What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma (STS) include doxorubicin, pazopanib, and regorafenib, each with distinct side effect profiles. Doxorubicin is associated with cardiotoxicity, myelosuppression, alopecia, and mucosal inflammation. Pazopanib, a multikinase angiogenesis inhibitor, often causes hypertension, hypothyroidism, diarrhea, and less frequently, myelosuppression and alopecia. Regorafenib, another kinase inhibitor, commonly leads to asthenia, diarrhea, mucositis, acral erythema, anorexia, and arterial hypertension. Olaratumab, a monoclonal antibody targeting PDGFR-α, when combined with doxorubicin, has not shown a significant difference in overall survival compared to doxorubicin alone, but its side effects are generally consistent with those of monoclonal antibodies, including infusion reactions and potential immunogenicity.

What prior FDA approvals exist?

Olaratumab, a monoclonal antibody targeting PDGFR-α, was previously approved by the FDA for the treatment of advanced soft tissue sarcoma in combination with doxorubicin. However, it was later withdrawn from the market due to lack of improvement in overall survival. Other FDA-approved treatments for STS include doxorubicin-based regimens, which are commonly used either as single agents or in combination with other drugs like dacarbazine. Additionally, pazopanib, a tyrosine kinase inhibitor, is approved for patients with advanced STS who have received prior chemotherapy. These treatments highlight the ongoing efforts to find effective therapies for STS.

What other types of research exist?

Promising novel alternatives to Olaratumab for Soft Tissue Sarcoma patients include: <ol> <li>Pazopanib: A tyrosine kinase inhibitor that has shown activity in various STS subtypes, with a significant improvement in progression-free survival (PFS) in the PALETTE trial.</li> <li></li> </ol> Gemcitabine plus Docetaxel: This combination has demonstrated efficacy, particularly in leiomyosarcoma (LMS) and other histologies, with notable response rates. 3. Investigational agents such as Regorafenib, Cabozantinib, Sorafenib, and Lenvatinib combined with Etoposide and Ifosfamide, which have shown limited but promising activity in clinical studies.

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Anti-tumor antibiotic

Doxorubicin + Olaratumab for Soft Tissue Sarcoma (ANNOUNCE Trial)

Phase 3

Waitlist Available

Research Sponsored by Eli Lilly and Company

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed diagnosis of advanced unresectable or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy (excluding Kaposi's sarcoma and gastrointestinal stromal tumors)

Performance status 0-1 on the ECOG scale

Must not have

Active CNS or leptomeningeal metastasis at the time of randomization

Diagnosis of GIST or Kaposi sarcoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up randomization (cycle 1) through follow-up (up to 35.8 months)

Awards & highlights

Pivotal Trial

Summary

This trial is testing a new treatment that combines a standard cancer drug (doxorubicin) with a new drug (olaratumab) to see if it works better than the standard drug alone. It targets patients with advanced or metastatic soft tissue sarcoma, a severe form of cancer that has spread. The treatment aims to kill cancer cells directly with doxorubicin while also stopping their growth with olaratumab.

Who is the study for?

This trial is for adults with advanced or metastatic soft tissue sarcoma that can't be removed by surgery or treated with radiotherapy. Excluded are those with Kaposi's sarcoma, GIST, heart problems, QTcB interval issues on ECGs, pregnant/breastfeeding women, active infections including HIV/hepatitis, brain metastasis unless treated and stable for 60 days without steroids/anticonvulsants. Participants must not have had prior anthracycline therapy or olaratumab.

What is being tested?

The study tests the effectiveness of combining doxorubicin (a chemotherapy drug) with either olaratumab (an investigational drug) or a placebo in patients. The goal is to see if adding olaratumab improves outcomes compared to just doxorubicin alone.

What are the potential side effects?

Doxorubicin may cause side effects like hair loss, nausea/vomiting, mouth sores, and increased risk of infection due to low blood cell counts. Olaratumab could potentially cause infusion reactions such as fever/chills and allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My sarcoma cannot be removed by surgery or cured with radiation, and it's not Kaposi's sarcoma or a gastrointestinal stromal tumor.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have never been treated with anthracyclines.

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My tumor tissue is available for testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has spread to my brain or its coverings.

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I have been diagnosed with GIST or Kaposi sarcoma.

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I have had radiotherapy on specific parts of my body.

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I do not have any active infections, including HIV or hepatitis.

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I have not had recent heart issues like unstable angina, angioplasty, stenting, or a heart attack.

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I do not have severe heart problems like heart failure or irregular heartbeat.

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I have been treated with specific heart-related cancer drugs before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ randomization (cycle 1) through follow-up (up to 35.8 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~randomization (cycle 1) through follow-up (up to 35.8 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and randomization (cycle 1) through follow-up (up to 35.8 months) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS)

Overall Survival (OS) Leiomyosarcoma (LMS)

Secondary study objectives

Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)

Duration of Disease Control (DDC)

Duration of Overall Response (DoR)

+7 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Doxorubicin + OlaratumabExperimental Treatment2 Interventions

75 milligrams per meter squared (mg/m\^2) doxorubicin administered intravenously (IV) on day 1 of each 21-day cycle for 8 cycles plus 20 milligrams per kilogram (mg/kg) dose of olaratumab administered IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab administered IV on day 1 and day 8 of cycles 2-8. Beginning with cycle 9, 15 mg/kg olaratumab administered IV on day 1 and day 8 of each subsequent 21-day cycle until documented progressive disease (PD) or discontinuation for any other reason.

Group II: Doxorubicin + PlaceboPlacebo Group2 Interventions

75 mg/m\^2 doxorubicin administered IV on day 1 of each 21-day cycle for 8 cycles plus placebo (equivalent volume) administered IV on day 1 and day 8 for 8 cycles. Beginning with cycle 9, placebo (equivalent volume) administered on days 1 and 8 of each subsequent 21-day cycle until PD or discontinuation for any other reason.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaratumab

2010

Completed Phase 3

~1810

Doxorubicin

2012

Completed Phase 3

~8030

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Soft Tissue Sarcoma (STS) include chemotherapy agents like doxorubicin and targeted therapies such as olaratumab. Doxorubicin works by intercalating DNA strands, thereby inhibiting the replication of cancer cells. Olaratumab, a monoclonal antibody, targets the platelet-derived growth factor receptor alpha (PDGFR-α), blocking its signaling pathways which are crucial for tumor growth and survival. This targeted approach is significant for STS patients as it offers a more precise attack on cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Regorafenib for the Treatment of Sarcoma.Olaratumab: a platelet-derived growth factor receptor-α-blocking antibody for the treatment of soft tissue sarcoma.Trabectedin and olaparib in patients with advanced and non-resectable bone and soft-tissue sarcomas (TOMAS): an open-label, phase 1b study from the Italian Sarcoma Group.