/metastatic disease ( prior EGFR directed treatment is permitted) or
• Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck (R/M SCCHN) no more than 2 lines of chemotherapy for advanced disease and no more than 1 line of prior cetuximab permitted.
• Other malignant solid tumours except sarcomas (for metastatic colorectal cancer, only wild type KRAS are permitted) Part A and B
• Age 18 years or older
• Written informed consent that is consistent with ICH-GCP guidelines and local law.
• Advanced disease for whom standard treatment is ineffective or no longer effective
• Recovered from previous therapy related AE to \</= Grade 1 at the study entry (except, for stable sensory neuropathy \</= Grade 2 and alopecia)
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
• Adequate organ function as defined by the following criteria:

You may not qualify if:

• Chemotherapy, biological therapy or investigational agents within 4 weeks prior to the start of study treatment.
• Hormonal anti-cancer treatment within 2 weeks prior to the start of study treatment (continued use of anti-androgens and/or gonadorelin analogues \[LHRH\] is permitted)
• Radiotherapy within 4 weeks prior to the start of study treatment, except as follows:
• Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to study treatment, and
• Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
• Major surgery (as judged by the investigator) within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
• Known hypersensitivity to afatinib or the excipients of any of the trial drugs
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior start treatment.
• Female patients of childbearing potential who:
• are nursing or
• are pregnant or
• are not using an acceptable method of birth control or do not plan to continue using this method throughout the study and/or do not agree to submit to pregnancy testing required by this protocol.
• Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
• Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured.
• Requiring treatment with any of the prohibited concomitant medications listed in the protocol that can not be stopped for the duration of trial participation

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (2)

1200.122.33001 Boehringer Ingelheim Investigational Site

Villejuif, France

Location

1200.122.34001 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

Related Publications (1)

• Gazzah A, Boni V, Soria JC, Calles A, Even C, Doger B, Mahjoubi L, Bahleda R, Ould-Kaci M, Esler A, Nazabadioko S, Calvo E. A phase 1b study of afatinib in combination with standard-dose cetuximab in patients with advanced solid tumours. Eur J Cancer. 2018 Nov;104:1-8. doi: 10.1016/j.ejca.2018.07.011. Epub 2018 Oct 1.

  PMID: 30278378 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2013
• First Posted: December 25, 2013
• Study Start: December 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: April 1, 2016
• Last Updated: June 22, 2017
• Results First Posted: February 12, 2016

Record last verified: 2017-05

Locations

ES (1); FR (1)