The Safety and Efficacy Study of Afatinib (CT) Compared With Afatinib (GIOTRIF) in Patients With Solid Tumors (Including Mutations Identified EGFR)

• Register: ClinicalTrials.gov
• Last refreshed on: 3 August 2015
• Main ID: NCT02430727
• Date of registration: 27/04/2015
• Prospective Registration: No
• Primary sponsor: Cancer Centre of Monoclonal Therapy, LLC
• Public title: The Safety and Efficacy Study of Afatinib (CT) Compared With Afatinib (GIOTRIF) in Patients With Solid Tumors (Including Mutations Identified EGFR)
• Scientific title: The Safety and Efficacy Study of Afatinib (CT) Compared With Afatinib (GIOTRIF) in Patients With Solid Tumors (Including Mutations Identified EGFR)
• Date of first enrolment: July 2012
• Target sample size: 148
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02430727
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Belarus, Russian Federation, Ukraine

Contacts

• Name: Viktor Lanevskij, PhD
• Affiliation: Cancer Center

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

- Histologically-confirmed WHO Grade IV newly diagnosed malignant glioma.

- Proven MGMT gene promoter methylation status

- Available early postoperative Gd-enhanced MRI (within 72 hours after initial
surgery). In case a patient did not perform a Gd-enhanced MRI within 72 hours post
surgery, a Gd-MRI is to be performed prior to start of study treatment.

- 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.

Histological/Cytological confirmed diagnosis of malignant solid tumours (exclusion of
sarcomas)

- Advanced disease for whom standard treatment is ineffective or no longer effective

- Recovered from previous therapy related AE to for stable sensory neuropathy
- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.

- Adequate organ function as defined by the following criteria:

- LVEF >50% or within institutional values

- Absolute neutrophil count (ANC) >1500/ mm3

- Platelet count >75.000/ mm3

- Estimated creatinine clearance > 45ml/ min

- Total bilirubin<1.5 times upper limit of institutional normal

- Aspartate amino transferase (AST) or alanine amino transferase (ALT) <3 x upper limit
of institutional normal (ULN) (if related to liver metastases< 5xULN)

Exclusion Criteria:

- 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

- Known pre-existing interstitial lung disease

- Any history or presence of poorly controlled gastrointestinal disorders that could
affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis,
chronic diarrhea, malabsorption)

- Active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA),
active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV
carrier.

- Prior participation in an afatinib clinical study, even if not assigned to afatinib
treatment.

- Meningeal carcinomatosis

- Patients with brain or subdural metastases are not eligible, unless they have
completed - local therapy and have discontinued the use of corticosteroids or have
been on stable dose of corticosteroids for at least 4 weeks before starting study
treatment. Any symptoms attributed to brain metastases must be stable for at least 4
weeks before starting study treatment.

- Any SPC listed contra-indications for cetuximab

- Use of alcohol or drugs incompatible with patient participation in the study in the
investigator's opinion.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Glioblastoma

Solid Tumors

Intervention(s)

Drug: GIOTRIF

Drug: Afatinib (CT)

Primary Outcome(s)

The effectiveness of Afatinib (CT), in comparison with GIOTRIF (Afatinib) confirmed objective response (ORR) on 12-24-52 - weeks treatment of patients with advanced solid tumors [Time Frame: up to 54 weeks]

Secondary Outcome(s)

Number of Participants With Progression Free Survival (PFS) [Time Frame: up to 54 weeks]

Secondary ID(s)

XTPTC-309-96

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Boehringer Ingelheim

NCRI Clinical Studies Groups