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Carcinoma, Non-small-cell LungPhase 3IDANCT02004184

Pemetrexed in Advanced Non-Small-Cell Lung Cancer: at Progression vs Maintenance Therapy After Induction Chemotherapy

A Phase 3 study testing maintenance pemetrexed and pemetrexed at progression in people with Carcinoma, Non-small-cell Lung, run by Norwegian University of Science and Technology at 1 site in Norway.

Terminated

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

Official record
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Trial summary

Non-small-cell lung cancer (NSCLC) accounts for a majority (approximately 85%) of lung cancer cases. Patients with localized disease can be cured through surgery, but only 20 % are operable.For the majority of patients with advanced disease, palliative cytotoxic chemotherapy remains the recommended therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-small-cell Lung
What is being tested?
maintenance pemetrexed and pemetrexed at progression
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
230 participants
Where
1 siteNorway
Study dates
Dec 2013to Mar 2018
Phase
Phase 3
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

  • Measureable disease according to the RECIST 1.1
  • Previous radiotherapy is acceptable provided there are measurable, previously not irradiated lesions present
  • Histologically or cytologically confirmed non-squamous non-small cell lung cancer
  • Stage IIIB ineligible for curative therapy or stage IV disease
  • ECOG Performance 0-2
  • Adequate organ function defined as:
Show all 14Show fewer
  • Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy.
  • Total serum bilirubin ≤ 1.5 x ULN
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Creatinine clearance > 45 ml/min
  • Able to discontinue NSAIDs and ASA if reduced renal function
  • All fertile patients should use safe contraception
  • Written informed consent

Who cannot join

  • prior systemic therapy for advanced non-small-cell lung cancer (including EGFR-TKI). Previous chemotherapy (e.g. adjuvant after surgery or for other cancer) is allowed if ≥ 3 months since the last course was administered.
  • activating EGFR-mutation or ALK-translocation detected
  • serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) that in the opinion of the investigator would compromise the patient's ability to complete the study or interfere with the evaluation of the efficacy and safety of the study treatment
  • conditions - medical, social, psychological - which could prevent adequate information and follow-up
  • clinically active cancer other than NSCLC
  • known hypersensitivity or contraindications for the study drugs (vinorelbine, carboplatin, pemetrexed, B12, folate)
  • pregnant or lactating women

Trial locations and contacts

1 site in 1 country.

Norway1 site

  • St Olavs Hospital

    Trondheim

Other trials in Norway

About this study

Official title: Maintenance Pemetrexed Therapy After Induction Chemotherapy Versus Pemetrexed at Progression in Advanced Non-Small-Cell Lung Cancer: A Randomized Phase III Study

Non-small-cell lung cancer (NSCLC) accounts for a majority (approximately 85%) of lung cancer cases. Patients with localized disease can be cured through surgery, but only 20 % are operable.For the majority of patients with advanced disease, palliative cytotoxic chemotherapy remains the recommended therapy. Chemotherapy prolongs survival and improves quality of life.

The recommended first-line therapy is 4-6 courses of a platinum in combination with a third generation compound (e.g. gemcitabine, vinorelbine, docetaxel, pemetrexed, paclitaxel). After first-line therapy, it has been recommended to observe the patients and offer second-line chemotherapy at disease progression.

Read more

Regimens for second-line therapy include docetaxel or pemetrexed monotherapy. Pemetrexed is less toxic and superior to gemcitabine in non-squamous NSCLC, whereas docetaxel is the recommended second-line therapy in squamous cell carcinoma.

The results of the studies of maintenance pemetrexed therapy are encouraging; the observed survival benefit is clinically relevant and relatively large considering the poor survival in patients with advanced NSCLC. Furthermore, pemetrexed appears to be well tolerated. There are, however, several limitations to the studies that have been conducted: Relatively few elderly patients and no PS 2 patients were enrolled - and not all patients on the control-arms received pemetrexed at progression.

The overall aim of this study is to investigate whether immediate maintenance pemetrexed therapy prolongs survival compared to observation and pemetrexed therapy at progression in patients with advanced NSCLC. Furthermore, it will be explored whether patients with 'performance status' 2 and elderly ≥ 70 years tolerate and benefit from maintenance therapy; and what characteristics and blood biomarkers are associated with sensitivity and tolerability of such therapy.

