AzTrials
AzTrials

MelanomaPhase 1NCT03982134

PDR001 + Panobinostat for Melanoma and NSCLC

A Phase 1 study testing PDR001 and Panobinostat in people with Melanoma and Non Small Cell Lung Cancer, run by Muhammad Furqan.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The purpose of this research study is to find the dose of the study drug PDR001 that, when given in combination with the drug Panobinostat, results in the best outcomes for metastatic melanoma and non-small cell lung cancer (NSCLC) Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma, Non Small Cell Lung Cancer
What is being tested?
PDR001 and Panobinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Sep 2019to 1 May 2022
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

  • Patients eligible for inclusion in this study have to meet all of the following criteria:
  • Patients must provide written informed consent prior to any screening procedures.
  • Age 18 years or older.
  • Willing and able to comply with scheduled visits, treatment plan and laboratory tests
  • Able to swallow and retain oral medication Panobinostat
  • Histologically or cytologically confirmed diagnosis of melanoma or NSCLC
Show all 9Show fewer
  • ECOG performance status of 0-2
  • Patients with melanoma and NSCLC must have progressed clinically as determined by the treating physician on a prior line of anti-PD-1/PD-L1 therapy. If they have received more than one line of prior therapy, the last treatment must be with an anti-PD-1/PDL-1 inhibitor, alone or in combination with another systemic therapy (e.g. chemotherapy, CTLA4 inhibitor).
  • Patients with NSCLC who are known to have targetable genomic alterations (including EGFR exon 19 deletion or L858R substitution, ALK rearrangement, ROS1 fusion, NTRK 13 fusions, BRAF V600 mutation), must have progressed on or could not tolerate FDA approved targeted therapy for the alterations mentioned above, in addition to progressed on PD-1/L1 Checkpoint blockade to be eligible for the study. Patients with Melanoma who are known to have BRAF V600 mutation must have progressed on or could not tolerate BRAF-targeted therapy with or without MEK inhibitor in addition to PD-1/PD-L1 checkpoint inhibitor to be eligible for the study.

Who cannot join

  • Patients eligible for this study must not meet any of the following criteria:
  • Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the prior 2 weeks. Patients with residual symptoms that are either controlled or improving after treatment will be allowed to participate in the study.
  • History of severe hypersensitivity reactions to other mAbs
  • Prior treatment with an HDAC inhibitor
  • Patients who meet the following laboratory criteria:
  • Hematology:
Show all 46Show fewer
  • Neutrophil count of </=1500/mm3
  • Platelet count of </=100,000/mm3
  • Hemoglobin < 8 g/dL (Transfusion support is allowed to meet the eligibility)
  • Biochemistry:
  • AST/SGOT and ALT/SGPT >3 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
  • Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) </=40 mL/min
  • Impaired cardiac function or clinically significant cardiac disease, including any of the following:
  • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade >/= 2), uncontrolled hypertension or clinically significant arrhythmia
  • Corrected QT (QTcF) > 450 msec for males and females using Fridericia's correction on screening ECG or congenital long QT syndrome
  • Acute myocardial infarction or unstable angina pectoris < 3 months prior to study entry
  • Presence of any clinically significant cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality
  • Left Ventricular Ejection Fraction (LVEF) < 40%, as determined by echocardiogram (ECHO) or Multiple Gated acquisition (MUGA)
  • Subjects with active, known or suspected autoimmune disease requiring systemic immunosuppression. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • History of drug-induced pneumonitis
  • Active infection requiring systemic antibiotic therapy.
  • Known history of Human Immunodeficiency Virus (HIV) infection.
  • Known history of active HBV or HCV infection. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection.
  • Unresolved diarrhea ≥ CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
  • Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required systemic chemo or immunotherapy therapy (e.g. ductal carcinoma in situ, some low grade lymphomas, high-grade prostatic intraepithelial neoplasia, monoclonal gammopathy of undetermined significance); and completely resected carcinoma in situ of any type.
  • Any condition that would prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.
  • Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks is indicated as washout period. For patients receiving anticancer immunotherapies such as CTLA-4 antagonists, 3 weeks is indicated as the washout period
  • Patients requiring chronic treatment with systemic steroid therapy, other than replacement dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steroids are allowed.
  • Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above). Patients with prior history of allogeneic organ transplant will be excluded.
  • Use of any live vaccines within 4 weeks of initiation of study treatment.
  • Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery).
  • Patient who has received thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting the study treatment or patients who have not recovered from radiotherapy-related toxicities to CTCAE grade ≤1 (except alopecia and lymphopenia). For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs) radiotherapy ≤ 2 weeks prior to starting the study treatment or has not recovered from radiotherapy-related toxicities to CTCAE grade ≤1 (except alopecia and lymphopenia). Palliative radiotherapy for bone lesions ≤ 2 weeks prior to starting study treatment is allowed.
  • Participation in an interventional, investigational study within 2 weeks of the first dose of study treatment.
  • Presence of ≥ CTCAE grade 2 toxicity (except alopecia, regardless of grade), lymphopenia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior anti-cancer therapy.
  • Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF, M-CSF) ≤2 weeks prior start of study drug. An erythroid stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment.
  • Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150 days after the last dose of PDR001. Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient.
  • Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
  • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
  • Women are considered post-menopausal and not of child bearing potential if they have had over 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile age appropriate (e.g. generally 40-59 years), history of vasomotor symptoms (e.g. hot flushes) in the absence of other medical justification or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Sexually active males unless they use a condom during intercourse while taking the study treatment and for 150 days after stopping study treatment and should not father a child in this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the drug via seminal fluid.
  • Concomitant use of strong CYP3A4 inducers (Carbamazepine, Modafinil, Rifampin, Rifabutin, Rifapentin, Phenytoin, Phenobarbital and St. John's wort) or strong inhibitors like Cimetidine, Grapefruit juice and Seville oranges as mentioned in appendix E. If patient can come off of these drugs and receive an alternative therapy then they will be eligible as far as time equals 4 half-lives of that medication has elapsed prior to starting protocol therapy.

