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Malignant MesotheliomaPhase 2NCT00334594

Pemetrexed Disodium and Cisplatin Followed by Surgery With or Without Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

A Phase 2 study testing Cisplatin, Pemetrexed and Therapeutic conventional surgery in people with Malignant Mesothelioma, run by Swiss Cancer Institute at 13 sites in 2 countries.

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

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 to 69 years
Conditions the study is for
Malignant Mesothelioma
What is being tested?
Cisplatin, Pemetrexed and Therapeutic conventional surgery
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
13 sitesin 2 countries
Study dates
14 Nov 2005to 23 Jan 2018
Phase
Phase 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 to 69 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed malignant pleural mesothelioma
  • T1-3, N0-2, M0 disease according to International Mesothelioma Interest Group staging system
  • No obvious invasion of mediastinal structures by CT scan (e.g., heart, aorta, spine, esophagus)
  • No obvious widespread chest wall invasion
  • Resectable chest wall lesions allowed

PATIENT CHARACTERISTICS:

  • WHO performance score 0-1
  • Fit for neoadjuvant therapy, surgery, and postoperative radiotherapy
  • Creatinine clearance > 60 mL/min
  • Hemoglobin ≥ 10.0 g/dL
  • WBC ≥ 3,500/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 12 months after completion of study treatment
  • FEV_1 ≥ 40% of predicted based on spirometry and lung perfusion scan, if necessary
  • No serious underlying medical condition that would preclude study requirements (e.g., active autoimmune disease or uncontrolled diabetes)
  • No known hypersensitivity against pemetrexed disodium, cisplatin, or other platinum-containing substances or any other components used for the preparation of the drugs
  • No restricted power of hearing (especially in the upper frequency range)
  • No acute infections

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy
  • No treatment on another clinical trial within the past 30 days
  • No prior pleurectomy or lung resection
  • No prior radiotherapy of the lower neck, thorax, or upper abdomen
  • No aspirin, cyclooxygenase-2 inhibitors, or nonsteroidal anti-inflammatory agents for 5 days prior to, during, and for 2 days after pemetrexed disodium administration
  • No other concurrent experimental drugs or anticancer therapy
  • No concurrent drugs that would contraindicate study drugs
  • No concurrent vaccination against yellow fever

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

Switzerland12 sites
  • Kantonsspital Aarau

    Aarau, CH-5001

  • Kantonsspital Baden

    Baden, CH-5404

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Spital Tiefenau

    Bern, 3004

  • Inselspital Bern

    Bern, CH-3010

  • Kantonsspital Bruderholz

    Bruderholz, CH-4101

  • Kantonsspital Graubuenden

    Chur, CH-7000

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, CH-1011

  • Kantonsspital Olten

    Olten, CH-4600

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • SpitalSTS AG Simmental-Thun-Saanenland

    Thun, 3600

  • UniversitaetsSpital Zuerich

    Zurich, CH-8091

Other trials in Switzerland

Germany1 site
  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, D-79106

Other trials in Germany

About this study

Official title: Neoadjuvant Chemotherapy and Extrapleural Pneumonectomy of Malignant Pleural Mesothelioma (MPM) With or Without Hemithoracic Radiotherapy. A Randomized Multicenter Phase II Trial

RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium together with cisplatin followed by surgery with or without radiation therapy works in treating patients with malignant pleural mesothelioma.

Read the detailed description

OBJECTIVES:

Primary

  • Evaluate the short-term outcomes and feasibility of neoadjuvant therapy with pemetrexed disodium and cisplatin followed by extrapleural pneumonectomy in patients with malignant pleural mesothelioma.
  • Evaluate the long-term outcomes and feasibility of postoperative hemithoracic radiotherapy in patients with R0 or R1 resection.

Secondary

  • Determine the quality of life of these patients.
  • Identify predictive and prognostic markers in these patients.
  • Determine relapse-free or progression-free survival and overall survival of these patients.
  • Collect tissue and blood from these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, histology (sarcomatous or other vs epithelial or mixed histology), nodal status (N0-1 vs N2), and extent of disease (T1-2 vs T3).

  • Part 1 (neoadjuvant therapy and surgery): Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 8 weeks after completion of neoadjuvant therapy, patients without progressive disease undergo extrapleural pneumonectomy.
  • Part 2 : Patients achieving R0 or R1 resection proceed to part 2 of study treatment and are randomized to 1 of 2 treatment arms. Patients with R2 resection, disease progression, or symptomatic deterioration after treatment in part 1 are taken off study.
  • Arm I (no postoperative radiotherapy): Patients do not undergo radiotherapy. Quality of life is assessed at baseline and at 6, 10, 16, and 22 weeks after randomization.
  • Arm II (postoperative radiotherapy): Beginning within 10 weeks after surgery, patients undergo radiotherapy to the hemithoracic region 5 days a week for approximately 5 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at 4, 8, 14, and 20 weeks after initiation of radiotherapy.

