Study to Assess Osimertinib in Patients w/ Adv Solid Tumours & Normal Kidney Function or Severe Kidney Impairment

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to assess the effect of severe renal impairment on the levels of AZD9291 in the blood in patients with advanced solid tumours compared to patients with normal renal function

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Quintiles, Inc.
• Treatments: Osimertinib

Criteria

Inclusion criteria:

1. For inclusion as a patient with severe renal impairment patient must have stable severe renal impairment (CrCl <30 mL/min at screening), for at least 2 months prior to the study.

2. For inclusion as a patient with normal renal function, patient must have CrCl ≥90 mL/min at screening.

3. >18 years old

4. Histological or cytological confirmation of a solid, malignant tumour (excluding lymphoma) that is refractory to standard therapies or for which no standard therapies exist. Tumours in which inhibition of the EGFR pathway is considered relevant by the Investigator are not mandated but are encouraged.

5. ECOG performance status ≤2

6. Life expectancy of ≥12 weeks

7. BMI 18-35.

8. Females should be using adequate contraceptive measures and must have a negative pregnancy test prior to dosing if of child-bearing potential or must have evidence of non-child bearing potential

9. Males should use barrier contraception until 6 months after the last study drug is taken.

Exclusion criteria

1. Participation in another clinical study with an IP during the last 14 days (or a longer period, depending on the agents used).

2. Treatment with any of the following:

• Treatment with a 1st or 2nd generation EGFR-TKI within 8 days or approximately 5 half-lives, prior to the first dose of study drug.

• Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 14 days of the first dose of study drug.

• Osimertinib in the present study or has previously received a 3rd generation EGFR-TKI (eg, CO 1686).

• Major surgery within 4 weeks of the first dose of study drug.

• Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment

• Currently receiving medications or herbal supplements known to be potent inducers of CYP3A4. Patients in Part B and continued access must avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known potent inducer effects on CYP3A4.

3. Patients with severe renal impairment only: use of concurrent medication known to affect CrCl within 7 days of the first dose

4. Unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment; with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy

5. Spinal cord compression or brain metastases, unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment

6. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

• Absolute neutrophil count <1.5 x 109/L

• Platelet count <100 x 109/L

• Haemoglobin <90 g/L

• ALT >2.5 times the ULN if no demonstrable liver metastases or >5xULN in the presence of liver metastases

• AST >2.5xULN if no demonstrable liver metastases or > 5xULN in the presence of liver metastases

• Total bilirubin >1.5 times ULN if no liver metastases or >3xULN in the presence of liver metastases

7. Any of the following cardiac criteria:

• Mean resting QT interval QTcF >470 msec, obtained from 3 ECGs.

• Abnormalities in rhythm, conduction or morphology of resting ECG

• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval

8. Unable to swallow oral medication or patients with GI disorders or significant GI resection.

9. Medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.

10. Severe portal hypertension or surgical porto-systemic shunts.

11. Kidney transplant

12. On dialysis