About this study

Official title: Phase Ib Study to Assess Safety and Tolerability of PDR001 in Combination With Panobinostat in Metastatic Melanoma and Non-small Cell Lung Cancer After Failure of Prior Anti PD1 or PD-L1 Therapy

The purpose of this research study is to find the dose of the study drug PDR001 that, when given in combination with the drug Panobinostat, results in the best outcomes for metastatic melanoma and non-small cell lung cancer (NSCLC)

Read the detailed description

This is an open label, non-randomized Phase Ib study combining PDR001 with HDAC inhibitor Panobinostat in patients with metastatic melanoma and NSCLC who have failed prior Anti PD1 or PD-L1 therapy.

The primary purpose of this study is to find the recommended Phase II dose (RP2D) of Panobinostat in combination with PDR001. Standard 3+3 design will be used for dose escalation or de-escalation. Depending upon tolerability and dosing, the total number of participants may vary from 9-24. Initially patients will start from dose level '0' and there will be 1 dose escalation level '1' and two de-escalation levels ('-1' and '-2'). The maximum number in each dose level will be 6.

Being tested
PDR001, Panobinostat
Medical subject headings
Melanoma, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • PDR001Drug

    Also called spartalizumab

    PDR001 is a humanized IgG4 antibody

  • PanobinostatDrug

    Also called LBH589 lactate

    Panobinostat is a Histone deacetylase inhibitor (HDACi).

Study groups in NCT03982134
Study groupRoleWhat they receive
PDR001 with PanobinostatExperimentalAll enrolled patients will be treated with a combination of PDR001 at 400mg every 4 weeks and panobinostat. Dose and frequency of Panobinostat will vary depending upon the dose-level cohort of the study participants. Each participant will be assigned to a particular dose-level cohort.
Receives: Drug: PDR001; Drug: Panobinostat

What is being measured

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

  1. To assess the safety and tolerability of PDR001 in combination with panobinostat in determining a recommended Phase II dose

    The recommended Phase 2 dose will be determined by using a 3 + 3 design with 1 dose escalation and 2 dose deescalation cohorts. Safety assessments will consist of monitoring and recording all adverse events, including serious adverse events, the monitoring of hematology, chemistry, ECG and the regular monitoring of vital signs, thyroid function, pregnancy and physical exam including weight and performance status.

    Measured: Initiation of treatment up to 2 years

Secondary outcomes (4)

  1. Incidence of dose limiting toxicities (DLTs) using CTCAE, Version 5.0

    All adverse events (AEs) will be considered in DLT assessment unless the event is clearly unrelated to trial treatment. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 will be used.

    Measured: Initiation of treatment up to 2 years

  2. Progression free survival (PFS) per RECIST 1.1

    PFS is defined as the time between the first dose of study therapy and the earliest date of progression or death (participants who have neither progressed nor dies will be censored at the most recent last-known-alive date).

    Measured: Initiation of treatment up to 2 years

  3. Overall survival (OS)

    OS is calculated from time when study therapy begins to death from any cause.

    Measured: Initiation of treatment up to 2 years

  4. Overall Response Rate (ORR) per RECIST 1.1

    OS is defined as the time between the first dose of study therapy and death (participants who have not died will be censored at the most recent last-known-alive date).

    Measured: Initiation of treatment up to 2 years

Timeline

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

  1. First posted11 Jun 2019
  2. Study startSep 2019 (estimated)
  3. Primary completion1 May 2021 (estimated)
  4. Study completion1 May 2022 (estimated)

Why it stopped: Sponsor decision to withdraw

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03982134
Sponsor's protocol ID
201904832
Status last verified
Oct 2019
First submitted
6 Jun 2019
Last updated
4 Oct 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PDR001 and Panobinostat in people with Melanoma and Non Small Cell Lung Cancer, run by Muhammad Furqan.

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 9 inclusion and 46 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: withdrawn, as of the sponsor's last update on 4 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

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 was withdrawn before enrolling participants, so there are no results.

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?

To assess the safety and tolerability of PDR001 in combination with panobinostat in determining a recommended Phase II dose (time frame: Initiation of treatment up to 2 years). 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 NCT03982134.

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 4 Oct 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in