Phase I/II study with the combination of afatinib and selumetinib in advanced KRAS mutant positive and PIK3CA wildtype non-small cell lung cancer and colorectal cancer

Completed

• Conditions: colorectal cancer; non-small cell lung cancer; 10027476

• Registration Number: NL-OMON47757
• Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Trial is onging in other countries

Detailed Description

Not available

Study Timeline

• Study Completion: 2020-05-14
• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 28

Inclusion Criteria

1. Histological or cytological proof of advanced NSCLC or CRC;
2. Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation
and PIK3CA wildtype (defined as absence of mutations in exon 9 and 20).
3. Age ><=18 years.
4. Able and willing to give written informed consent.
5. WHO performance status of 0 or 1.
6. Able and willing to undergo blood sampling for PK and PD analysis.
7. Able and willing to undergo a tumor biopsy prior to start, after two weeks
on therapy (Part A) and upon progression of disease
8. Life expectancy ><=3 months allowing adequate follow up of toxicity
evaluation and antitumor activity.
9. Measurable disease according to RECIST 1.1

Exclusion Criteria

1. Any treatment with investigational drugs within 30 days prior to receiving
the first dose of investigational treatment.
2.History of another malignancy
Exception PART A: Patients who have been disease-free for at least 3 years, or
patients with a history of completely resected non-melanoma skin cancer and/or
patients with indolent second malignancies are eligible.
Exception PART B: Adequately treated carcinoma in situ of the cervix and
adequately treated basal cell carcinoma of the skin.
3. Symptomatic or untreated leptomeningeal disease.
4. Symptomatic brain metastasis. Patients previously treated or untreated for
these conditions that are asymptomatic in the absence of corticosteroid and
anticonvulsant therapy (for at least 4 weeks) are allowed to enrol.
Radiotherapy for brain metastasis must have been completed at least 6 weeks
prior to start of study treatment. Brain metastasis must be stable with
verification by imaging (e.g. brain MRI or CT completed at screening
demonstrating no current evidence of progressive brain metastases).
5. Patients previously treated with any drug combination known to interfere
with EGFR, HER2, HER3, HER4 or MAPK- and PI3K-pathway components, including
inhibitors of PTEN, PI3K, AKT, mTOR, BRAF, MEK and ERK.
6. History of interstitial lung disease or pneumonitis
7. Radio-, immuno- or chemotherapy within the last 2 weeks prior to receiving
the first dose of investigational treatment. Palliative radiation (1x 8Gy) is
allowed.
8. (History of) Opthalmological diseases
9. Patients with left ventricular ejection fraction (LVEF) < 55%.
10. Patients with cardiac comorbidities

Study & Design

• Study Type: Interventional
• Study Design: Not specified