A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas

NCT02448537 | Completed Phase 2 Results DMC

• 1 other identifier: 15-083
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is investigating a drug called PM01183 alone and in combination with chemotherapy drugs called gemcitabine or doxorubicin as a possible treatment for metastatic or unresectable Sarcoma.

Conditions

Metastatic Sarcoma

Keywords

Metastatic Sarcoma; Unresectable Sarcoma; PM01183

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  The number of participants that achieved either Stable Disease (SD) or a Partial Response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 24 weeks. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. * Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  24 Weeks

Secondary Outcomes (2)

• Overall Response Rate

  Every 6 weeks for the first 8 cycles (cycle is 21 days) and then every 9 weeks thereafter until disease progression

• Treatment Related Serious Adverse Events

  From the start of treatment until 30 days after the end of treatment

Study Arms (3)

PM01183 and Doxorubicin

EXPERIMENTAL

Anthracycline-naïve patients will receive combination of PM01183 and Doxorubicin per cycle. * PM01183 predetermined dose daily via IV per cycle * Doxorubicin predetermined dose daily via IV per cycle

Drug: PM01183; Drug: Doxorubicin

PM01183 and Gemcitabine

EXPERIMENTAL

Prior anthracycline exposure and without prior gemcitabine exposure * PM01183 predetermined dose given twice via IV per cycle * Gemcitabine predetermined dose given twice via IV per cycle

Drug: PM01183; Drug: Gemcitabine

Single Agent PM01183

EXPERIMENTAL

Patients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle

Drug: PM01183

Interventions

PM01183 DRUG

Also known as: lurbinectedin

PM01183 and Doxorubicin; PM01183 and Gemcitabine; Single Agent PM01183

Doxorubicin DRUG

Also known as: Hydroxydaunomycin Hydrochloride, Adriamycin, Hydroxydoxorubicin Hydrochloride

PM01183 and Doxorubicin

Gemcitabine DRUG

Also known as: Gemzar

PM01183 and Gemcitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have pathologically confirmed soft-tissue sarcoma, which is metastatic or unresectable, sarcoma with no curative multimodality options
• Participants must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• No more than two prior lines of chemotherapy for metastatic sarcoma are allowed; Neo-adjuvant/adjuvant chemotherapy with definitive therapy (radiation, surgery or radiation and surgery) will not be counted as one of these prior lines of therapy.
• Age ≥ 18 and ≤ 75 years.
• Eastern Cooperative Oncology Group performance status ≤1 (see Appendix A)
• Life expectancy of greater than 3 months
• Participants must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 9 g/dl
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 100,000/mcL
• total bilirubin ≤ 1.5 X ULN
• AST(SGOT)/ALT(SGPT) ≤3 X ULN (including patients with liver metastases)
• creatinine ≤1.5 X ULN
• CPK \< 2.5 X ULN
• Albumin ≥ 3 g/dl

You may not qualify if:

• Prior exposure to PM01183
• Patients who have received trabectedin (Yondelis, ET-743) or participated in the phase III clinical study of trabectedin NCT01343277 previously will not be eligible.
• For stratum A, patients must not have received prior anthracycline-based therapy (prior treatment with non-anthracyclines is permitted).
• For stratum B patients must have received prior anthracycline-based therapy (or have a contraindication to receiving this treatment) and must not have received prior gemcitabine
• For stratum C, patients must have received prior anthracycline or gemcitabine-based therapy, or had a contraindication to either or both
• Prior radiation treatment of \>45 Gy to the pelvis
• Previously untreated Ewing Sarcoma and rhabdomyosarcoma
• Non-soft tissue sarcomas, such as osteosarcoma and chondrosarcoma are excluded
• Participants who are receiving any other investigational agents.
• Active hepatopathy of any origin including active hepatitis B and hepatitis C
• Participants with known uncontrolled brain metastases will be excluded from this clinical.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PM01183 or trabectedin (Yondelis, ET-743).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic indwelling drains, history of interstitial pneumonitis or pulmonary fibrosis or psychiatric illness/social situations that would limit compliance with study requirements.
• Actively breastfeeding women unless it is interrupted during treatment and at least 6 weeks after treatment discontinuation.
• Known myopathy or persistent CPK elevations \>2.5 ULN in two different determinations performed one week apart.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• PharmaMar: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Cote GM, Choy E, Chen T, Marino-Enriquez A, Morgan J, Merriam P, Thornton K, Wagner AJ, Nathenson MJ, Demetri G, George S. A phase II multi-strata study of lurbinectedin as a single agent or in combination with conventional chemotherapy in metastatic and/or unresectable sarcomas. Eur J Cancer. 2020 Feb;126:21-32. doi: 10.1016/j.ejca.2019.10.021. Epub 2019 Dec 31.

  PMID: 31896519 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

PM 01183; Doxorubicin; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Gregory Cote, M.D., Ph.D
• Organization: Massachusetts General Hospital

gcote@partners.org

617-724-4000

Study Officials

• Gregory Cote, MD PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: May 15, 2015
• First Posted: May 19, 2015
• Study Start: August 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: April 1, 2019
• Last Updated: March 3, 2021
• Results First Posted: March 5, 2018

Record last verified: 2021-02

Locations

US (2)