Carcinoma, Non-Small-Cell LungPhase 1iTRAPNCT03498222
Study in Patients With Tumours Requiring Arginine to Assess ADI-PEG 20 With Atezolizumab, Pemetrexed and Carboplatin
A Phase 1 study testing Atezolizumab, Pemetrexed and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Queen Mary University of London.
Trial summary
iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung carcinoma (NSCLC) - stage IIIB/IV. 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?
- Atezolizumab, Pemetrexed and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jun 2018to 31 Dec 2021
- Phase
- Phase 1
- 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
- Willing and able to provide written informed consent prior to study entry.
- Age ≥ 18 years.
- Histologically proven advanced non-squamous NSCLC (stage IIIB/IV) not treated with chemotherapy or immunotherapy - immunotherapy for uveal melanoma and prior (neo)adjuvant chemotherapy is permitted. Patients with EGFR mutant or ALK positive NSCLC must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial.
- ASS1 deficiency defined as ≤50% ASS expression on tissue specimen by immunohistochemistry (IHC) (cytospin samples are acceptable) - assessed centrally. For patients previously treated with (neo)adjuvant chemotherapy, this specimen may have been obtained before that chemotherapy.
- Measurable disease as assessed by RECIST 1.1 i.e. at least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements OR lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable disease as defined above; NOTE: patients with sclerotic / osteoblastic bone lesions only in the absence of measurable disease are not eligible)
- ECOG performance status of 0 - 1
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- Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating study treatment. Surgery for placement of vascular access devices is acceptable.
- Female patients of childbearing potential and their partners (if male) and male patients with female partners of childbearing potential and their partners must agree to use a highly effective form of contraception for the duration of the study and until 35 days after the final dose of ADI-PEG 20 or 180 days after the final dose of atezolizumab, pemetrexed or carboplatin, whichever is later.
- Negative serum or urine pregnancy test for female patients of childbearing potential within 14 days prior to cycle 1 day 1.
- Adequate normal organ, marrow and coagulation function within 28 days prior to cycle 1 day 1
- Willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow up.
Who cannot join
- Radiotherapy (including for palliative reasons) or targeted therapywithin four weeks before study treatment.
- History of autoimmune disease
- Ongoing toxic manifestations of previous treatments.
- Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery).
- Major thoracic or abdominal surgery from which the patient has not yet recovered.
- Serious infection requiring treatment with intravenous antibiotics at the time of study entrance, or an infection requiring intravenous therapy within 7 days prior to the first dose of study treatment.
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- Known to be serologically positive for human immunodeficiency virus (HIV).
- Known active hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- Uncontrolled serious intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, and social situations that would limit compliance with study requirements.
- Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow within 8 weeks of study treatment.
- Ongoing therapeutic anticoagulation (prophylactic dose low molecular weight heparin is acceptable).
- Concurrent treatment with other experimental drugs or participation in another interventional clinical study with therapeutic intent within 28 days from cycle 1 day 1. Participation in an observational or biomarker study would be acceptable, with prior Sponsor approval.
- Malignancies other than NSCLC within 5 years prior to study entry, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome.
- Prior treatment with cluster of differentiation 137 (CD137) agonists, anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins.
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation.
- Prior allogeneic stem cell or solid organ transplantation.
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- Active tuberculosis.
- Receipt of a live, attenuated vaccine within 4 weeks prior to cycle 1 day 1 or anticipation that a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months after the last dose of atezolizumab.
- Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1 day 1.
- Treatment with systemic corticosteroids or other systemic immunosuppressive medications
About this study
Official title: Phase I Study in Patients With Tumours Requiring Arginine to Assess ADI-PEG 20 With Atezolizumab, Pemetrexed and Carboplatin (ADIAtezoPemCarbo) (iTRAP Study)
iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung carcinoma (NSCLC) - stage IIIB/IV.
