Safety, Tolerability, and Efficacy of Doxorubicin and Pembrolizumab for Sarcoma

NCT03056001 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB0008134200020377LCI-SAR-STS-PEM-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of doxorubicin in combination with pembrolizumab in subjects with metastatic or unresectable soft tissue sarcoma. Based on previous studies, pembrolizumab may be an effective study treatment.

Conditions

Soft Tissue Sarcoma, Adult; Soft Tissue Sarcoma, Child

Outcome Measures

Primary Outcomes (1)

• Number of Participants With at Least One Severe or Life-Threatening Adverse Event

  Severe or life-threatening adverse events will be determined for each subject as a binary variable indicating whether or not the subject experienced at least one adverse event that meets the following criteria: is considered a serious adverse event (per CFR 21 Part 312), is study treatment related per the Sponsor-Investigator, and considered to be clinically significant by the Sponsor-Investigator. An adverse event will be considered study treatment related if it is determined that the event is at least possibly related to either pembrolizumab, doxorubicin, or both.

  From enrollment to at least 90 days following cessation of study treatment. The median time on treatment was 5.8 months.

Secondary Outcomes (4)

• Overall Survival (OS)

  From treatment start to date of death, or censored as described; assessed for approximately 5 yrs or until censoring rate for entire study reduced to 20%, whichever occurred first. When the censoring rate reached 20%, OS time ranged from 0.1 - 4.8 yrs.

• Progression-free Survival (PFS)

  From treatment start date to date of progression/death, or censored as described; assessed for approximately 2 years.

• Number of Subjects With an Objective Response

  From enrollment to best response while on study treatment; subjects remained on treatment until disease progression or death or unacceptable toxicity (subjects were on treatment for a median of 5.8 months)

• Duration of Response (DoR)

  From date of response to date of progression/death, or censored as described above; assessed for approximately 2 years.

Study Arms (1)

Pembrolizumab + doxorubicin

EXPERIMENTAL

Participants will receive pembrolizumab IV infusion and doxorubicin IV injection on Day 1 of every 21 (+/- 3) days

Drug: Pembrolizumab; Drug: Doxorubicin

Interventions

Pembrolizumab DRUG

IV infusion on day 1 of each 3 week cycle, at dose of 200 mg

Also known as: KEYTRUDA®

Pembrolizumab + doxorubicin

Doxorubicin DRUG

IV injection on day 1 of each 3 week cycle, starting at dose of 60 mg/m2 (may be escalated to 75 mg/m2 per investigator discretion after Cycle 1)

Also known as: Adriamycin

Pembrolizumab + doxorubicin

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Must have a histologically confirmed diagnosis of unresectable or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy. Patients with Ewings sarcoma, osteosarcoma, chondrosarcoma, Kaposis sarcoma, gastrointestinal stromal tumors (GIST), clear cell sarcoma, alveolar soft part sarcoma and any other soft tissue or bone sarcoma felt to be chemotherapy resistant in the opinion of the Sponsor-Investigator will be excluded.
• Must not have received prior treatment with an anthracycline chemotherapy (eg, doxorubicin) and/or anti-PD-1/PD-L1 therapy.
• May have had any number of prior systemic cytotoxic therapies for unresectable/metastatic disease.
• Must have at least one radiologically measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter or lymph node that is 15mm in short axis imaged by CT scan or MRI. Tumors with previously irradiated field will be designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence of at least 90 days following completion of radiotherapy.
• All subjects with accessible tumor will be asked to provide a fresh tumor biopsy if they can be safely biopsied in the opinion of the investigator. Recently obtained archived core or excisional biopsy of a tumor lesion (obtained up to 12 months prior to Cycle 1 Day 1) may be substituted only if the subject is unwilling or unable (e.g. inaccessible or subject safety concern) to undergo a fresh tumor biopsy. Subjects who are unwilling or unable to have a fresh tumor biopsy and do not have recently obtained archived tissue available may submit an archived specimen (obtained \> 12 months prior to Cycle 1 Day 1) only upon approval from the Sponsor-Investigator.
• Be at least 12 years of age on day of signing informed consent. Assent will be obtained in appropriately aged subjects per institutional guidelines.
• ECOG performance status 0 or 1.
• Life expectancy of at least 3 months per the Investigator.
• Have adequate organ function as indicated by the laboratory values in Table 1 of protocol. All screening labs should be performed within 10 days of treatment initiation. PT/INR and PTT must be performed within 7 days of study treatment initiation for subjects on anti-coagulants such as coumadin/heparin.
• The subject has left ventricular ejection fraction (LVEF) greater than or equal to 50% assessed within 21 days prior to study regimen initiation.
• Subjects must not be expecting to conceive or father children within the timeframe referenced below. Subjects of childbearing potential must be willing to adhere to the contraception requirement as described in Section 3.3.2 from the day of the screening visit (or 14 days prior to the initiation of study treatment for oral contraception) throughout the study period up to 120 days after the last dose of pembrolizumab and/or up to 180 days after the last dose of doxorubicin. If there is any question that a subject of childbearing potential will not reliably comply with the requirements for contraception, that subject should not be entered into the study.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test at screening (within 72 hours of first dose of study treatment). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible.
• Subject has voluntarily agreed to participate by giving written informed consent for the trial. The subject may also provide consent for Optional and Future Studies-Biospecimen Collection. However, the subject may participate in the main trial without participating in Optional and Future Studies.

You may not qualify if:

• Currently participating and receiving study therapy or have participated in a study of an investigational agent and received study therapy or used an investigational device within 30 days of the first dose of study regimen.
• Have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study regimen.
• Have a known history of active TB (Bacillus Tuberculosis).
• Have had a prior anti-cancer monoclonal antibody (mAb) given to treat malignancy within 4 weeks prior to the first dose of study regimen or have not recovered (i.e. less than or equal to Grade 1 or at baseline) from adverse events due to previous mAbs.
• Have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first dose of study regimen or who have not recovered (i.e. less than or equal to Grade 1 or at baseline) from adverse events due to previous chemotherapy, targeted small molecule therapy, or radiation therapy.
• Note: Subjects with less than or equal to Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subjects have received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy as determined by the Investigator.
• Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study regimen and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to the first dose of the study regimen. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Have known history of, or any evidence of active, non-infectious pneumonitis.
• Have an active infection requiring systemic therapy (uncomplicated urinary tract infection treated with oral antibiotics is permitted).
• Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subjects participation for the full duration of the trial, or is not in the best interest of the subjects to participate, in the opinion of the treating Investigator.
• Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as determined by the Investigator.
• Are pregnant or breastfeeding

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Links

• Search clinical trials at Levine Cancer Institute.

MeSH Terms

Conditions

Sarcoma

Interventions

pembrolizumab; Doxorubicin

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

Results Point of Contact

• Title: Chair of Biostatistics Department
• Organization: Levine Cancer Institute

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Megan Jagosky, MD

  Levine Cancer Institute, Atrium Health (formerly Carolinas HealthCare System)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: February 16, 2017
• Study Start: May 1, 2017
• Primary Completion: November 16, 2021
• Study Completion: November 15, 2022
• Last Updated: November 18, 2023
• Results First Posted: February 8, 2023

Record last verified: 2023-10

Locations

US (1)