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

NCT03437070 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 20170991
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Leiomyosarcoma

Keywords

Advanced Leiomyosarcoma; Recurrent Leiomyosarcoma

Outcome Measures

Primary Outcomes (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).

  About 21 days, one cycle of protocol therapy

Secondary Outcomes (2)

• Toxicity in Study Participants

  Up to 8 months

• Clinical Benefit Rate in Study Participants

  From Baseline to End of Treatment, up to 8 months

Study Arms (1)

TDO Dose Level

EXPERIMENTAL

Trabectedin \[T\], Doxorubicin \[D\], and Olaratumab \[O\]

Drug: Trabectedin; Drug: Doxorubicin; Drug: Olaratumab

Interventions

Trabectedin DRUG

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

Also known as: Yondelis

TDO Dose Level

Doxorubicin DRUG

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

Also known as: Doxorubicin Hydrochloride

TDO Dose Level

Olaratumab DRUG

Administered intravenously per protocol

Also known as: Lartruvo

TDO Dose Level

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Miami: lead
• Janssen Scientific Affairs, LLC: collaborator

MeSH Terms

Conditions

Leiomyosarcoma

Interventions

Trabectedin; Doxorubicin; olaratumab

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Marilyn Huang, MD, MS

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Dose escalation

Study Record Dates

• First Submitted: February 10, 2018
• First Posted: February 19, 2018
• Study Start: June 1, 2019
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2023
• Last Updated: March 18, 2019

Record last verified: 2019-03