Non-small-cell Lung Cancer With Somatic EGFR MutationsPhase 2MARBLENCT02488694
Maintaining ERBB Blockade in EGFR-mutated Lung Cancer
A Phase 2 study testing Afatinib and Pemetrexed in people with Non-small-cell Lung Cancer With Somatic EGFR Mutations, run by AIO-Studien-gGmbH at 1 site in Germany.
Trial summary
This study aims to compare the efficacy of afatinib maintenance with pemetrexed maintenance following induction therapy with platinum/ pemetrexed in patients with metastatic epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC) progressing after first-line treatment with afatinib with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small-cell Lung Cancer With Somatic EGFR Mutations
- What is being tested?
- Afatinib and Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteGermany
- Study dates
- Nov 2015to Dec 2017
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed diagnosis of non-small-cell lung cancer (NSCLC) with no curative therapeutic option. Patients with Stage IV (UICC 7th edition) disease or Stage IIIB disease not amenable to curative intent surgery or radiotherapy are enrolled. Patients with mixed histology are eligible if NSCLC is the predominant histology
- Documented somatic EGFR mutation as determined by medically accepted assay technology
- Patients with documented progression after response (CR/PR) or stable disease (SD) for at least 6 months of treatment with afatinib as first tyrosine kinase inhibitor (either given as first-line therapy or being switched to afatinib after up to 4 courses of platinum-based chemotherapy)
- Patients who have completed 3 or 4 cycles of cisplatin or carboplatin plus pemetrexed induction chemotherapy prior to randomization leading to documented response (CR/PR) or SD according to RECIST 1.1
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- Male or female patient with age ≥18 years
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- ECOG performance status ≤ 2
- Adequate organ and bone marrow function, defined as all of the following:
- Before the last cycle of induction chemotherapy or after hematopoietic recovery from the last cycle of induction chemotherapy:
- Absolute neutrophil count (ANC) ≥ 1,500 / mm3
- Platelet count ≥ 100,000 / mm3
- Creatinine clearance ≥ 45 ml / min (calculated according to Cockroft and Gault, or Tc99m-DPTA clearance or similar methodology). Patients with creatinine clearance of 45 to 79 ml/min should refrain from using NSAID at least 2 days before and 2 days after infusion of pemetrexed. Long-acting NSAID should be terminated 5 days before pemetrexed infusion.
- Total serum bilirubin ≤ 1.5 times upper limit of institutional normal (ULN)
- Serum aspartate amino transferase (AST) and serum alanine amino transferase (ALT) ≤ 3 times the upper limit of institutional normal (ULN) ( ≤ 5 times ULN if liver function abnormalities are due to underlying malignancy)
- Recovered from any previous therapy related toxicity to ≤ Grade 1 at study entry (except for stable sensory neuropathy ≤ Grade 2 and alopecia)
- Written informed consent
- Ability to comply with the protocol for the duration of the study, including hospital/office visits for treatment and scheduled follow-up visits and examinations
Who cannot join
- Systemic therapy for metastatic disease or relapse other than (a) first-line therapy with afatinib or (b) afatinib given as first EGFR-targeting agent following up to 4 courses of platinum-based chemotherapy with no disease progression between first-line chemotherapy and initiation of afatinib (prior adjuvant chemotherapy is allowed) and 3 to 4 cycles of induction chemotherapy with cisplatin or carboplatin and pemetrexed following afatinib failure
- Prior treatment with erlotinib, gefitinib or other investigational or approved EGFR-targeting small molecules or antibodies
- Known EGFR T790M mutation (analysis not mandatory)
- Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
- Extended radiotherapy within 4 weeks prior to randomization, except as follows:
- Palliative, limited local radiation to non-target lesions (e.g. isolated bone metastases) may be allowed up to 2 weeks prior to randomization, and
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- single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling
- Active brain metastases except for the followings:
- Asymptomatic brain metastases incidentally found during screening process which do not require local treatment in the opinion of the investigator.
- Asymptomatic brain metastases for which local treatment has been given: stable for at least 4 weeks of lower dose corticosteroids (e.g., dexamethasone up to 4 mg/d) and/or non-enzyme-inducing anti-convulsants treatment before study randomization.
