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Metastatic SarcomaPhase 2NCT02448537

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

A Phase 2 study testing PM01183, Doxorubicin and Gemcitabine in people with Metastatic Sarcoma, run by Massachusetts General Hospital at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic Sarcoma
What is being tested?
PM01183, Doxorubicin and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
2 sitesUnited States
Study dates
Aug 2015to 1 Apr 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to receiving study agents.
  • For patients in stratum A, an echocardiogram or multiple gated acquisition scan (MUGA) demonstrating left ventricular ejection fraction > 50% is required within 30 days prior to study drug administration.
  • Participants must be willing and able to comply with the study scheduled visits, laboratory tests, and other procedures outlined in the protocol.
  • Pre-menopausal women must have a negative pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant, double barrier and/or complete abstinence (non-periodic).
  • Washout period prior to Day 1 Cycle 1:
  • ≥ 3 weeks since last chemotherapy or therapeutic radiation therapy (RT)
  • ≥ 4 weeks or 3 half-lives since prior antibody-based therapy, whichever is shorter
  • ≥ 2 weeks since any oral anti-neoplastic or oral investigational agent
  • Resolution of treatment-related toxicity to ≤ grade 1; alopecia and cutaneous toxicity are allowed ≤ grade 2.
  • ≥1 week since palliative RT
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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
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  • 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.
  • Immunocompromised patients, including those with HIV.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

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.

Read the detailed description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

PM01183 is a new drug that is believed to bind DNA cause double strands of DNA to break. This drug has been studied in previous research studies, and these suggest that it may slow or stop the growth of cancers. The FDA (the U.S. Food and Drug Administration) has not approved PM01183 as a treatment for any disease.

In this research study, the investigators are trying to assess the effects, good or bad, that PM01183, administered either alone or in combination with gemcitabine or doxorubicin has on metastatic or unresectable sarcoma.

Being tested
PM01183, Doxorubicin, Gemcitabine
Keywords
Metastatic Sarcoma, Unresectable Sarcoma, PM01183
Medical subject headings
Sarcoma

What participants receive

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

  • PM01183Drug

    Also called lurbinectedin

  • DoxorubicinDrug

    Also called Hydroxydaunomycin Hydrochloride, Adriamycin, Hydroxydoxorubicin Hydrochloride

  • GemcitabineDrug

    Also called Gemzar

Study groups in NCT02448537
Study groupRoleWhat they receive
PM01183 and DoxorubicinExperimentalAnthracycline-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
Receives: Drug: PM01183; Drug: Doxorubicin
PM01183 and GemcitabineExperimentalPrior 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
Receives: Drug: PM01183; Drug: Gemcitabine
Single Agent PM01183ExperimentalPatients who have received at least both prior anthracycline and prior gemcitabine -PM01183 predetermined dose once via IV per cycle
Receives: Drug: PM01183

What is being measured

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

  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.

    Measured: 24 Weeks

Secondary outcomes (2)

  1. Overall Response Rate

    The overall response rate is the number of participants that achieved either Stable Disease (SD), a Partial Response (PR), or a Complete Response (CR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The overall response rate is the best response recorded from the start of treatment until disease progression/recurrence.

    • Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
    • 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.

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

  2. Treatment Related Serious Adverse Events

    Summary of the serious adverse events (SAE) experienced by participants that were deemed to be at least possibly related to PM01183 when administered alone or with Doxorubicin or Gemcitabine. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE v4).

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

Timeline

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

  1. First posted19 May 2015 (estimated)
  2. Study startAug 2015
  3. Primary completionFeb 2017
  4. Study completion1 Apr 2019

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02448537
Sponsor's protocol ID
15-083
Status last verified
Feb 2021
First submitted
15 May 2015
Last updated
3 Mar 2021
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31896519

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PM01183, Doxorubicin and Gemcitabine in people with Metastatic Sarcoma, run by Massachusetts General Hospital at 2 sites in United States.

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 26 inclusion and 16 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: finished, as of the sponsor's last update on 3 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Disease Control Rate (time frame: 24 Weeks). 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 NCT02448537, which also lists 1 linked publication.

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 3 Mar 2021.

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