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Soft Tissue SarcomaPhase 1/2NCT03524898

NAPAGE: NAb-PAclitaxel and GEmcitabine in Advanced Soft Tissue Sarcoma

A Phase 1/2 study testing Nab-Paclitaxel and gemcitabine in people with Soft Tissue Sarcoma, run by Swiss Cancer Institute at 8 sites in Switzerland.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

A clinical trial with biweekly regimen of gemcitabine and nab-paclitaxel for Soft tissue sarcomas (STSs). A Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Nab-Paclitaxel and gemcitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
8 sitesSwitzerland
Study dates
2 Oct 2018to 15 Feb 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Histologically confirmed minimum grade 2, locally advanced or metastatic STS refractory to chemotherapy and not suitable for local treatment.
  • Minimum one line and maximum 2 lines of previous chemotherapy for advanced/metastatic STS
  • Measurable disease according to RECIST v1.1
  • Age ≥ 18 years
  • WHO performance status 0-2
  • Adequate hematological, hepatic and renal function
Show all 9Show fewer
  • Negative pregnancy test
  • Effective method of birth control
  • Peripheral neuropathy at enrolment must be ≤ grade 1

Who cannot join

  • Uncontrolled CNS metastases
  • Previous or concomitant malignancy diagnosed within 3 years
  • More than 2 lines of previous systemic treatment for STS
  • Previous sarcoma treatment with gemcitabine and/or nab-paclitaxel or other taxanes
  • Radiotherapy within 4 weeks prior to registration
  • Concurrent or recent treatment with any other experimental drug
Show all 13Show fewer
  • Concomitant use of other anti-cancer drugs
  • Severe or uncontrolled cardiovascular disease
  • History of cerebrovascular accident or intracranial hemorrhage within 2 months prior to registration
  • Evidence of active, noninfectious pneumonitis or history of interstitial lung disease
  • Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection
  • Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information
  • Known hypersensitivity to the trial drug(s)

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Switzerland8 sites

  • Universitaetsspital Basel

    Basel, CH-4031

  • Istituto Oncologico della Svizzera Italiana

    Bellinzona, 6500

  • Inselspital, Bern

    Bern, CH-3010

  • Kantonsspital Graubünden

    Chur, 7000

  • Hopital Cantonal Universitaire de Geneve

    Geneva, CH-1211

  • CHUV - Swiss Cancer Center Lausanne

    Lausanne, 1011

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • UniversitätsSpital Zürich

    Zurich, 8091

Other trials in Switzerland

About this study

Official title: NAPAGE: NAb-PAclitaxel and GEmcitabine in Advanced Soft Tissue Sarcoma. A Multicenter Open-label Single Arm Phase Ib/IIa Trial

A clinical trial with biweekly regimen of gemcitabine and nab-paclitaxel for Soft tissue sarcomas (STSs).

A Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients.

Read more

Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel particles (Celgene, Summit, NJ) which was designed to eliminate the toxicities associated with Cremophor®-EL. Nab-paclitaxel at equal dose of paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intra-tumor paclitaxel concentration in preclinical models of solid tumor xenografts promising an advantageous pharmacokinetic profile In sarcoma, nab-paclitaxel demonstrated preclinical anti-tumor activity in rhabdomyosarcoma xenograft model. Local relapsed tumors following paclitaxel treatment proved to be paclitaxel-resistant but remained responsive to nab-paclitaxel.

These findings provide the rationale for further evaluation of nab-paclitaxel in combination with gemcitabine for soft tissue sarcoma treatment.

Read the detailed description

Soft tissue sarcomas (STSs) account for 1% of all human cancers and consist of at least 50 different histological subtypes which have different clinical behavior and response to chemotherapy. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis with a median OS between 12 and 15 months.

Palliative chemotherapy is the mainstay of treatment in the metastatic setting, although in a small subset with limited metastases local treatment may be curative. First-line treatment for advanced soft-tissue sarcoma includes doxorubicin hydrochloride, alone or in combination with other chemotherapy agents (e.g., ifosfamide), or olaratumab. Beyond first line several agents have shown activity, including gemcitabine/docetaxel, trabectedin and pazopanib, though no standard regimen has been established.

Promising antitumor activity in patients with metastatic STS has been reported with gemcitabine alone or in combination with taxanes including docetaxel and paclitaxel in pre-treated patients.

Nab-paclitaxel is a 130-nm albumin-bound formulation of paclitaxel particles (Abraxane®, Celgene, Summit, NJ) which was designed to eliminate the toxicities associated with Cremophor EL®. Nab-paclitaxel at equal dose of paclitaxel showed increased antitumor activity, enhanced endothelial cell transport and 33% higher intra-tumor paclitaxel concentration in preclinical models of solid tumor xenografts promising an advantageous pharmacokinetic profile In sarcoma, nab-paclitaxel demonstrated preclinical antitumor activity in rhabdomyosarcoma xenograft model. Local relapsed tumors following paclitaxel treatment proved to be paclitaxel-resistant but remained responsive to nab-paclitaxel.

These findings provide the rationale for further evaluation of nab-paclitaxel in combination with gemcitabine for soft tissue sarcoma treatment.