- Brain metastases controlled after surgery and/or radiotherapy
- Meningeal carcinomatosis
- Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, non-invasive bladder cancer, ductal carcinoma in situ of the breast, or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. Definitively treated localized low/intermediate risk prostate cancer (Gleason score ≤ 7) is allowed when a rise in serum PSA level by ≥ 2 ng/mL above the nadir is excluded
- Known pre-existing interstitial lung disease
- Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug in the opinion of the investigator (e.g. Crohn's Disease, ulcerative colitis, chronic diarrhea, and malabsorption)
- Clinically relevant cardiovascular abnormalities as judged by the investigator such as uncontrolled hypertension, congestive heart failure ≥ NYHA grade III, unstable angina or myocardial infarction within the past 6 months, or poorly controlled cardiac arrhythmia in the opinion of investigator
- Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug, or renders the patient at high risk of treatment complications
- Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 weeks after treatment has ended
- Female patient pregnant or breast-feeding
- Known active infection with HBV, HCV or HIV
- Any contraindications for therapy with pemetrexed
- Known hypersensitivity to afatinib or the excipients of any of the trial drugs
- Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 60 days prior to treatment start
- Pleurocentesis or paracentesis should be considered in patients with clinically significant pleural effusions or ascites if clinically indicated. However, per SmPC of pemetrexed the presence of effusion is not an exclusion criteria
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open-label, Phase II Study of Maintaining Pan-ERBB Blockade Following Platinum-based Induction Chemotherapy in Patients With EGFR Mutated, Metastatic Non-small-cell Lung Cancer Progressing After Treatment With Afatinib as First EGFR-targeting Agent
This study aims to compare the efficacy of afatinib maintenance with pemetrexed maintenance following induction therapy with platinum/ pemetrexed in patients with metastatic epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC) progressing after first-line treatment with afatinib with respect to progression-free survival.
Read the detailed description
This is a randomized, open-label, phase II study of maintaining pan-ERBB blockade following platinum-based induction chemotherapy in patients with EGFR mutated, metastatic NSCLC progressing after first-line treatment with afatinib.
Patients who have progressed after first-line treatment with afatinib will be screened while receiving an induction phase which consists of at least three but not more than four cycles of cisplatin/carboplatin plus pemetrexed given in 21-day cycles. Patients who do not progress (i.e. complete or partial response, or stable disease - CR, PR or SD) after completion of three or four cycles induction chemotherapy will then be randomized (1:1 ratio) to receive maintenance therapy with either afatinib (40 mg/d, or last dose if reduced during first-line treatment) or pemetrexed (500 mg/m² every 21 days, or 375 mg/m² if dose was reduced during induction therapy) until disease progression, unacceptable toxicity or patient consent withdrawal.
- Being tested
- Afatinib, Pemetrexed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfatinibDrug
Also called GIOTRIF®
40 mg/d
PemetrexedDrug
Also called ALIMTA®
500 mg/m² i.v. on d1 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Afatinib | Experimental | 105 patients to be treated with afatinib Receives: Drug: Afatinib |
| Arm B: Pemetrexed | Active comparator | 105 patients to be treated with pemetrexed Receives: Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
The primary endpoint of this study is progression-free survival (RECIST 1.1).
Measured: 40 months
Secondary outcomes (4)
Overall survival
Efficacy measure
Measured: 40 months
Objective response rate
Objective response rate (ORR), clinical benefit rate (RECIST 1.1); Efficacy measure
Measured: 40 months
Quality of Life
Health-Related Quality of Life (HRQoL)
Measured: 40 month
Safety (intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.03)
Safety, toxicity (intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.03)
Measured: 40 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2015 (estimated)
- Study startNov 2015
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: unsufficient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small-cell Lung Cancer With Somatic EGFR MutationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- AIO-Studien-gGmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Martin Schuler, Prof. Dr., Principal investigator, Westdeutsches Tumorzentrum, Universitätsklinikum Essen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02488694
- Sponsor's protocol ID
- AIO-TRK-0114
- Acronym
- MARBLE
- Status last verified
- Jan 2018
- First submitted
- 30 Jun 2015
- Last updated
- 9 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Phase II Study of Maintaining Pan-ERBB Blockade Following Platinum-based Induction Chemotherapy in Patients With EGFR Mutated, Metastatic Non-small-cell Lung Cancer Progressing After Treatment With Afatinib as First EGFR-targeting Agent
- ClinicalTrials.gov ID
- NCT02488694
- Acronym / sponsor ID
- MARBLE / AIO-TRK-0114
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: unsufficient recruitment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- AIO-Studien-gGmbHUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim
- Study start
- Nov 2015
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 2 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to compare the efficacy of afatinib maintenance with pemetrexed maintenance following induction therapy with platinum/ pemetrexed in patients with metastatic epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC) progressing after first-line treatment with afatinib with respect to progression-free survival.
