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Phase I/ II Trial of Carboplatin and Etoposide Plus LBH589 for Previously Untreated Extensive Stage Small Cell Lung Cancer

Phase 1/Phase 2
18 Years
Not Enrolling
Small Cell Lung Cancer

Thank you

Trial Information

Phase I/ II Trial of Carboplatin and Etoposide Plus LBH589 for Previously Untreated Extensive Stage Small Cell Lung Cancer

Treatment plan

- LBH589 will be given in oral formulation starting at a dose of 10 mg (Dose Level 1)
three times per week (doses will be given at least 2 days apart, e.g. Monday,
Wednesday, Friday), 2 out of 3 weeks dosing schedule.

- After establishing the MTD of LBH589 at a 2 out 3 weeks dosing schedule, a 3 out of 3
weeks dosing schedule will be tested at that dose, and this schedule will be adopted in
the absence of limiting toxicities.

- Carboplatin will be given on day 1, every 21 days, and etoposide on days 1,2,3 every 21
days for up to 6 cycles. LBH589 will be continued weekly, three times-a-week, without
interruption after completion of 6 cycles of combination chemotherapy until
progression, or intolerable toxicities.

In the phase I part and for cycle 1 only, for the purpose of the PK studies LBH589 will
start the week prior to the first carboplatin/etoposide cycle and PD studies will be
performed (week -1).

Study design and sample size:

This is a phase I/II study. Phase I: 15-24 patients (estimated; Three to six patients will
be enrolled at each dose level); Phase II: 39 patients.

Inclusion Criteria

Inclusion criteria Note: subjects with screening labs outside of the normal institutional
limits (WNL) definition may be allowed if determined by the treating physician and the PI
that the deviation from the normal institutional limits is minor.

1. Patients with extensive stage SCLC who have not received prior chemotherapy

For the phase I portion of the study only (and not for phase II), patients with
progressive advanced or metastatic cancer (any histology) are allowed. These patients
must have progressed on one or more standard therapies for the disease, or have
disease which is known to be incurable and poorly responsive to available systemic
therapies. Priority will be given in patients with neuroendocrine tumors, such as:

1. Carcinoid

2. Extrapulmonary small cell carcinoma

3. Peripheral neuroepithelioma

4. Merkel cell tumor

5. Neuroblastoma

6. Large cell neuroendocrine cancer

7. Esthesioneuroblastoma and other neuroendocrine carcinomas of the head and neck
1.2 For the phase I portion of the study only (and not for phase II), patients
are allowed to have prior chemotherapy except for Etoposide and LBH589.

2. Measurable disease (RECIST) (for phase II part only)

3. Patients may not have received prior HDACi therapy, including valproic acid, for the
treatment of any medical condition.

4. ECOG Performance Status of ≤ 2 (see Appendix 4)

5. Aged ≥ 18 years old and ability to provide written informed consent obtained prior to
participation in the study and any related procedures being performed

6. Patients must meet the following laboratory criteria:

- Hematology:

- Absolute neutrophil count (ANC) ≥ 1500/mm³

- Platelets ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Biochemistry:

- Total Bilirubin within normal institutional limits.

- AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN)

- Renal: serum creatinine < 2 ULN

- Total serum calcium (corrected for serum albumin) or ionized calcium WNL

- If total serum calcium is elevated >ULN, confirm with ionized Calcium.

- Serum potassium WNl WNL

- Serum sodium WNL

- Serum albumin WNL

- Patients with any elevated Alkaline Phosphatase due to bone metastasis can
be enrolled

7. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional
normal as interpreted by the reading cardiologist.

8. TSH and free T4 within normal limits (patients may be on thyroid hormone replacement)

9. Blood pressure of <140/90.

10. Patients must have fully recovered from the effects of any prior surgery or radiation
therapy. A minimum time period of 3 weeks should elapse between the completion of
extensive radiation therapy for recurrent/metastatic disease and enrollment in the

11. If patient has history of brain metastases, brain lesions should have been treated
with surgery and/or radiation and be stable on repeat imaging.

12. No history of prior malignancy, with the exception of curatively treated squamous
cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a
3-year disease-free interval.

13. Patients should temporarily stop certain Nonsteroidal Anti-inflammatory Drug (NSAIDS)
starting 5 days prior to protocol therapy, as described in 6.5.1.

14. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days of the first administration of study treatment and must be willing to
use two methods of contraception one of them being a barrier method during the study
and for 3 months after last study drug administration. Sexually active males and
their female partners must agree to use an accepted and effective method of
contraception (hormonal or barrier methods, abstinence) prior to study entry and for
the duration of the study. Oral contraceptives are generally metabolized by CYP3A4.
Since the potential of LBH589 to induce CYP3A4 is unknown, patients who are using
oral contraceptives as a method of contraception, and are sexually active, should use
another effective contraceptive method.

15. All patients must have given signed, informed consent prior to registration on study.

Exclusion criteria

1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

2. Patients who will need valproic acid for any medical condition during the study or
within 5 days prior to first LBH589 treatment

3. Impaired cardiac function including any one of the following:

- Screening ECG with a QTc > 450 msec confirmed by treating physician investigator
prior to enrollment to the study

- Patients with congenital long QT syndrome

- History of sustained ventricular tachycardia

- Any history of ventricular fibrillation or torsades de pointes

- Bradycardia defined as heart rate < 50 beats per minute. Patients with a
pacemaker and heart rate ≥ 50 beats per minute are eligible.

- Patients with a myocardial infarction or unstable angina within 6 months of
study entry

- Congestive heart failure (NY Heart Association class III or IV)

- Right bundle branch block and left anterior hemiblock (bifascicular block)

4. Uncontrolled hypertension. Patients with history of hypertension must be
well-controlled (≤140/90) on a stable regimen of anti-hypertensive therapy.

5. Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix

6. Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)

7. Patients with unresolved diarrhea > CTCAE grade 1

8. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral LBH589

9. Other concurrent severe and/or uncontrolled medical conditions

10. Patients who have received chemotherapy, any investigational drug or undergone major
surgery < 4 weeks prior to starting study drug or who have not recovered from side
effects of such therapy.

11. Concomitant use of any anti-cancer therapy or radiation therapy.

12. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP)
not willing to use a double barrier method of contraception during the study and 3
months after the end of treatment. One of these methods of contraception must be a
barrier method. WOCBP are defined as sexually mature women who have not undergone a
hysterectomy or who have not been naturally postmenopausal for at least 12
consecutive months (i.e., who has had menses any time in the preceding 12 consecutive
months). Women of childbearing potential (WOCBP) must have a negative serum
pregnancy test within 7 days of the first administration of oral LBH589.

13. Male patients whose sexual partners are WOCBP not using a double method of
contraception during the study and 3 months after the end of treatment. One of these
methods must be a condom

14. Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis
C; baseline testing for HIV and hepatitis C is not required

15. Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent.

16. Patients with peripheral neuropathy ≥ CTCAE grade 2.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluation of Target Lesions

Outcome Time Frame:

18 weeks

Safety Issue:


Principal Investigator

Ahmad A Tarhini, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

June 2011

Related Keywords:

  • Small Cell Lung Cancer
  • Lung Neoplasms
  • Small Cell Lung Carcinoma



University of Pittsburgh Pittsburgh, Pennsylvania  15261