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LeiomyosarcomaPhase 1NCT03437070

Trabectedin, Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma

A Phase 1 study testing Trabectedin, Doxorubicin and Olaratumab in people with Leiomyosarcoma, run by University of Miami.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study seeks to determine if addition of trabectedin (T) to combination doxorubicin (D) and olaratumab (O), is feasible and tolerable with antitumor activity in metastatic or recurrent Leiomyosarcomas (LMS) patients who have limited therapeutic options. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leiomyosarcoma
What is being tested?
Trabectedin, Doxorubicin and Olaratumab
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
Jun 2019to Jun 2023
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

  • Histologically confirmed metastatic, advanced, or recurrent, LMS. Note: Patients should have tissue, either archival or fresh biopsy, submitted for pathologic review to confirm diagnosis of LMS. For patients with recurrent disease with disease free interval greater than six months, a fresh biopsy must be obtained.
  • All patients with recurrent or metastatic LMS deemed unresectable must have measurable disease as defined by RECIST 1.1.
  • All patients with advanced LMS may be enrolled after an initial cytoreductive surgery if there is measurable disease as defined by RECIST 1.1.
  • Life expectancy greater than 3 months.
  • Male or female, age ≥18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1.
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  • Resolution of clinically significant toxic effects of prior surgery, radiotherapy or systemic anticancer therapy.
  • Patients must not have received prior doxorubicin chemotherapy; only 1 prior chemotherapy line allowable and must be discontinued at least 4 weeks prior to first day of study treatment.
  • Patients should be free of active infections requiring antibiotics (with exception of urinary tract infection).
  • Patients must have adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) ≥1,500 cells/mm³
  • Platelet count ≥100,000/mm³
  • Hemoglobin ≥9.0g/dL
  • Total bilirubin <1.0 upper limit of normal (ULN)
  • Alkaline phosphatase of non-osseous origin ≤ 2.5 x ULN
  • Aminotransferase (AST and ALT) ≤ 2.5 x ULN
  • Creatinine phosphokinase (CPK) ≤ 2.5 x ULN
  • Isotope Dilution Mass Spectrometry (IDMS) creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 40 mL/min
  • Albumin ≤ 3 g/dL*
  • *Hypoalbuminemia < 3 g/dL should be considered carefully but in and of itself, not exclusionary.
  • Women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until 3 months for women and 5 months for men after completion of study drug administration. WOCBP must have a negative serum or urine test at time of enrollment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study therapy, and 5 months after completion of study drug administration.
  • Patients must have adequate cardiac function (ejection fraction ≥ 45%) to receive therapy.
  • Ability to understand the investigational nature, potential risks and benefits of the research study and to provide valid written informed consent.

Who cannot join

  • Patients without histologically confirmed LMS
  • Patients without measurable disease by RECIST 1.1 criteria
  • Prior doxorubicin, trabectedin, or olaratumab chemotherapy
  • Patients with an ECOG of 2, 3 or 4 (Appendix C)
  • Patient with known allergies to pegfilgrastim/filgrastim.
  • Patients with known active central nervous system (CNS) metastasis and/or carcinomatous meningitis.
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  • Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study therapy and during the study.
  • Patients with a known sensitivity to humanized antibodies or sensitivity attributed to compounds of similar chemical or biological composition to alkylating agents or anthracyclines.
  • A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec.
  • Patients on combination antiretroviral therapy are ineligible.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infections (including viral hepatitis), decompensated cirrhosis or chronic liver disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.
  • Adults unable to consent, pregnant or nursing women or prisoners.
  • Any serious medical or psychiatric illness/condition likely in the judgment of the Investigator(s) to interfere or limit compliance with study requirements/treatment.
  • Diagnosis of another primary malignancy within the past 5 years with the exception of non-melanoma skin cancer.
  • Patients with a prior history of grade 3 capillary leak syndrome (CLS) or <grade 3 CLS with pulmonary involvement.
  • Unwilling to abstain from alcohol ingestion for duration of the study
  • Patients with elevated liver function or bilirubin not meeting criteria for treatment

About this study

Official title: A Phase I Study of Trabectedin in Combination With Fixed Doses of Doxorubicin and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma

This study seeks to determine if addition of trabectedin (T) to combination doxorubicin (D) and olaratumab (O), is feasible and tolerable with antitumor activity in metastatic or recurrent Leiomyosarcomas (LMS) patients who have limited therapeutic options.

Read the detailed description

This is a traditional 3+3 phase I trial design to identify the recommended phase II dose (RP2D) of Trabectedin [T] that can be used in combination with Doxorubicin [D] and Olaratumab [O] for the treatment of patients with advanced stage or recurrent LMS.

Patients will be treated at an assigned dose level of combination therapy per dose escalation design.

Conditions
Leiomyosarcoma
Being tested
Trabectedin, Doxorubicin, Olaratumab
Keywords
Advanced Leiomyosarcoma, Recurrent Leiomyosarcoma
Medical subject headings
Leiomyosarcoma

What participants receive

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

  • TrabectedinDrug

    Also called Yondelis

    Administered intravenously per protocol on Day 1 for 21-day cycles.

  • DoxorubicinDrug

    Also called Doxorubicin Hydrochloride

    Administered intravenously per protocol on Day 1 for 21-day cycles.

  • OlaratumabDrug

    Also called Lartruvo

    Administered intravenously per protocol

Study groups in NCT03437070
Study groupRoleWhat they receive
TDO Dose LevelExperimentalTrabectedin [T], Doxorubicin [D], and Olaratumab [O]
Receives: Drug: Trabectedin; Drug: Doxorubicin; Drug: Olaratumab

What is being measured

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

  1. Recommended Phase 2 Dose (RP2D) of Trabectedin in Combination with Doxorubucin and Olaratumab

    Determination of the recommended phase 2 dose (RP2D) of Trabectedin [T] to be used in combination with Doxorubicin [D] and Olaratumab [O] for the treatment of patients with metastatic or recurrent LMS. Patients will be treated at one of 4-6 dose levels according to the standard dose escalation/de-escalation scheme. In accordance with this scheme, the RP2D of TDO will be established as the highest dose level tested for which no more than 2 out of 12 patients experiences dose-limiting toxicity (DLT).

    Measured: About 21 days, one cycle of protocol therapy

Secondary outcomes (2)

  1. Toxicity in Study Participants

    Determination of the safety, tolerability, and toxicity profile of administering TDO in metastatic or recurrent LMS patients, including assessment of dose-limiting toxicities (DLTs).

    Measured: Up to 8 months

  2. Clinical Benefit Rate in Study Participants

    Clinical benefit rate (CBR), as defined by best response, (Complete Response (CR), Partial Response (PR) or Stable Disease (SD)) will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1.

    Measured: From Baseline to End of Treatment, up to 8 months

Timeline

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

  1. First posted19 Feb 2018
  2. Study startJun 2019 (estimated)
  3. Primary completionJun 2021 (estimated)
  4. Study completionJun 2023 (estimated)

Why it stopped: Sponsor Decision

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
Model description
Dose escalation
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03437070
Sponsor's protocol ID
20170991
Status last verified
Mar 2019
First submitted
10 Feb 2018
Last updated
18 Mar 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trabectedin, Doxorubicin and Olaratumab in people with Leiomyosarcoma, run by University of Miami.

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 22 inclusion and 17 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 18 Mar 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?

Recommended Phase 2 Dose (RP2D) of Trabectedin in Combination with Doxorubucin and Olaratumab (time frame: About 21 days, one cycle of protocol therapy). 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 NCT03437070.

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 18 Mar 2019.

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