A study to test a new product AT13387 in lung cancer.
- Conditions
- on-small cell lung cancer (NSCLC) which represents 85% of all lung cancers.MedDRA version: 17.0Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001575-37-ES
- Lead Sponsor
- Astex Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 220
Subjects who meet all of the following criteria will be eligible to participate in the study:
1. Men or women ? 18 years of age;
2. Have a histologically or cytologically confirmed NSCLC that is ALK+ or has other mutations or rearrangements that are potentially sensitive to crizotinib and have been receiving or have received crizotinib, regardless of other prior anticancer therapies including other ALK inhibitors;
3. Presence of disease as described in Inclusion Criterion 4 for the different parts of the study;
4.a. In Part A, subjects must have received and been tolerant to at least 8 weeks of crizotinib 250 mg BID in the past regardless of when it was taken and the number of other intervening anticancer therapies, including other ALK inhibitors that may have been taken since the last dose of crizotinib. In part A, subjects with any response category may be enrolled as long as there is a chance of potential added benefit from continuing crizotinib in combination with AT13387 even if there is evidence of disease progression while on crizotinib monotherapy;
b. In Part B, subjects who are currently receiving and tolerating crizotinib and have not progressed by RECIST 1.1. or have not yet started but are eligible to receive crizotinib; and
c. In Part C, only subjects who are progressing or had previously progressed based on RECIST 1.1 at any time on crizotinib (including those who went on to receive other therapy including other ALK inhibitors before enrollment) will be enrolled;
5. Eastern Cooperative Oncology Group Performance Status ?1 for Part A and ?2 for Parts B and C;
6. Have adequate bone marrow function defined as absolute neutrophil count >1.5 K/?L and platelet count >75 K/?L;
7. Have adequate hepatic function, defined as bilirubin ?1.5 × upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ?2.5 × ULN (ALT and AST ?5 × ULN, if liver metastases are present);
8. Have adequate renal function, defined as serum creatinine ?1.25 × ULN or estimated creatinine clearance >50 mL/min;
9. Have adequate cardiac function and normal cardiac repolarization defined as:
a. QTc ?480 msec and
b. Left ventricular ejection fraction ? 50% or within institutional limits of normal by echocardiogram or multigated acquisition scan;
10. Female subjects who are either:
a. Not pregnant (must have a negative pregnancy test at screening) or breastfeeding and not planning to become pregnant during the study;
b. Not of childbearing potential, defined as one who has been postmenopausal (no menses AND either age ?65 years or folliclestimulating hormone levels in the menopausal range) for at least 1 year, has been surgically sterilized by bilateral oophorectomy, or has had a hysterectomy;
11. Subjects and their female partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months following the last dose of the study drug. Effective contraception includes methods such as oral contraceptives, double-barrier method
(condom plus spermicide or diaphragm), or abstaining from sexual intercourse; and
12. Able and willing to provide written informed consent and to comply with the protocol and study procedures.
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 228
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 160
Subjects who meet any of the following criteria will be excluded from the study:
1. Prior anti-cancer treatment with any heat shock protein 90 (HSP90) inhibitor;
2. Have received chemotherapy, radiation therapy, or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug unless the washout period of those treatments has clearly exceeded 5 pharmacokinetic half-lives and any associated clinically significant toxicity has resolved to ?Grade 1;
3. Subjects with a prior malignancy other than adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, lowgrade cervical cancer, non-metastatic prostate cancer with normal PSA, or other cancer from which the subject has been disease-free for at least 3 years;
4. Known symptomatic brain or central nervous system metastases (Note: Patients with asymptomatic brain metastases or any brain metastases that have been stable for ? 4 weeks may be included);
5. Documented QTc prolongation >480 msec related to crizotinib on multiple measurements in electrocardiograms (ECGs) during prior
treatment with crizotinib;
6. ? Grade 2 bilirubin or transaminases on multiple measurements related to crizotinib while receiving crizotinib;
7. ? Grade 2 visual disturbances related to crizotinib while receiving crizotinib treatment;
8. Congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or clinically significant uncorrected electrolyte imbalance, particularly hypokalemia <3 mmol/L unless corrected;
9. Presence of a serious illness, active infection, medical condition, organ system dysfunction, or other factors which, in the Investigator's opinion, could compromise the subject's safety, negatively interact with AT13387, or compromise the integrity of the study outcomes;
10. Hypersensitivity to AT13387 or other components of the drug product;
11. For Part C, subjects who discontinued treatment with crizotinib due to a crizotinib-related toxicity;
12. Treatment with any investigational drug within 3 weeks prior to the first dose of study drug or at least until any residual clinically significant toxicity from the investigational agent has resolved to ? Grade 1 and at least 5 pharmacokinetic half-lives (if known) have elapsed;
13. Subjects who are a poor medical risk because of other systemic diseases or active uncontrolled infections; or
14. Known history of human immunodeficiency virus or seropositive test for hepatitis C virus or hepatitis B virus.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method