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PTCLPhase 1NCT02757248

Ph1 Volasertib Plus Romidepsin in R/R PTCL and CTCL

A Phase 1 study testing Volasertib and Romidepsin in people with PTCL and CTCL, run by Anne Beaven, MD.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a phase I study of the combination of volasertib and romidepsin in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) or stage IIB-IV cutaneous T cell lymphoma (CTCL). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
PTCL, CTCL
What is being tested?
Volasertib and Romidepsin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Nov 2016to Nov 2016
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

  • A) Patients with a relapsed/refractory peripheral T cell lymphoma. Patients must have received at least one prior standard cytotoxic regimen such as CHOP or EPOCH OR B) Patients with relapsed/refractory stage IIb-IV cutaneous T cell lymphoma who have received at least one standard systemic treatment such as extracorporeal photopheresis, bexarotene or interferon.
  • Age > 18 years old
  • Eastern Cooperative Oncology Group performance status of <2
  • Evidence of measurable or evaluable disease
  • Patients must have recovered from all clinically relevant toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03). Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
  • Platelets >100 x 109/L
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  • ANC>1.5 x 109/L
  • AST/ALT <3.0 x institutional ULN, except for people with liver involvement by their lymphoma, who may be included if AST/ALT <5 x ULN.
  • Total Bilirubin < 1.5 x ULN, except for patients with gilbert's syndrome who may be included if total bilirubin < 3.0 x ULN and direct bilirubin < 1.5 x ULN
  • The following laboratory values must be greater than the lower limits of normal prior to starting study drug (supplementation allowed): potassium, magnesium
  • Calculated or measured CrCl> 30ml/min (Appendix: 3)
  • Ability to provide written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.

Who cannot join

  • Prior Treatment:
  • Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks prior to the start of study drug. However, if they have received nitrosurea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received.
  • No limitations to number of prior therapies.
  • Prior treatment with volasertib or any PLK1 inhibitor
  • Prior treatment with a histone deacetylase inhibitor (anti-epileptics ok)
  • Active, uncontrolled, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
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  • Known HIV infection.
  • Active or chronic hepatitis B infection.
  • Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months.
  • Pregnant or breast feeding. Treatment under this protocol would expose an unborn child to significant risks.
  • Women and men of reproductive potential who are unwilling or unable to use an effective means of birth control during the study and for 3 months after receiving study drug.
  • Major surgery within the four weeks prior to initiating protocol therapy.
  • Diagnosis or treatment for any malignancy other than NHL within the 3 years preceding Day 1 of the protocol therapy. Exceptions are:
  • Basal or squamous cell carcinoma of the skin
  • In situ malignancy that has been completely resected.
  • Prostate cancer that was treated with prostatectomy or radiotherapy over 2 years before Day 1 of protocol therapy and whose PSA is undetectable.
  • Treatment with another investigational agent currently or within 21 days prior to enrollment. Patients may participate in other non-treatment studies concurrently if it will not interfere with participation in this study.
  • Myocardial infarction or unstable angina within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • QTcF>470msec using the Fredericia formula.
  • Known hypersensitivity to the trial drugs (volasertib and romidepsin)
  • Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with study drug and for the duration of participation (see Appendix 2 Tables):
  • Medication with a significant known risk of prolonging the QT interval or inducing Torsades de Pointes (please refer to http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm)
  • Strong inhibitors or strong inducers of CYP3A4/5 (please refer to http://medicine.iupui.edu/flockhart/table.htm or http://www.druginteractioninfo.org)
  • Herbal supplements

About this study

Official title: A Phase I Trial of Volasertib Plus Romidepsin in Patients With Relapsed/Refractory Peripheral T Cell and Cutaneous T Cell Lymphoma

This is a phase I study of the combination of volasertib and romidepsin in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) or stage IIB-IV cutaneous T cell lymphoma (CTCL). This study will determine the maximum tolerated dose (MTD) of this combination by treating cohorts of patients at a certain dose combination. The investigators will use a Bayesian design to determine the dose combination for the next cohort of patients and to determine the MTD. Overall response rate as well as adverse events will be monitored and reported.

Read the detailed description

This is a non-randomized, unblinded single arm Phase I multi-center trial to determine the maximum tolerated dose (MTD) of the combination of volasertib and romidepsin in patients with relapsed/refractory peripheral T cell (PTCL) and cutaneous T cell (CTCL) lymphoma.

Primary Objectives:

  1. Determine the maximum tolerated dose (MTD) of the combination of romidepsin and volasertib in patients with relapsed/refractory peripheral T cell and cutaneous T cell lymphoma.

Secondary Objectives:

  1. Evaluate the overall response rate (ORR) to the combination of romidepsin and volasertib in patients with relapsed/refractory peripheral T cell and cutaneous t cell lymphoma.
  2. Define gene expression signatures and patterns of acquired tumor mutations that dynamically correlate to clinical response to romidepsin/volasertib combination therapy in cutaneous T cell lymphoma (CTCL) through longitudinal RNA sequencing of tumor samples.

