Clinical Trial VICCTHO1478
A Multi-arm, Phase Ib, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination with Ascending Doses of Novel Therapeutics in Patients with EGFRm+ Advanced NSCLC who have progressed following therapy with an EGFR TKI (TATTON)
- Protocol No. VICCTHO1478
- Open Date: 11/14/2014
- Staging: Phase I
- Age Group: Adults
- Scope: National
- Objective: To investigate the safety and tolerability of AZD9291 when given orally to patients with EGFRm+ NSCLC in combination with MEDI4736, AZD6094 or selumetinib who have progressed following prior therapy with an EGFR TKI agent, and define the combination dose(s) for further clinical evaluation.
- Disease Sites: Lung; Non Small Cell
- Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
- Drugs: AZD6094; AZD9291; MEDI4736; Selumetinib
- Participating Institutions: Vanderbilt University
- National Clinical Trial ID: NCT02143466
- Secondary Protocol No: D5160C00006
Patients are asked to take part in this research study because they have been diagnosed as having non-small cell lung cancer (NSCLC) that has returned after standard treatment. Patients will be given AZD9291 (which is a new anti-cancer treatment being developed by AstraZeneca) together with one of either MEDI4736, AZD6094 OR selumetinib (three other experimental treatments for advanced lung cancer). None of the study drugs in this study have yet been approved for use, and this study is part of a research project for collecting safety and efficacy (how well the drug works) data for the first time. These combinations of drugs have never been given to patients with advanced lung cancer before. The main purpose of the study is to work out a suitable combination dose appropriate for further clinical studies by looking at information on any potential side effects these combinations may cause and collecting data about how cancer responds to the combinations of drugs. This study will also look at the blood levels of the drugs and the action of the combination of the drugs in the body over a period of time and will show whether the drugs have an effect on the type of cancer being studied.
|Ages Eligible for Study:||18 Years and older|
|Genders Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
(summarized due to limitation of characters)
1. Written informed consent
2. Aged at least 18 years (20 years for Japan)
3. Histological or cytological confirmation diagnosis of EGFRm+ NSCLC. Confirmation from a previous archival sample that the tumour harbours an EGFRm+ known to be associated with EGFR TKI sensitivity.
4. Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI (on the last treatment administered prior to enrolling in the study)
Part B cMET+ve patients:
• No prior treatment with a 3rd generation TKI: at least one prior line of therapy with 1st or 2nd generation EGFR TKI, but not a 3rd generation (T790M-directed) EGFR TKI.
• Prior treatment with a 3rd generation TKI: at least one prior line of therapy with a 3rd generation (T790M-directed) EGFR TKI for EGFRm or T790M+ NSCLC.
Part B cMET-ve patients:
• T790M directed EGFR TKI patients only: their immediate prior therapy before entry into this study must be a T790M directed EGFR TKI.
• ≥2nd line cohort: patients must have progressed while on treatment with an EGFR TKI (T790M directed EGFR TKIs are permitted). Other prior lines of therapy may have been given.
Part D cMET-ve patients:
No prior treatment with a 3rd generation TKI, T790M negative:
Patients must have received at least one prior line of therapy with 1st or 2nd generation EGFR TKI, but not a 3rd generation (T790M directed) EGFR TKI.
5. cMET status: Prior to study entry, local confirmation of tumour cMET status is acceptable, a central result will be confirmed retrospectively. If a local test is not available, central confirmation of tumour cMET status must be obtained prior to study entry.
T790M status: Local confirmation of tumour T790M status is acceptable, a central result will be confirmed retrospectively. If local testing is performed with the Cobas® EGFR Mutation Test, the central confirmation is not required.
6. At least one lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with CT or MRI which is suitable for accurate repeated measurements
7. WHO performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
8. Females should be using adequate contraceptive measures, must not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential.
Exclusion Criteria (summary):
• Treatment with an EGFR TKI within approximately 5x half-life of the first dose of study treatment. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment. Patients currently receiving (or unable to stop use) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior). For AZD6094 patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose, medications known to be strong inhibitors of CYP1A2. Prior AZD9291 dosing in the present study. Prior or current treatment with AZD6094 or another cMET inhibitor (if allocated to AZD9291 + AZD6094). Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within ≥4 weeks of the first dose of study treatment. Major (or anticipated major) surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study treatment. Currently receiving treatment with warfarin sodium.
• With the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy, any unresolved toxicities from prior therapy and/or pre-study biopsies greater than CTCAE Grade 1 at the time of starting study treatment.
• Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 2 weeks prior to start of study treatment.
• Severe or uncontrolled systemic diseases; known serious active infection; active hepatitis B or C; cardiac disease; inadequate bone marrow reserve or organ function or coagulation parameters; inadequate liver or renal function; GI events that would preclude adequate absorption, distribution, metabolism or excretion of AZD9291, AZD6094 or selumetinib; hipersensitivity to IP or similar drugs
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.