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Renal CancerPhase 1NCT01005797

Study of Panobinostat in Combination With Sorafenib in Kidney, Soft Tissue or Lung Cancers

A Phase 1 study testing Panobinostat (LBH589), Sorafenib in people with Renal Cancer and Non Small Cell Lung Cancer (NSCLC), run by Medical University of South Carolina at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine if a new investigational drug called Panobinostat is safe, tolerable and to obtain an initial assessment of efficacy, when given in combination with Sorafenib for the treatment of certain types of lung cancer, kidney cancer and soft tissue sarcoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Panobinostat (LBH589), Sorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
Nov 2009to Jan 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients aged ≥ 18 years old
  • ECOG Performance Status of ≤ 2
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Part A (dose escalation): Histologically or cytologically documented metastatic renal cell carcinoma (RCC) of all histologic types, soft tissue sarcoma (STS) limited to the following histologies: angiosarcoma, liposarcoma, and leiomyosarcoma, or non-squamous non-small-cell lung carcinoma (NSCLC). Parts B (RCC) and C (NSCLC) and D (STS)(expanded cohorts). Patients with RCC must have progressive metastatic disease and received at least one multi-kinase inhibitor (e.g., sorafenib/Nexavar or sunitinib/Sutent), or an mTOR inhibitor (e.g., Temsirolimus). Patients with STS must have progressive disease and have received at least two therapeutic regimens (first-line, second-line treatments).
  • For patients with metastatic NSCLC, they must have received two standard therapeutic regimens (first-line and second-line treatments).
  • In Part A, evaluable disease by radiology and/or a recognized serum tumor marker is required. In Parts B, C, and D measurable disease by RECIST is required
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  • Predicted life expectancy ≥ 12 weeks
  • Patients may have had prior therapy, providing the following conditions are met:
  • Patients must have recovered from any treatment related toxicities (with the exception of alopecia) to ≤ CTC grade 1 (fatigue, and neurotoxicity at grade 2 are permissible if stable for >3 months) prior to registration.
  • Chemotherapy: A minimum of 5 predicted half-lives of the agent must have elapsed between the end of treatment and registration on to the study. When halflives are not available the principle of 2 weeks for once daily medications and 3 weeks for agents given less frequently will be adopted, but discussion with the principal investigator is recommended.
  • Radiation: Patients may have had prior radiation therapy that has not exceeded 25% of bone marrow reserve provided that they have recovered from the acute, toxic effects of radiotherapy prior to registration. A minimum of 7 days must have elapsed between the end of radiotherapy to non-target lesions and registration into the study (minimum of 28 days for target lesions).
  • Surgery: Previous surgery is permitted provided that wound healing has occurred prior to registration.
  • Patients must meet the following laboratory criteria:
  • Hematology:
  • Neutrophil count of >1500/mm3
  • Platelet count of > 100,000/mm3L
  • Hemoglobin ≥ 9 g/dL
  • Biochemistry:
  • 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 ≤ 2.0 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
  • Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN
  • Serum potassium ≥ LLN
  • Serum sodium ≥ LLN
  • Serum albumin ≥ LLN or 2.5 g/dl
  • Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
  • INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib/LBH589 and monitored at least weekly, or as defined by the local standard of care, until the INR is stable. LBH589 and sorafenib may elevate the INR in those on coumadin derivatives
  • Patients must be clinically euthyroid (patients may be on thyroid hormone replacement)'
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal
  • Supportive therapy including bisphosphonates is permissible. Previous use of myeloid and erythroid growth factor support is permissible, but not within 2 weeks of commencement of study. Primary prophylactic use of myeloid and erythroid growth factors is not permitted within the study, but intervention or secondary prophylaxis is permitted if instituted following the documentation of ≥ grade 3 neutropenia or ≥ grade 2 anemia (hemoglobin)
  • Patient must be accessible for repeat dosing and follow-up
  • 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

