Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Study of Cisplatin and Pemetrexed in Combination With Panobinostat in Solid Tumors

This study is ongoing, but not recruiting participants.
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University of California, Davis Identifier:
First received: April 11, 2011
Last updated: December 12, 2014
Last verified: December 2014

The purpose of this study is to find out if panobinostat taken with cisplatin and pemetrexed can be used safely without increasing side effects and that the combination will have a better effect than platinum-based doublet chemotherapy alone.

Condition Intervention Phase
Solid Tumors
Non-Small Cell Lung Cancer (NSCLC)
Drug: Panobinostat, Cisplatin, Pemetrexed
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Cisplatin and Pemetrexed in Combination With Panobinostat in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer

Resource links provided by NLM:

Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Safety and feasibility of oral panobinostat in combination with cisplatin and pemetrexed [ 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) ] [ Designated as safety issue: Yes ]
    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.

Secondary Outcome Measures:
  • Maximum-tolerated dose as assessed by NCI CTCAE, Version 4.0 [ Time Frame: 3 week cycle; the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: Yes ]
    Determination of maximum tolerated dose (MTD) will be based on cycle 1 toxicities

  • Dose-limiting toxicities and toxicity profile as assessed by NCI CTCAE, Version 4.0 [ Time Frame: 3 week cycle; the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: Yes ]
    Dose-limiting toxicity (DLT) will be based on cycle 1 toxicities.

  • Exploratory biomarker analysis [ Time Frame: Blood specimens will be collected prior to treatment, prior to Cycles 2-6. In addition, a blood specimen will be collected if the patient is removed from the study due to progression of disease. the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: No ]
    Molecular markers predictive for response to panobinostat remain unknown. This trial offers the opportunity to retrospectively study biomarkers and their association with clinical outcomes.

  • Efficacy of oral panobinostat in combination with cisplatin/pemetrexed in an expanded cohort of patients with NSCLC [ Time Frame: CT scans will be performed at baseline and every two cycles; the expected time frame is 18 weeks (or 6 cycles) ] [ Designated as safety issue: No ]
    Response rate will be assessed by CT scan. CT scans will be performed at baseline and every two cycles. The evaluation of response will be based on standard RECIST criteria.

Estimated Enrollment: 28
Study Start Date: April 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I dose-escalation
Drug: panobinostat Drug: cisplatin Drug: pemetrexed Other: Biomarker studies
Drug: Panobinostat, Cisplatin, Pemetrexed

Drug: Panobinostat Oral (by mouth) once daily every Monday, Wednesday, and Friday for the first two weeks of each three week cycle (as per dose escalation schedule (dose levels 1 and 2: AUC 5; dose levels 3 and 4: AUC 6). Number of cycles: 6 maximum.

Drug: Cisplatin IV (in the vein) on day 1 of a 21-day cycle Number of cycles: 6 maximum. Drug: Pemetrexed IV (in the vein) on day 1 of a 21-day cycle Other: Correlative studies Biomarker Analysis: blood collected pre-study and Cycles 2-6, Day 1.

Other Names:
  • LBH-589
  • Platinol
  • Almita

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 whole.
  • 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 months).
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01336842

United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
University of California, Davis
Novartis Pharmaceuticals
Principal Investigator: David Gandara, MD University of California, Davis
  More Information

No publications provided

Responsible Party: University of California, Davis Identifier: NCT01336842     History of Changes
Other Study ID Numbers: UCDCC#220
Study First Received: April 11, 2011
Last Updated: December 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Davis:
dose escalation

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on March 03, 2015