Dose Combinations

(-1): Volasertib 50mg/m2 Days 1 \& 8; Romidepsin 10mg/m2 Days 1, 8 \& 15

(1-starting dose): Volasertib 75mg/m2 Days 1 \& 8; Romidepsin 12mg/m2 Days 1, 8 \& 15 (2): Volasertib 100mg/m2 Days 1 \& 8; Romidepsin 12mg/m2 Days 1, 8 and 15 (3): Volasertib 100mg/m2 Days 1 \& 8; Romidepsin 14mg/m2 Days 1, 8 and 15 (4): Volasertib 150mg/m2 Days 1 \& 8; Romidepsin 14mg/m2 Days 1, 8 and 15

Each cycle is 28 days Each drug is given intravenously

Conditions
PTCL, CTCL
Being tested
Volasertib, Romidepsin

What participants receive

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

  • VolasertibDrug

    Volasertib 75-150mg/m2 given intravenously on days 1 and 8

  • RomidepsinDrug

    Romidepsin 12-14mg/m2 given intravenously on days 1, 8 and 15

Study groups in NCT02757248
Study groupRoleWhat they receive
Cohort 1ExperimentalVolasertib 75mg/m2 on days 1 and 8 Romidepsin 12mg/m2 on days 1, 8 and 15
Receives: Drug: Volasertib; Drug: Romidepsin
Cohort 2ExperimentalVolasertib 100mg/m2 on days 1 and 8 Romidepsin 12mg/m2 on days 1, 8 and 15
Receives: Drug: Volasertib; Drug: Romidepsin
Cohort 3ExperimentalVolasertib 100mg/m2 on days 1 and 8 Romidepsin 14mg/m2 on days 1, 8 and 15
Receives: Drug: Volasertib; Drug: Romidepsin
Cohort 4ExperimentalVolasertib 150mg/m2 on days 1 and 8 Romidepsin 14mg/m2 on days 1, 8 and 15
Receives: Drug: Volasertib; Drug: Romidepsin
Cohort -1ExperimentalVolasertib 50mg/m2 on days 1 and 8 Romidepsin 10mg/m2 on days 1, 8 and 15
Receives: Drug: Volasertib; Drug: Romidepsin

What is being measured

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

  1. Maximum Tolerated Dose

    Determine the maximum tolerated dose (MTD) of the combination of romidepsin and volasertib in patients with relapsed/refractory peripheral T cell and cutaneous T cell lymphoma.

    Measured: 12 months or until 2 DLTs are experienced in a cohort

Secondary outcomes (3)

  1. Overall Response Rate

    Evaluate the overall response rate (ORR) to the combination of romidepsin and volasertib in patients with relapsed/refractory peripheral T cell and cutaneous t cell lymphoma.

    Measured: 24 months

  2. Gene Expression Signature

    Define 1) genes expressed at significantly different levels (using linear analysis or the Wilxocon rank sum test and p< 0.05 as significance threshold) in tumor biopsies taken before treatment from patients exhibiting a clinical response versus non-responders to romidepsin/volasertib by analysis of levels of mRNA gene transcription by mRNA whole transcriptome sequencing (RNA-seq) Comparison of baseline to interim 8 week biopsy samples will be used to define changes in gene expression induced by combination treatment. These will be derived for each patient by using paired T tests for RNA sequencing FPKM values with correction for multiple comparisons via FDR calculation by the Benjamini-Hochberg method (a cutoff of FDR < 0.05 will be used to define genes included in the treatment gene signature).

    Measured: 60 months

  3. Gene Mutation Analysis

    Define 2) and 2) define mutations associated with primary (lack of clinical response) or acquired resistance (relapse or loss of response after first clinical response) to romidepsin/volasertib by analysis of tumor genetic sequences by using RNA-seq metholodies on tumor samples taken before or after treatment with romidepsin/volasertib and analysis of paired normal DNA sequence(s). Mutations for relapse samples will be obtained by comparing transcriptome profiles before and after development of resistance to romidepsin/volasertib. Specifically, we will assess whether individual genes become mutated at relapsed in a recurrent fashion (in 2 or more patients in the cohort).

    Measured: 60 months

Timeline

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

  1. First posted2 May 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionNov 2016
  4. Study completionNov 2016

Why it stopped: Boehringer Ingelheim is discontinuing their volasertib development program

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02757248
Sponsor's protocol ID
Pro00060068
Status last verified
Nov 2016
First submitted
22 Mar 2016
Last updated
1 Dec 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Volasertib and Romidepsin in people with PTCL and CTCL, run by Anne Beaven, MD.

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 13 inclusion and 24 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 1 Dec 2016. 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?

Maximum Tolerated Dose (time frame: 12 months or until 2 DLTs are experienced in a cohort). 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 NCT02757248.

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 1 Dec 2016.

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