Detailed description
This is a randomized, open-label, phase II study of maintaining pan-ERBB blockade following platinum-based induction chemotherapy in patients with EGFR mutated, metastatic NSCLC progressing after first-line treatment with afatinib.
Patients who have progressed after first-line treatment with afatinib will be screened while receiving an induction phase which consists of at least three but not more than four cycles of cisplatin/carboplatin plus pemetrexed given in 21-day cycles. Patients who do not progress (i.e. complete or partial response, or stable disease - CR, PR or SD) after completion of three or four cycles induction chemotherapy will then be randomized (1:1 ratio) to receive maintenance therapy with either afatinib (40 mg/d, or last dose if reduced during first-line treatment) or pemetrexed (500 mg/m² every 21 days, or 375 mg/m² if dose was reduced during induction therapy) until disease progression, unacceptable toxicity or patient consent withdrawal.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Afatinib | Experimental | Drug: Afatinib105 patients to be treated with afatinib |
| Arm B: Pemetrexed | Active comparator | Drug: Pemetrexed105 patients to be treated with pemetrexed |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically or cytologically confirmed diagnosis of non-small-cell lung cancer (NSCLC) with no curative therapeutic option. Patients with Stage IV (UICC 7th edition) disease or Stage IIIB disease not amenable to curative intent surgery or radiotherapy are enrolled. Patients with mixed histology are eligible if NSCLC is the predominant histology
- Documented somatic EGFR mutation as determined by medically accepted assay technology
- Patients with documented progression after response (CR/PR) or stable disease (SD) for at least 6 months of treatment with afatinib as first tyrosine kinase inhibitor (either given as first-line therapy or being switched to afatinib after up to 4 courses of platinum-based chemotherapy)
- Patients who have completed 3 or 4 cycles of cisplatin or carboplatin plus pemetrexed induction chemotherapy prior to randomization leading to documented response (CR/PR) or SD according to RECIST 1.1
- At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Key exclusion criteria (24 listed)
- Systemic therapy for metastatic disease or relapse other than (a) first-line therapy with afatinib or (b) afatinib given as first EGFR-targeting agent following up to 4 courses of platinum-based chemotherapy with no disease progression between first-line chemotherapy and initiation of afatinib (prior adjuvant chemotherapy is allowed) and 3 to 4 cycles of induction chemotherapy with cisplatin or carboplatin and pemetrexed following afatinib failure
- Prior treatment with erlotinib, gefitinib or other investigational or approved EGFR-targeting small molecules or antibodies
- Known EGFR T790M mutation (analysis not mandatory)
- Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
- Extended radiotherapy within 4 weeks prior to randomization, except as follows:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfatinibAlso: GIOTRIF®40 mg/d | Drug | Arm A: Afatinib |
| PemetrexedAlso: ALIMTA®500 mg/m² i.v. on d1 of each 21-day cycle | Drug | Arm B: Pemetrexed |
Primary outcome
Progression-free survival
Time frame: 40 months
The primary endpoint of this study is progression-free survival (RECIST 1.1).
4 secondary outcomes
Overall survival
Time frame: 40 months
Objective response rate
Time frame: 40 months
Quality of Life
Time frame: 40 month
Safety (intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.03)
Time frame: 40 month
Results and safety
The study was stopped early (reason given: unsufficient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2018.
- Working Group for Medical Oncology (AIO) from the German Cancer Society (DKG)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Schuler, Prof. Dr. principal investigator
Westdeutsches Tumorzentrum, Universitätsklinikum Essen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afatinib and Pemetrexed in people with Non-small-cell Lung Cancer With Somatic EGFR Mutations, run by AIO-Studien-gGmbH at 1 site in Germany.
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 17 inclusion and 24 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 9 Jan 2018. 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 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 was stopped early (reason given: unsufficient recruitment). 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?
Progression-free survival (time frame: 40 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2018.