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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02448537
Recruitment Status : Active, not recruiting
First Posted : May 19, 2015
Results First Posted : March 5, 2018
Last Update Posted : November 15, 2019
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
PharmaMar
Information provided by (Responsible Party):
Gregory Cote, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE May 15, 2015
First Posted Date  ICMJE May 19, 2015
Results First Submitted Date  ICMJE February 5, 2018
Results First Posted Date  ICMJE March 5, 2018
Last Update Posted Date November 15, 2019
Actual Study Start Date  ICMJE August 2015
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 5, 2018)
Disease Control Rate [ Time Frame: 24 Weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 15, 2015)
True Disease Control Rate [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 5, 2018)
  • Overall Response Rate [ Time Frame: Every 6 weeks for the first 8 cycles (cycle is 21 days) and then every 9 weeks thereafter until disease progression ]
    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.
  • Overall Survival Rate [ Time Frame: from the start of treatment until death ]
    Overall survival is measured as the median duration of time from the start of treatment until the time of death.
  • Treatment Related Serious Adverse Events [ Time Frame: From the start of treatment until 30 days after the end of treatment ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2015)
  • Overall Response Rate [ Time Frame: 26 weeks ]
  • Overall Survival Rate [ Time Frame: 24 months ]
  • Toxicity profile of PM01183 alone or with chemotherapy in this patient population [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas
Official Title  ICMJE A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Sarcoma
Intervention  ICMJE
  • Drug: PM01183
    Other Name: lurbinectedin
  • Drug: Doxorubicin
    Other Names:
    • Hydroxydaunomycin Hydrochloride
    • Adriamycin
    • Hydroxydoxorubicin Hydrochloride
  • Drug: Gemcitabine
    Other Name: Gemzar
Study Arms  ICMJE
  • Experimental: PM01183 and Doxorubicin

    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
    Interventions:
    • Drug: PM01183
    • Drug: Doxorubicin
  • Experimental: PM01183 and Gemcitabine

    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
    Interventions:
    • Drug: PM01183
    • Drug: Gemcitabine
  • Experimental: Single Agent PM01183

    Patients who have received at least both prior anthracycline and prior gemcitabine

    -PM01183 predetermined dose once via IV per cycle

    Intervention: Drug: PM01183
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 2, 2018)
42
Original Estimated Enrollment  ICMJE
 (submitted: May 15, 2015)
60
Estimated Study Completion Date  ICMJE February 2021
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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.
  • Immunocompromised patients, including those with HIV.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02448537
Other Study ID Numbers  ICMJE 15-083
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gregory Cote, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE
  • Dana-Farber Cancer Institute
  • PharmaMar
Investigators  ICMJE
Principal Investigator: Gregory Cote, MD PhD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP