What is the mechanism of action of this treatment?

Nab-paclitaxel, a microtubule inhibitor, stabilizes microtubules and prevents their disassembly, inhibiting cell division and leading to cancer cell death. Gemcitabine, an antimetabolite, incorporates into DNA during replication, causing chain termination and apoptosis. These mechanisms are vital for Soft Tissue Sarcoma patients as they target rapidly dividing cancer cells, potentially reducing tumor growth and improving survival outcomes. Understanding these actions also aids in managing side effects and resistance, enhancing overall treatment efficacy.

What side effects are associated with this type of intervention?

Common treatments for Soft Tissue Sarcoma, including nab-paclitaxel and gemcitabine, are associated with several side effects. Nab-paclitaxel can cause neuropathy, fatigue, neutropenia, and diarrhea. Gemcitabine is known for causing myelosuppression, flu-like symptoms, and gastrointestinal disturbances. Other treatments like doxorubicin can lead to cardiotoxicity, alopecia, and mucositis, while ifosfamide is associated with neurotoxicity and hemorrhagic cystitis. Patients undergoing these treatments should be closely monitored for these adverse effects to manage them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for Soft Tissue Sarcoma (STS), including drugs with mechanisms similar to nab-paclitaxel and gemcitabine. Nab-paclitaxel, a microtubule inhibitor, and gemcitabine, an antimetabolite, are being studied for their efficacy in STS. Other FDA-approved treatments for STS include doxorubicin, an anthracycline antibiotic that intercalates DNA, and ifosfamide, an alkylating agent. These treatments have shown efficacy in various subtypes of STS, providing multiple options for patients depending on their specific diagnosis and treatment history.

What other types of research exist?

Promising novel alternatives to Nab-paclitaxel and Gemcitabine for Soft Tissue Sarcoma patients include: 1) Eribulin, which has shown improved overall survival in liposarcoma patients; 2) Trabectedin, particularly effective in myxoid/round cell liposarcoma; 3) Pazopanib, a multikinase angiogenesis inhibitor, effective in relapsed or refractory advanced STS; and 4) Nab-sirolimus, suggested for advanced unresectable or metastatic malignant neoplasm with perivascular epithelioid cell differentiation (PEComa).

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Anti-metabolites

nab-Paclitaxel + Gemcitabine for Sarcoma

Phase 2

Waitlist Available

Led By Javier E. Oesterheld, M.D.

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

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

Must have

Participants must be age ≥ 3 and ≤ 30 years, and have had a histologic diagnosis of osteosarcoma, Ewing sarcoma, or rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma either at diagnosis or relapse

Must have experienced relapse after front-line therapy, or have had documented disease progression during front-line therapy

Must not have

A history of allergic reactions attributed to docetaxel or paclitaxel

Uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 13 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if the combination of nab-paclitaxel and gemcitabine can stop tumors from growing in patients whose cancer has come back or did not respond to previous treatments. The study also checks if this combination is safe and tolerable. Nab-paclitaxel (Abraxane) is an albumin-bound paclitaxel that has shown clinical activity in advanced breast and lung cancer and has been tested in combination with gemcitabine for advanced pancreatic cancer, improving response rates and survival.

Who is the study for?

This trial is for young people aged 3 to 30 with certain types of sarcoma, including osteosarcoma and Ewing sarcoma, that have come back or didn't respond to initial treatments. They must have measurable disease, be in good physical condition with a Karnofsky score ≥60, and not pregnant. Participants should not have had prior treatment with the study drugs or recent chemotherapy and agree to use contraception.

What is being tested?

Researchers are testing if nab-Paclitaxel combined with Gemcitabine can stop tumor growth in patients whose sarcomas returned or resisted earlier treatments. The goal is also to see how long patients stay stable without their disease worsening after this treatment combination.

What are the potential side effects?

Possible side effects include allergic reactions similar to those from other taxane drugs (like docetaxel), nerve damage (neuropathy) up to a mild level at most, as well as typical chemotherapy-related issues like fatigue, nausea, low blood counts increasing infection risk.

Eligibility Criteria

Inclusion Criteria

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

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I am between 3 and 30 years old and have been diagnosed with a specific type of sarcoma.

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My cancer returned or got worse during my first treatment.

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My nerve damage symptoms are mild or not present.

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My cancer can be measured and tracked using specific criteria.

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I can care for myself but may need occasional help.

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My cancer has returned or is not responding to treatment, and there is no cure.

Exclusion Criteria

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

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I am allergic to docetaxel or paclitaxel.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I am not HIV-positive or not on antiretroviral therapy.

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I am not currently taking any cancer treatment medications.

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I am not taking medications that affect CYP2C8 or CYP3A4 enzymes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 13 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~13 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 13 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

Progression Free Survival (PFS)

Response Rate

Secondary study objectives

Occurrence of Study Treatment Related Adverse Events

Side effects data

From 2016 Phase 2 & 3 trial • 191 Patients • NCT01881230

55%

Fatigue

55%

Alopecia

43%

Nausea

42%

Diarrhoea

42%

Anaemia

40%

Neutropenia

30%

Vomiting

28%

Oedema peripheral

28%

Headache

25%

Decreased appetite

23%

Myalgia

23%

Peripheral sensory neuropathy

22%

Asthenia

22%

Arthralgia

22%

Constipation

20%

Pyrexia

20%

Cough

15%

Dysgeusia

13%

Rash

13%

Thrombocytopenia

13%

Hypokalaemia

13%

Hypertension

13%

Weight decreased

13%

Pain in extremity

13%

Insomnia

12%

Bone pain

12%

Dyspnoea

10%

Non-cardiac chest pain

10%

Upper respiratory tract infection

10%

Alanine aminotransferase increased

10%

Aspartate aminotransferase increased

10%

Dehydration

Pleural effusion

Abdominal pain upper

Stomatitis

Pruritus

Oropharyngeal pain

Pneumonia

Cellulitis

Neurotoxicity

Paraesthesia

Hot flush

Fall

Chills

Folliculitis

Leukopenia

Hyperglycaemia

Neuropathy peripheral

Depression

Erythema

Abdominal pain

Epistaxis

Dry mouth

Gastrooesophageal reflux disease

Generalised oedema

Influenza like illness

Pain

Sinusitis

Urinary tract infection

Spinal pain

Anxiety

Rash maculo-papular

Rash pruritic

Tachycardia

Back pain

Musculoskeletal chest pain

Dizziness

Rhinorrhoea

Dyspepsia

Drug hypersensitivity

Neck pain

Dry skin

Vision blurred

Bronchitis

Hypoaesthesia

Dyspnoea exertional

Lymphoedema

Haemorrhoidal haemorrhage

Haematemesis

Breast cellulitis

Cardiac failure

Palpitations

Device related infection

Metastases to meninges

Respiratory tract congestion

Lymphopenia

Lacrimation increased

Contusion

Overdose

Musculoskeletal pain

Atrial fibrillation

Sensory disturbance

Influenza

Hypomagnesaemia

Ascites

Endocarditis

Respiratory failure

Muscular weakness

Device related sepsis

Sepsis

Confusional state

Atelectasis

Pneumothorax

Pulmonary embolism

Deep vein thrombosis

Hepatic failure

Nodular regenerative hyperplasia

Febrile neutropenia

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Nab-Paclitaxel + Gemcitabine

Arm B: Nab-Paclitaxel + Carboplatin

Arm C: Gemcitabine + Carboplatin

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Combination TherapyExperimental Treatment2 Interventions

Participants will receive nab-Paclitaxel and Gemcitabine on days 1, 8, and 15 of each 28 day cycle, for up to 12 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

nab-Paclitaxel

2014

Completed Phase 3

~7680

Gemcitabine

2017

Completed Phase 3

~1920

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

Nab-paclitaxel, a microtubule inhibitor, stabilizes microtubules and prevents their disassembly, inhibiting cell division and leading to cancer cell death. Gemcitabine, an antimetabolite, incorporates into DNA during replication, causing chain termination and apoptosis. These mechanisms are vital for Soft Tissue Sarcoma patients as they target rapidly dividing cancer cells, potentially reducing tumor growth and improving survival outcomes. Understanding these actions also aids in managing side effects and resistance, enhancing overall treatment efficacy.

Fighting tubulin-targeting anticancer drug toxicity and resistance.Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.