Phase I/II study with the combination of dacomitinib and PD-0325901 in metastatic non-small cell lung cancer with a mutation in the KRAS gene

Phase 1

• Conditions: non-small cell lung cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003299-10-NL
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-09-27
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 132

Inclusion Criteria

1. Histological or cytological proof of metastatic NSCLC
2. Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wildtype (exon 9 and 20).
3. Age >= 18 years.
4. Able and willing to give written informed consent.
5. WHO performance status of 0, 1.
6. Able and willing to undergo blood sampling for PK and PD analysis.
7. Able and willing to undergo tumor biopsies prior to start, while on study treatment and upon progression of disease
8. All toxicities related to prior treatment should have resolved to CTCAE grade 1 or less (excluding alopecia)
9. Life expectancy >= 3 months allowing adequate follow up of toxicity evaluation and antitumor activity.
10. Measurable disease according to RECIST 1.1 criteria
11. Adequate organ system function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion Criteria

1. Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment.
2. History of additional primary malignancies
3. Two or more prior lines of therapy for advanced disease (PART B only).
4. Symptomatic or untreated leptomeningeal disease.
5. Symptomatic brain metastasis.
6. Patients previously treated with any targeted drug combination known to interfere with EGFR, HER-2, HER-3, HER-4 or MAPK- and PI3K-pathway components, including inhibitors of PTEN, PI3K, AKT, mTOR, BRAF, MEK and ERK.
7. History of interstitial lung disease or pneumonitis
8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral dacomitinib/PD-0325901 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
9. Woman who are pregnant or breast feeding.
10. Unreliable contraceptive methods.
11. Radio-, immuno- or chemotherapy within the last 4 weeks prior to receiving the first dose of investigational treatment. Palliative radiation (1x 8Gy) is allowed.
12. Patients who have undergone any major surgery within the last 2 weeks prior to starting study drug or who would not have fully recovered from previous surgery.
13. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients.
14. Patients with a known history of hepatitis B or C.
15. Patients with retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), or with a history of uveitis, retinal vein occlusion, central serous retinopathy or retinal detachment.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified