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

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ClinicalTrials.gov Identifier: NCT02004184
Recruitment Status : Terminated (Poor enrollment due to the introduction of immunotherapy)
First Posted : December 9, 2013
Last Update Posted : May 7, 2018
Sponsor:
Collaborator:
St. Olavs Hospital
Information provided by (Responsible Party):
Norwegian University of Science and Technology

Brief 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. 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.

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.


Condition or disease Intervention/treatment Phase
Carcinoma, Non-small-cell Lung Drug: maintenance pemetrexed Drug: pemetrexed at progression Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Maintenance Pemetrexed Therapy After Induction Chemotherapy Versus Pemetrexed at Progression in Advanced Non-Small-Cell Lung Cancer: A Randomized Phase III Study
Actual Study Start Date : December 2013
Actual Primary Completion Date : March 2018
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: maintenance pemetrexed
maintenance pemetrexed immediately after induction chemotherapy
Drug: maintenance pemetrexed
500 mg/m2 Body Surface Area is administered intravenously every 3 weeks
Other Name: Alimta

Active Comparator: pemetrexed at progression
observation and pemetrexed therapy at disease progression
Drug: pemetrexed at progression
500 mg/m2 Body Surface Area is administered intravenously every 3 weeks
Other Name: Alimta




Primary Outcome Measures :
  1. overall survival [ Time Frame: 2 years ]
    All patients will be followed until death of any reason - assessed up to 24 months after inclusion in the study.


Secondary Outcome Measures :
  1. progression free survival [ Time Frame: 2 years ]
    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.

  2. Toxicity [ Time Frame: 2 years ]
    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).

  3. Health related quality of life [ Time Frame: 2 years ]
    All patients will be followed until discontinuation of study therapy - up to 24 months after inclusion in the study.


Other Outcome Measures:
  1. Overall survival in elderly and PS 2 patients [ Time Frame: 2 years ]
    All patients will be followed until death of any reason - assessed up to 24 months after inclusion in the study.

  2. Associations between clinical characteristics and blood biomarkers - and outcomes of therapy [ Time Frame: 2 years ]
    All patients will be followed until death of any reason - assessed up to 24 months after inclusion in the study.

  3. Toxicity in elderly and PS 2 patients [ Time Frame: 2 years ]
    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).

  4. Health related quality of life in elderly and PS 2 patients [ Time Frame: 2 years ]
    All patients will be followed until discontinuation of study therapy - up to 24 months after inclusion in the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    1. 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.
    2. Total serum bilirubin ≤ 1.5 x ULN
    3. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    4. Platelets ≥ 100 x 109/L
    5. 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02004184


Locations
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Norway
St Olavs Hospital
Trondheim, Norway
Sponsors and Collaborators
Norwegian University of Science and Technology
St. Olavs Hospital
Investigators
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Principal Investigator: Bjørn H Grønberg, MD PhD Norwegian University of Science and Technology

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Responsible Party: Norwegian University of Science and Technology
ClinicalTrials.gov Identifier: NCT02004184     History of Changes
Other Study ID Numbers: 2013/645
2013-001237-41 ( EudraCT Number )
First Posted: December 9, 2013    Key Record Dates
Last Update Posted: May 7, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Norwegian University of Science and Technology:
Pemetrexed
drug therapy

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors