A Study of HSP90 Inhibitor AT13387 Alone and in Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

Study ID
STU 082012-091

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • UT Southwestern Ambulatory Services
  • UT Southwestern University Hospital—St. Paul
  • UT Southwestern University Hospital– Zale Lipshy

Contact
Laurin Priddy
214-648-1688
laurin.loudat@utsouthwestern.edu

Principal Investigator
Joan Schiller

Summary

This is a 3-part Phase 1-2 study in subjects with anaplastic lymphoma kinase (aLK) + or other potentially crizotinib-sensitive nSCLC who have been receiving crizotinib. Part a will be conducted initially. once Part a is successfully completed, Parts B and C will be conducted in parallel.

Part B is an open-label, randomized design comparing crizotinib alone to the combination of
crizotinib with aT13387 to better assess the benefit that is gained by the addition of aT13387 to
crizotinib as subjects may have an improved PFS or other efficacy measures with the addition of aT13387. Crossover is allowed to permit crizotinib alone
patients to receive the experimental treatment aT13387 with crizotinib following progression to
give patients another chance of improvement in efficacy measures.

in Part C, only subjects progressing after crizotinib treatment are included. Since those subjects
are not expected to respond to crizotinib monotherapy, an open-label, randomized, Simon's 2-
stage design will be used to assess the achievement of objective response, either with aT13387
alone or by adding aT13387 to crizotinib. The minimum oRR of interest in progressing patients
is [Greater Than]10% in a Simon's 2-stage design, with the desired response rate of 30%.

Participant Eligibility

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 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. b. 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 (ECOG) Performance Status <=2 for
Parts B and C;
6. Have adequate bone marrow function defined as absolute neutrophil count >1.5 K/[MICRO-SYMBOL]L and
platelet count >75 K/[MICRO-SYMBOL]L;
7. Have adequate hepatic function, defined as bilirubin <=1.5 x ULN and alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) <=2.5 x ULN (ALT and AST <=5 x ULN, if liver
metastases are present);
8. Have adequate renal function, defined as serum creatinine <=1.25 x ULN or estimated creatinine
clearance >=50mL/min;
9. Have adequate cardiac function and normal cardiac repolarization defined as:
a. QTc <480 msec and
b. LVEF >=50% or within institutional limits of normal by echocardiogram (ECHO) or
multigated acquisition (MUGA) 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 follicle-stimulating 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
12. Able and willing to provide written informed consent and to comply with the protocol and study
procedures.