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Phase I Trial of Cisplatin and Pemetrexed in Combination With Panobinostat in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer

Phase 1
18 Years
Open (Enrolling)
Solid Tumors, Non-Small Cell Lung Cancer (NSCLC)

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Trial Information

Phase I Trial of Cisplatin and Pemetrexed in Combination With Panobinostat in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer

The purpose of this phase I study of oral panobinostat plus cisplatin and pemetrexed is to
determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) in patients
with advanced solid tumors, with an emphasis in non-small cell lung cancer. Another purpose
of this study is to find out if oral panobinostat in combination with cisplatin and
pemetrexed can be administered safely without significant increase in toxicity and that the
combination will increase efficacy compared to platinum-based doublet chemotherapy alone.

Inclusion Criteria:

- Histological or cytological proven advanced solid tumors for which curative standard
treatments are not available.

- Must have measurable or evaluable disease.

- Male or female patients aged ≥ 18 years old.

- Any number of prior chemotherapy regimens.

- ECOG Performance Status of ≤ 2 with a life expectancy greater than 3 months.

- Clinically euthyroid (may be on thyroid hormone replacement)

- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
within 7 days of the first administration of study treatment.

- Ability to provide written informed consent

- Must meet the following laboratory criteria:


- Neutrophil count of ≥ 1.5 x 109/L

- Platelet count of ≥ 100 x 109/L

- Hemoglobin ≥ 9 g/dL


- AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the
transaminase elevation is due to disease involvement

- Serum bilirubin ≤ 1.5 x ULN

- Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min

- Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN and ≤ ULN

- Serum potassium ≥ LLN and ≤ ULN

- Serum sodium ≥ LLN and ≤ ULN

- Serum albumin ≥ LLN or 3g/dl

- Serum magnesium ≥ LLN and ≤ ULN

- Any elevated Alkaline Phosphatase due to bone metastasis can be enrolled

Exclusion Criteria:

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

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

- 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.

- Impaired cardiac function

- Other concurrent severe and/or uncontrolled medical conditions that could cause
unacceptable safety risks or compromise compliance with the protocol

- Concomitant use of drugs which are generally recognized to have a risk of causing
torsades de pointes where such treatment cannot be discontinued or switched to a
different medication prior to starting study drug

- Patients with unresolved diarrhea ≥ CTCAE grade 2

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral panobinostat. Inability to swallow panobinostat capsules

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

- Uncontrolled or symptomatic brain metastases.

- 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

- 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.

- Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline
testing for HIV and hepatitis C is not required

- Any significant history of non-compliance to medical regimens or with inability to
grant a reliable informed consent

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and feasibility of oral panobinostat in combination with cisplatin and pemetrexed

Outcome Description:

Safety assessments will consist of monitoring and recording all adverse events and serious adverse events, the regular monitoring of hematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examination. Safety and tolerability will be assessed according to the NCI CTCAE v4.

Outcome Time Frame:

Within ±3 days of the scheduled day of assessment except for adverse events that will be evaluated continuously through the study. The expected time frame for this outcome measure is 18 weeks (or six cycles)

Safety Issue:


Principal Investigator

David Gandara, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Davis


United States: Food and Drug Administration

Study ID:




Start Date:

April 2011

Completion Date:

December 2014

Related Keywords:

  • Solid Tumors
  • Non-Small Cell Lung Cancer (NSCLC)
  • panobinostat
  • cisplatin
  • pemetrexed
  • dose escalation
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasms



University of California Davis Cancer Center Sacramento, California  95817