NCT02768337

Brief Summary

Proof of principle phase 1b / randomised phase 2 study of afatinib penetration into cerebral metastases for patients undergoing neurosurgical resection, both with and without prior low-dose, targeted radiotherapy.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at P25-P50 for phase_1 lung-cancer

Timeline
Completed

Started Mar 2015

Longer than P75 for phase_1 lung-cancer

Geographic Reach
1 country

6 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 10, 2015

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

April 28, 2016

Completed
13 days until next milestone

First Posted

Study publicly available on registry

May 11, 2016

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 12, 2020

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

August 12, 2021

Completed
Last Updated

January 31, 2024

Status Verified

January 1, 2024

Enrollment Period

5.4 years

First QC Date

April 28, 2016

Last Update Submit

January 30, 2024

Conditions

Lung CancerBreast CancerBrain CancerAdvanced Breast CancerAdvanced Lung Cancer

Keywords

brain metastasisoperable brain metastasis

Outcome Measures

Primary Outcomes (1)

  • Ratio of afatinib concentration in: [resected brain metastases] / [plasma] - each measured in (ng/mL) on day 12

    Day 12 of treatment

Secondary Outcomes (1)

  • Safety of afatinib alone and combined with targeted low-dose radiotherapy - assessed by number of participants with treatment- related adverse events as assessed by CTCAE v4.0

    From consent to Day 41+/-7 days

Study Arms (3)

Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D)

OTHER

No targeted radiotherapy. Afatinib at Recommended Phase 2 Dose for 11 days.

Drug: Afatinib

Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy

EXPERIMENTAL

Patient will receive the RP2D of afatinib for 11 days and will receive targeted radiotherapy at a dose level of 2 Gy on Day 10 of treatment.

Drug: AfatinibRadiation: 2 Gy targeted radiotherapy

Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy

EXPERIMENTAL

Patient will receive the RP2D of afatinib for 11 days and will receive targeted radiotherapy at a dose level of 4 Gy on Day 10 of treatment.

Drug: AfatinibRadiation: 4 Gy targeted radiotherapy

Interventions

AfatinibDRUG
Also known as: Giotrif
Arm 1: Afatinib only at Recommended Phase 2 dose (RP2D)Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapyArm 3: Afatinib RP2D + 4 Gy targeted radiotherapy
2 Gy targeted radiotherapyRADIATION
Arm 2: Afatinib RP2D + 2 Gy targeted radiotherapy
4 Gy targeted radiotherapyRADIATION
Arm 3: Afatinib RP2D + 4 Gy targeted radiotherapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Operable brain metastases from likely breast or lung origin as determined by local MDT. Both of the following groups of patients may be considered eligible:
  • Patients with a past history of histologically/cytologically confirmed breast or lung cancer, now presenting with a new likely brain metastasis from that primary.
  • Patients presenting with new, primary (breast/lung) tumours, plus synchronous, operable brain metastases, without pre-op tissue diagnosis.
  • ECOG performance score 0, 1 or 2.
  • Aged 18 years or older.
  • Written informed consent.
  • Patients are allowed to take oral corticosteroids however the plan should be for them to receive a stable dose of corticosteroids for at least 3 days before neurosurgery (i.e. trial days 10, 11, 12)

You may not qualify if:

  • History or presence of existing interstitial lung disease.
  • Current clinically significant impairment of cardiac function (greater than Class II according to New York Heart Association \[NYHA\] classification).
  • Unstable ischemic heart disease within the last 6 months, including myocardial infarction.
  • Presence of QTc interval prolongation \>480 ms.
  • Clinically significant corneal or conjunctival eye disease.
  • Clinically significant skin diseases such as psoriasis, rash or atopic dermatitis.
  • Clinically significant impairment of GI function or GI disease including total gastrectomy that may alter the absorption of afatinib.
  • Clinically significant, active peptic ulcer disease.
  • Known positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody or patients with any untreated serious infections.
  • Pregnancy and contraception:
  • Female patients of child bearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration/randomisation, and must use an effective method of contraception at least 1 week prior to treatment, during treatment and for at least 28 days after the final dose of study drug. Acceptable methods are:
  • True abstinence (this must be the patients usual and preferred lifestyle, not just for the duration of the study) Oral contraceptive (either combined or progestogen alone) Contraceptive implant, injections or patches Vaginal ring Intrauterine device (IUD, coil or intrauterine system) Condom and cap Diaphragm plus spermicide Tubal Ligation
  • A female patient of child bearing potential is defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if aged 55 years or younger or 12 months if aged 56 years or older.
  • Men must use one of the following, reliable forms to contraception for the entire duration of treatment and for 28 days after the final dose of study drug:
  • Condom plus spermicide even if female partner is using another method of contraception (Men should also use a condom to protect male partners, or female partners who are pregnant or breast feeding, from exposure to the study medicine in semen).
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Lung NeoplasmsBreast NeoplasmsBrain Neoplasms

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Respiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesCentral Nervous System NeoplasmsNervous System NeoplasmsBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

AmidesOrganic ChemicalsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Richard Baird, MD PhD

    Cambridge University Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Dr Richard Baird

Study Record Dates

First Submitted

April 28, 2016

First Posted

May 11, 2016

Study Start

March 10, 2015

Primary Completion

August 12, 2020

Study Completion

August 12, 2021

Last Updated

January 31, 2024

Record last verified: 2024-01

Locations

GB(6)