A Phase I/II Multi-centre Study of AZD8931 in Combination with WeeklyPaclitaxel to Assess the Safety, Tolerability, Pharmacokinetics and Efficacyin Patients with Advanced Solid Tumours and in a Selected Population withLow HER2-expressing Locally Recurrent and/or Metastatic Breast Cancer(THYME) - THYME

Conditions: MedDRA version: 9.1Level: LLTClassification code 10049280Term: Solid tumour
Phase I part of the study: Advanced solid tumoursPhase II part of the study: Low HER2 expressing locally recurrent and/or metastatic breast cancer

Registration Number: EUCTR2009-010551-26-HU

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 192

Inclusion Criteria

All patients
1. Provision of signed, written informed consent
2. Age 18 years and older
3. Radiation therapy must be terminated at least 2 weeks prior to enrolment. Patients
must have recovered from the toxic effects of prior therapy
4. Suitable for paclitaxel therapy
5. Life expectancy of more than 12 weeks
6. Not previously randomised to treatment in this study
7. Females of non-childbearing status defined as one of the following criteria at
screening:- negative pregnancy test in women of childbearing potential- or women
who are permanently or surgically sterilised (hysterectomy and/or bilateral
oopherectomy and/or bilateral salpingectomy) - or postmenopausal (over 50 years
old and amenorrheic for 12 months following cessation of all exogenous hormonal
treatments, or over 57 years old)
8. Not pregnant or breastfeeding if female and of child-bearing potential
9. Female patients of child-bearing potential willing to use an acceptable highly
effective method of contraception during the study and for 3 months after the last
dose of IP. It is recommended that women should have been stable on their chosen
method of contraception for at least 3 months before entering the study.
Recommended methods of contraception are listed in Appendix J
10. No receipt of investigational drug within the 14 days or 5 half-lives, whichever is
longer, of the first dose of randomised therapy (AZD8931 or matching placebo) or
participated in a previous clinical study during the last 30 days prior to study entry

Phase I only
40. Male or female with histologically or cytologically confirmed solid, malignant
tumour which is refractory to standard therapies, or for which no standard therapies
exist. Inclusion is irrespective of stage of disease or extent of prior therapy
41. World Health Organisation (WHO) performance status 0 to 2
42. No evidence of ‘dry eye’: persistent symptoms of ocular surface irritation,
Schirmer’s test without anaesthesia of less than 5 mm in 5 minutes and tear breakup
time [TBUT] test of less than 10 seconds (if one of these is satisfactory, the
patient may be included – both of these parameters should be normal if the patient
is receiving anti-cholinergic medication. Eye conditions that are stable and of long
standing, such as scars from trauma, pinguecula, atrophic pterygia etc, should not be
considered as reasons to exclude the patient
43. Not wearing contact lens (patients should discontinue wearing contact lens from at
least 1 week prior to entering the study to 1 week following discontinuation of
AZD8931)
44. No recent acute changes in patient’s vision, or ongoing symptoms of ocular pain,
discomfort or irritation
45. No history of collagen vascular, chronic inflammatory or degenerative disease with eye involvement (eg, rheumatoid, Sjögren syndrome, systemic lupus erythematosus [SLE]) or of ocular surface disease (including Steven-Johnson syndrome, ocular cicatricial pemphigoid or chemical burns, herpes simplex or herpes zoster virus eye disease
46. No history of corneal surgery, including laser refractive surgery, within the past 3
years
47. Random blood glucose at screening =11.1 mmol/L, or random blood glucose
between 7 and 11 mmol/L AND fasting blood glucose =7 mmol/L
48. No uncontrolled diabetes mellitus (glycosylated haemoglobin [HbA1c] =9%)

Phase II only
49. Female patients with histologic or cytologic diagnosis of breast cancer with
evidence of unresectable and/or locally recurrent and/ or metastatic disease.
Lesions should n

Exclusion Criteria

All the points included in this section are restrictions
All patients
1. Female patients of child bearing potential must use an acceptable highly effective
method of contraception during the study, and for 3 months after the last dose of IP.
Recommended methods of contraception are listed in Appendix J
2. Patients should use sunglasses and sun cream with UVA and UVB protection
SPF>15 if exposed to sunlight and avoid use of sun tanning booths during the study
and for 3 months after the last dose of IP
3. Patients who are blood donors should not donate blood during the trial and for 3
months following their last dose of IP
4. All patients must avoid concomitant use of medications, herbal supplements and/or
ingestion of foods that significantly modulate CYP3A4 and/or CYP2D6 activity or
which are significantly metabolised by CYP3A4 and/or CYP2D6. Such drugs must
have been discontinued for an appropriate period before they enter screening and
for a period of 2 weeks after the last dose of AZD8931. Guidance on medications
to avoid and on washout periods is given in Appendix D
5. Refer to the Summary of Product Characteristics (SPC) for restrictions specific to
paclitaxel

Phase I only
6. No food is allowed from 2 hours before to 2 hours after taking IP
7. Male patients will be required to use reliable methods of contraception (condom)
during any sexual contact with a female of childbearing potential for the duration of
the study and until 12 weeks after the last dose of AZD8931 (even if he has
undergone successful vasectomy)
8. Male patients will be advised to abstain from sperm donation from first dose until
12 weeks following receipt of the last dose of AZD8931
9. Refrain from driving for 4 hours following ophthalmic examination if pupillary
dilatation performed
10. Patients should refrain from wearing contact lenses from at least 1week prior to
starting AZD8931 to 1 week after discontinuation of AZD8931

Phase II only
11. Patients should refrain from wearing contact lenses in excess of the recommended
daily duration during participation in the study
12. Patients should not receive any endocrine treatment whilst receiving IP