Who cannot join

  • NSCLC of squamous histology.
  • 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 LBH589 treatment
  • Known or suspected allergy to sorafenib or LBH589
  • Impaired cardiac function including any one of the following:
  • Screening ECG with a QTc > 450 msec prior to enrollment to the study
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  • 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 (bifasicular block)
  • Uncontrolled hypertension
  • Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
  • Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)
  • Patients with unresolved diarrhea > CTCAE grade 1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589
  • Other concurrent severe and/or uncontrolled medical conditions
  • Patients who have undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Concomitant use of any anti-cancer therapy or radiation therapy
  • 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
  • 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
  • Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
  • Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
  • Symptomatic brain metastases which are not stable, require steroids, or anti-epileptic medication.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Use of St. John's Wort or rifampin (rifampicin).
  • Any condition that impairs patient's ability to swallow whole pills.
  • Active or uncontrolled infections, or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study.
  • Any other condition, which in the investigator's opinion, would compromise the safety of the patient or the feasibility of completing the study objectives through the use of this patient.
  • Note: Investigators must ensure that the patients enrolled in the study will be available for all study procedures, including dosing, toxicity assessment and follow up and have the ability to understand the requirements of the study and provide signed informed consent.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Medical University of South Carolina Hollings Cancer Center

    Charleston, South Carolina, 29425

Other trials in United States

About this study

Official title: A Phase I Safety and Tolerability Study of LBH589 in Combination With Sorafenib in Patients With Advanced Renal Cell Carcinoma, Soft Tissue Sarcoma, and Non-small Cell Lung Carcinoma (NSCLC) of Non-squamous Histologies.

The purpose of this study is to determine if a new investigational drug called Panobinostat is safe, tolerable and to obtain an initial assessment of efficacy, when given in combination with Sorafenib for the treatment of certain types of lung cancer, kidney cancer and soft tissue sarcoma.

Being tested
Panobinostat (LBH589), Sorafenib
Keywords
Renal Cancer, Non Small Cell Lung Cancer (NSCLC), Solid Tumor, Soft tissue sarcoma, Sorafenib, Panobinostat
Medical subject headings
Kidney Neoplasms, Carcinoma, Non-Small-Cell Lung, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Panobinostat (LBH589), SorafenibDrug

    Starting dose of sorafenib: 400 mg bid on Day 1-28 of each 28-day cycle; of LBH589: 15 mg on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of each 28-day cycle. Administered simultaneously.

Study groups in NCT01005797
Study groupRoleWhat they receive
Expansion AExperimentalExpansion A -RCC cohort expansion phase at RP2D: Sorafenib bid daily continuously from cycle 1 (28 day cycle), LBH589 given on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of a 28 day cycle.
Receives: Drug: Panobinostat (LBH589), Sorafenib
Expansion BExperimentalExpansion B -NSCLC cohort expansion phase at RP2D: Sorafenib bid daily continuously from cycle 1 (28 day cycle), LBH589 given on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of a 28 day cycle.
Receives: Drug: Panobinostat (LBH589), Sorafenib
Expansion CExperimentalExpansion C -STS cohort expansion phase at RP2D: Sorafenib bid daily continuously from cycle 1 (28 day cycle), LBH589 on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26 of a 28 day cycle.
Receives: Drug: Panobinostat (LBH589), Sorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine maximum tolerated dose (MTD)for LBH 589 in combination with Sorafenib and establish a recommended phase 2 dose for each drug combination

    Measured: Point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1

Secondary outcomes (2)

  1. Evaluate the safety profile of LGB589 in combination with sorafenib, including DLTs

    Measured: During the first treatment period (i.e. 28 days) or toxicity similar to DLT after the initial 28-day treatment period

  2. Observe evidence of anti-cancer efficacy estimates of the combination in the tarted expanded cohorts.

    Measured: Evaluation of disease & re-evaluation for response

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Nov 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionMar 2014
  4. Study completionJan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01005797
Sponsor's protocol ID
101273
Other IDs
CLBH589BUS16T
Status last verified
Jan 2017
First submitted
30 Oct 2009
Last updated
3 Mar 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Panobinostat (LBH589), Sorafenib in people with Renal Cancer and Non Small Cell Lung Cancer (NSCLC), run by Medical University of South Carolina at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine maximum tolerated dose (MTD)for LBH 589 in combination with Sorafenib and establish a recommended phase 2 dose for each drug combination (time frame: Point in time when no more than 1 of 6 patients has a Dose Limiting Toxicity (DLT) in cycle 1). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01005797.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2017.

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