Phase Ib objective:

  • To assess the safety and feasibility of combining nab-paclitaxel and gemcitabine

Phase II objective:

  • To determine whether or not gemcitabine/nab-paclitaxel regimen exhibits antitumor activity that is worth testing further in STS.
Keywords
Nab-Paclitaxel, Gemcitabine, Advanced soft tissue sarcoma, Cancer, Sarcoma, Abraxane®
Medical subject headings
Sarcoma, Neoplasms

What participants receive

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

Study groups in NCT03524898
Study groupRoleWhat they receive
nab-paclitaxel and gemcitabineExperimentalTreatment consists of the combination treatment of nab-paclitaxel and gemcitabine, which is given every 2 weeks during 28-day cycle intervals until disease progression.
Receives: Drug: Nab-Paclitaxel; Drug: gemcitabine

What is being measured

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

  1. Phase I: Dose-limiting toxicity (DLT)

    DLT is defined as any of the following adverse events (AEs) occurring during the first cycle of treatment and regarded by the investigators and/or the Sponsor to be related to nab-paclitaxel and/or gemcitabine (AEs not related to the IMPs are not regarded as DLT)

    Measured: during the first cycle of treatment (28 days)

  2. Phase II: Progression-free rate (PFR)

    PFR at 12 weeks after registration determined by the percentage of progression-free patients at 12 weeks. Progression is defined as one of the following events (whichever occurs first):

    • Progressive disease (PD) assessed according to the RECIST v1.1 before week 13 (allowed is a 1 week delay in the tumor assessment at week 12).
    • Death due to any cause up to week 12.
    • Start of second line treatment before week 12.
    • No tumor assessment after week 11 without subsequent treatment which shows stabilization or response.

    Measured: at 12 weeks after registration

Secondary outcomes (9)

  1. Phase I: PFR 12 weeks

    Measured: at 12 weeks after registration

  2. Phase I: Best response assessed according to RECIST v1.1

    Measured: assessed for up to 5 years after patient registration

  3. Phase I: Adverse events (AEs), assessed according to NCI CTCAE v4.03

    Measured: assessed for up to 5 years after patient registration

  4. Phase II: Progression-free survival (PFS)

    PFS defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first.

    Patients without an event at the time of analysis and patients starting a new anticancer therapy in the absence of an event will be censored at the date of the last tumor assessment before the start of the new therapy, if any.

    Measured: assessed for up to 5 years after patient registration

  5. Phase II: Overall Survival (OS)

    OS defined as the time from registration until death from any cause. Patients without an event at the time of analysis will be censored at the date they were last known to be alive.

    Measured: assessed for up to 5 years after patient registration

  6. Phase II: Best response assessed according to RECIST v1.1

    Measured: assessed for up to 5 years after patient registration

  7. Phase II: AEs, assessed according to NCI CTCAE v4.03

    Measured: from registration until 28 days after administration of the last dose of trial treatment

  8. Phase II: Symptom-related quality of life assessed by questionnaires

    Symptom-related quality of life will be assessed with the M.D. Anderson Symptom Inventory (MDASI), which measures the severity of 13 cancer-related symptoms and their impact on six dimensions of daily life at their worst in the last 24 hours on a 0-10 numerical rating scale, with 0 being "not present" and 10 being "as bad as you can imagine."

    Measured: assessed for up to 5 years after patient registration

  9. Phase II: Nab-paclitaxel related sensory neuropathy assessed by questionnaires

    To address an important side-effect of nab-paclitaxel, sensory neuropathy will be assessed by the 4-item subscale of the FACT/GOG-Ntx (Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity), which measures the severity of sensory neuropathy in the last 7 days on a 0-4 numerical rating scale, with 0 being "not at all" and 4 being "very much."

    Measured: assessed for up to 5 years after patient registration

Timeline

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

  1. First posted15 May 2018
  2. Study start2 Oct 2018
  3. Primary completion15 Feb 2022
  4. Study completion15 Feb 2022

Why it stopped: As Last patient last visit (LPLV) took place on 15/02/2022, the trial was ended prematurely on this date in accordance with SAKK/CI.

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
Model description
This is a single-arm phase Ib/IIa multi-center study in patients with locally advanced or metastatic soft tissue sarcoma who have received first line or second line chemotherapy with no response or with evidence of disease progression.
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03524898
Sponsor's protocol ID
SAKK 57/16 - NAPAGE
Status last verified
Sep 2022
First submitted
24 Apr 2018
Last updated
28 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nab-Paclitaxel and gemcitabine in people with Soft Tissue Sarcoma, run by Swiss Cancer Institute at 8 sites in Switzerland.

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 9 inclusion and 13 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: stopped early, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Switzerland. 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?

The study was stopped early (reason given: As Last patient last visit (LPLV) took place on 15/02/2022, the trial was ended prematurely on this date in accordance with SAKK/CI.). Results are not available in the source record.

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?

Phase I: Dose-limiting toxicity (DLT) (time frame: during the first cycle of treatment (28 days)). 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 NCT03524898.

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 28 Sep 2022.

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