Read the detailed description

In previous studies without maintenance therapy, median overall survival (OS) for performance status (PS) 0-1 patients has been approximately 9 months, corresponding to 6 months from randomization in this study. We consider an improvement in overall survival of two months to be the minimum difference that will lead to routine use of maintenance pemetrexed in Norway. To demonstrate an improvement in median overall survival from 6 to 8 months with an α =0.05 and β =0.20, 198 evaluable patients are required on each arm. We expect a drop-out rate of maximum 10 %, and therefore intend to randomize a total of 436 patients (PS 0-1) - of which we expect 150 to be 70 years or older.

Sample size is calculated on PS 0-1 patients only. In addition, PS 2 patients will be randomized until the required number of PS 0-1 patients have been accrued. We estimate that a total of 100 PS 2 patients will be enrolled - sufficient for hypothesis-generating analyses of the benefit of maintenance therapy in elderly and PS 2 patients.

Based on experience from our previous studies we estimate that approximately 30% of patients will not complete or progress during induction chemotherapy; or be ineligible due deterioration of PS. Consequently, we need to include approximately 765 patients.

Being tested
maintenance pemetrexed, pemetrexed at progression
Keywords
Pemetrexed, drug therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • maintenance pemetrexedDrug

    Also called Alimta

    500 mg/m2 Body Surface Area is administered intravenously every 3 weeks

  • pemetrexed at progressionDrug

    Also called Alimta

    500 mg/m2 Body Surface Area is administered intravenously every 3 weeks

Study groups in NCT02004184
Study groupRoleWhat they receive
maintenance pemetrexedExperimentalmaintenance pemetrexed immediately after induction chemotherapy
Receives: Drug: maintenance pemetrexed
pemetrexed at progressionActive comparatorobservation and pemetrexed therapy at disease progression
Receives: Drug: pemetrexed at progression

What is being measured

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

  1. overall survival

    All patients will be followed until death of any reason - assessed up to 24 months after inclusion in the study.

    Measured: 2 years

Secondary outcomes (3)

  1. progression free survival

    From date of inclusion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

    Measured: 2 years

  2. Toxicity

    All patients will be followed for 2 years (or until 1 month after the end of study therapy if study therapy is discontinued before 2 years after study inclusion).

    Measured: 2 years

  3. Health related quality of life

    All patients will be followed until discontinuation of study therapy - up to 24 months after inclusion in the study.

    Measured: 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 posted9 Dec 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionMar 2018
  4. Study completionMar 2018

Why it stopped: Poor enrollment due to the introduction of immunotherapy

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
230 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02004184
Sponsor's protocol ID
2013/645
Other IDs
2013-001237-41
Acronym
IDA
Status last verified
Jun 2020
First submitted
19 Nov 2013
Last updated
23 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Halvorsen TO, Stokke K, Killingberg KT, Raj SX, Sorhaug S, Brustugun OT, Flotten O, Helbekkmo N, Hornslien K, Madebo T, Fluge S, Gronberg BH. Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC. Acta Oncol. 2020 Sep;59(9):1051-1057. doi: 10.1080/0284186X.2020.1778179. Epub 2020 Jun 16.

    PubMed 32543258

  • Stokke K, Sandvei MS, Gronberg BH, Slaaen M, Killingberg KT, Halvorsen TO. Prognostic Value of Post First-Line Chemotherapy Glasgow Prognostic Score in Advanced Non-Small Cell Lung Cancer. Clin Med Insights Oncol. 2022 Mar 22;16:11795549221086578. doi: 10.1177/11795549221086578. eCollection 2022.

    PubMed 35342321

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing maintenance pemetrexed and pemetrexed at progression in people with Carcinoma, Non-small-cell Lung, run by Norwegian University of Science and Technology at 1 site in Norway.

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 14 inclusion and 7 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 23 Jun 2020. 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 Norway. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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: Poor enrollment due to the introduction of immunotherapy). 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?

overall survival (time frame: 2 years). 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 NCT02004184, which also lists 2 linked publications.

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 23 Jun 2020.

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