Patients undergo blood and tissue collection at registration and surgery for laboratory and biomarker analysis.

After completion of study treatment, patients are followed periodically for up to 5 years after surgery.

PROJECTED ACCRUAL: A total of 155 patients will be accrued for this study.

Keywords
epithelial mesothelioma, sarcomatous mesothelioma, stage IA malignant mesothelioma, stage IB malignant mesothelioma, stage II malignant mesothelioma, stage III malignant mesothelioma
Medical subject headings
Mesothelioma, Malignant, Solitary Fibrous Tumor, Pleural

What participants receive

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

  • CisplatinDrug

    Cisplatin 75 mg/m2 i.v. over approximately 2 hours on day 1 every 21 days

  • PemetrexedDrug

    Pemetrexed 500 mg/m2 i.v. over approximately 10 minutes on day 1 every 21 days

  • Therapeutic conventional surgeryProcedure or surgery

    Extrapleural pneumonectomy

  • RadiotherapyRadiation

    CTV1 will receive 45 or 46 Gy. CTV2 will be treated up to a total dose of 55,9 to 56,2 Gy.

Study groups in NCT00334594
Study groupRoleWhat they receive
No radiotherapyActive comparatorNot described
Receives: Drug: Cisplatin; Drug: Pemetrexed; Procedure: Therapeutic conventional surgery
RadiotherapyExperimentalNot described
Receives: Drug: Cisplatin; Drug: Pemetrexed; Procedure: Therapeutic conventional surgery; Radiation: Radiotherapy

What is being measured

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

  1. Complete macroscopic resection (part 1)

    Measured: After surgery (15 weeks after trial registration)

  2. Loco-regional relapse-free survival (part 2)

    Measured: From surgery until the first occurrence of loco-regional relapse

Secondary outcomes (12)
  1. Response to neoadjuvant therapy (part 1)

    Measured: Every 6 months in the follow-up until death for a maximum of 5 years

  2. Adverse drug reaction to neoadjuvant therapy (part 1)

    Measured: According to CTCAE

  3. Operability (part 1)

    Measured: Proportion of patients remaining operable after completing chemotherapy (9 weeks after trial registration)

  4. Surgical complications (part 1)

    Measured: Within 3 month after surgery

  5. Reasons for non-randomization (part 1)

    Measured: Reasons for non-randomization include macroscopic incomplete resection, patients' refusal or patient can not be subjected to RT within 10 weeks after surgery.

  6. Relapse-free or progression-free survival (part 1)

    Measured: From registration until progression/relapse (loco-regional or distant) or death

  7. Adverse reaction to postoperative radiotherapy (part 2)

    Measured: According to CTCAE

  8. Late toxicity (part 2)

    Measured: Late toxicities occurring later than 6 weeks after the last RT fraction

  9. Feasibility of postoperative radiotherapy (part 2)

    Measured: Proportion of patients receiving at least 90% of planned RT dose

  10. Relapse-free survival (part 2)

    Measured: From registration until progression/relapse (loco-regional or distant) or death

  11. Psychological distress (quality of life) (part 2)

    Measured: Until 22 weeks after treatment termination

  12. Overall survival

    Measured: From registration until death for all registered patients, and from randomization to death for all randomized patients.

Timeline

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

  1. First posted8 Jun 2006 (estimated)
  2. Study start14 Nov 2005
  3. Primary completion26 Mar 2014
  4. Study completion23 Jan 2018

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00334594
Sponsor's protocol ID
SAKK 17/04
Other IDs
SWS-SAKK-17/04, EU-20615, 2006-000445-19, LILLY-SAKK-17/04, CDR0000481153
Status last verified
May 2019
First submitted
7 Jun 2006
Last updated
15 May 2019
Results posted
No
Data monitoring committee
No

Publications

  • Stahel RA, Riesterer O, Xyrafas A, Opitz I, Beyeler M, Ochsenbein A, Fruh M, Cathomas R, Nackaerts K, Peters S, Mamot C, Zippelius A, Mordasini C, Caspar CB, Eckhardt K, Schmid RA, Aebersold DM, Gautschi O, Nagel W, Topfer M, Krayenbuehl J, Ribi K, Ciernik IF, Weder W. Neoadjuvant chemotherapy and extrapleural pneumonectomy of malignant pleural mesothelioma with or without hemithoracic radiotherapy (SAKK 17/04): a randomised, international, multicentre phase 2 trial. Lancet Oncol. 2015 Dec;16(16):1651-8. doi: 10.1016/S1470-2045(15)00208-9. Epub 2015 Nov 2.

    PubMed 26538423

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, Pemetrexed and Therapeutic conventional surgery in people with Malignant Mesothelioma, run by Swiss Cancer Institute at 13 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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 15 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Switzerland, Germany. 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 phase mean?

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Complete macroscopic resection (part 1) (time frame: After surgery (15 weeks after trial registration)). 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 NCT00334594, 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 15 May 2019.

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