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SarcomaPhase 1/2NCT02888665

Pembrolizumab and Doxorubicin Hydrochloride in Treating Patients With Sarcoma That is Metastatic or Cannot Be Removed by Surgery

A Phase 1/2 study testing Doxorubicin Hydrochloride, Laboratory Biomarker Analysis and Pembrolizumab in people with Sarcoma, run by Fred Hutchinson Cancer Center at 1 site 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 phase I/II trial studies the side effects and best dose of doxorubicin hydrochloride when given together with pembrolizumab and to see how well they work in treating patients with sarcoma that have spread to other parts of the body or that cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoma
What is being tested?
Doxorubicin Hydrochloride, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
1 siteUnited States
Study dates
5 Dec 2016to 9 Oct 2020
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to provide written informed consent/assent for the trial
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Have metastatic or unresectable sarcoma
  • Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Absolute neutrophil count (ANC) >= 1,500/mcL (within 10 days of treatment initiation)
  • Platelets >= 100,000/mcL (within 10 days of treatment initiation)
Show all 17Show fewer
  • Hemoglobin >= 9 g/dL (within 10 days of treatment initiation) or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (within 10 days of treatment initiation)
  • Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (within 10 days of treatment initiation)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (within 10 days of treatment initiation)
  • Albumin >= 2.5 mg/dL (within 10 days of treatment initiation)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days of treatment initiation)
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (within 10 days of treatment initiation)
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Ejection fraction > 45% by either multi-gated acquisition scan (MUGA) scan or echocardiogram

Who cannot join

  • Has prior treatment using an anthracycline
  • Has one of the following sarcoma subtypes where combining anthracyclines with other chemotherapies is established as the standard of care: osteosarcoma, Ewings sarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
Show all 23Show fewer
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent
  • Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Has 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
  • Has 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 trial treatment 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 trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has 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
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-programed death receptor 1 (PD-1), anti-PD-L1, anti-program death receptor ligand 2 (PD-L2) agent or anti-CTLA4
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy
  • Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Trial of Pembrolizumab in Combination With Doxorubicin as Treatment for Patients With Advanced Sarcomas

This phase I/II trial studies the side effects and best dose of doxorubicin hydrochloride when given together with pembrolizumab and to see how well they work in treating patients with sarcoma that have spread to other parts of the body or that cannot be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving doxorubicin hydrochloride together with pembrolizumab may work better in treating patients with sarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of the combination of pembrolizumab and doxorubicin hydrochloride (doxorubicin) in patients with advanced soft tissue sarcoma (STS).

II. To assess the clinical response rate of advanced soft tissue sarcoma (STS) patients receiving the combination of pembrolizumab and doxorubicin.

SECONDARY OBJECTIVES:

  1. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to time to response.

II. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to duration of response.

III. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to progression-free survival (PFS).

IV. To explore the clinical activity of pembrolizumab in subjects with advanced STS with respect to overall survival.

TERTIARY OBJECTIVES:

  1. To compare response rates between patients with high levels of PD-L1 expression with those who have PD-L1 absent.

OUTLINE: This is a phase I, dose-escalation study of doxorubicin hydrochloride followed by a phase II study.

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and doxorubicin hydrochloride IV over 1-3 hours on day 1 of courses 2-7 only. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

Conditions
Sarcoma
Being tested
Doxorubicin Hydrochloride, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Sarcoma

What participants receive

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

  • Doxorubicin HydrochlorideDrug

    Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02888665
Study groupRoleWhat they receive
Treatment (pembrolizumab, doxorubicin hydrochloride)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 and doxorubicin hydrochloride IV over 1-3 hours on day 1 of courses 2-7 only. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of Doxorubicin Hydrochloride Plus Pembrolizumab According to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) Version 4.0 (Phase I)

    Defined as a dose limiting toxicity (DLT) in less than 2 of 6 subjects. Only Phase 1 subjects will be evaluated for MTD.

    Measured: Up to 42 days (6 weeks)

  2. Objective Response Rate (ORR) (Phase II)

    Evaluated per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT. Complete Response (CR) is a complete elimination of the tumor; Partial Response (PR) is 30% reduction. If a subject experienced a PR, this was required to be confirmed with a second scan at the next appropriate cycle.

    Measured: Up to 2 years

Secondary outcomes (4)

  1. Duration of Response

    Duration of response is the mean time to progression for all subjects who responded.

    Measured: Up to 2 years

  2. Median Progression-free Survival (PFS)

    The Kaplan-Meier method will be used to estimate median PFS.

    Measured: Up to 2 years

  3. Overall Survival (OS)

    The Kaplan-Meier method will be used to estimate median OS.

    Measured: Up to 2 years

  4. Time to Response

    Average time to response

    Measured: Up to 2 years

Timeline

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

  1. First posted5 Sep 2016 (estimated)
  2. Study start5 Dec 2016
  3. Primary completion17 Mar 2020
  4. Study completion9 Oct 2020

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02888665
Sponsor's protocol ID
9624
Other IDs
NCI-2016-01286, 9624, P30CA015704, RG9216017
Status last verified
May 2021
First submitted
30 Aug 2016
Last updated
26 May 2021
Data monitoring committee
Yes

Publications

  • Pollack SM, Redman MW, Baker KK, Wagner MJ, Schroeder BA, Loggers ET, Trieselmann K, Copeland VC, Zhang S, Black G, McDonnell S, Gregory J, Johnson R, Moore R, Jones RL, Cranmer LD. Assessment of Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma: A Phase 1/2 Nonrandomized Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):1778-1782. doi: 10.1001/jamaoncol.2020.3689.

    PubMed 32910151

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Doxorubicin Hydrochloride, Laboratory Biomarker Analysis and Pembrolizumab in people with Sarcoma, run by Fred Hutchinson Cancer Center at 1 site 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 17 inclusion and 23 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 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 26 May 2021). 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?

Maximum Tolerated Dose (MTD) of Doxorubicin Hydrochloride Plus Pembrolizumab According to the National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) Version 4.0 (Phase I) (time frame: Up to 42 days (6 weeks)). The study lists 2 primary outcomes in all. 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 NCT02888665, 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 26 May 2021.

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