Read the detailed description
iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous NSCLC (stage IIIB/IV). Patients will initially receive 4 cycles of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin unless there is documented disease progression or unacceptable toxicities. On completion of 4 cycles and in the absence of disease progression requiring other therapeutic interventions, patients may receive additional cycles of ADI PEG20 and/or atezolizumab and/or pemetrexed for up to a maximum of 2 years at the discretion of the treating physician.
Dose escalation will occur using a 3 + 3 design. The trial will start at dose level 1, which represents 100% of the recommended dose of carboplatin (AUC5) and pemetrexed (500mg/m2) when given as a combination, 100% of the atezolizumab recommended dose (1200mg) and 50% of the recommended single agent dose of ADI PEG20 (18mg/m2). ADI PEG20 doses will be increased according to pre-planned dose escalations.
If the maximum tolerated dose (MTD) is reached with the first 6 patients, up to an additional 6 patients will be enrolled at the MTD. The MTD is defined as the dose level below that at which 2/3 or ≥3/6 patients experience a dose limiting toxicity (DLT).
The maximum administered dose (MAD) may also equal the MTD if dose escalation is stopped before two DLTs are observed at a given dose level due to the expectation that higher dose levels would be too toxic to administer to patients or the maximum planned dose level has been achieved.
The MTD will be determined following review of all the relevant toxicity data by the Safety Review Committee (SRC).
If dose level 1 equals the MAD then dose level -1 may be investigated with a 50% reduction in ADI PEG20 (9mg/m2) along with atezolizumab 1200mg, carboplatin AUC5, and pemetrexed 500mg/m2.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Atezolizumab, Pemetrexed, Carboplatin, ADI PEG20
- 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.
AtezolizumabDrug
Also called Tecentriq
Administered at a fixed dose of 1200 mg (equivalent to an average body weight-based dose of 15mg/kg) by intravenous (IV) infusion every 3 weeks (21 days).
PemetrexedDrug
Also called Alimta
Administered at a fixed dose of 500mg/m2 by IV infusion every 3 weeks.
CarboplatinDrug
Administered at a fixed dose of AUC5 by IV infusion every 3 weeks.
ADI PEG20Drug
Administered by intramuscular (IM) injection to patients once weekly.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level -1 | Experimental | Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 9mg/m2 Receives: Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: ADI PEG20 |
| Dose Level 1 | Experimental | Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 18mg/m2 Receives: Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: ADI PEG20 |
| Dose Level 2 | Experimental | Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 36mg/m2 Receives: Drug: Atezolizumab; Drug: Pemetrexed; Drug: Carboplatin; Drug: ADI PEG20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of dose limiting toxicities
Protocol defined haematological events attributed as possibly, probably or definitely related to the study treatment.
Measured: First 21 days of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2018
- Study start1 Jun 2018 (estimated)
- Primary completion31 Jan 2020 (estimated)
- Study completion31 Dec 2021 (estimated)
Why it stopped: Funder and IMP manufacturer withdrew support
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- Polaris Group, Hoffmann-La Roche
- Responsible party
- Sponsor
- Investigators
- Peter Szlosarek, Study chair, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03498222
- Sponsor's protocol ID
- 012375QM
- Acronym
- iTRAP
- Status last verified
- Feb 2020
- First submitted
- 6 Apr 2018
- Last updated
- 25 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study in Patients With Tumours Requiring Arginine to Assess ADI-PEG 20 With Atezolizumab, Pemetrexed and Carboplatin (ADIAtezoPemCarbo) (iTRAP Study)
- ClinicalTrials.gov ID
- NCT03498222
- Acronym / sponsor ID
- iTRAP / 012375QM
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funder and IMP manufacturer withdrew support
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- Polaris Group, Hoffmann-La Roche
- Study start
- 1 Jun 2018 (estimated)
- Primary completion
- 31 Jan 2020 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 13 Apr 2018 (actual)
- 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.
iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung carcinoma (NSCLC) - stage IIIB/IV.
Detailed description
iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous NSCLC (stage IIIB/IV). Patients will initially receive 4 cycles of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin unless there is documented disease progression or unacceptable toxicities. On completion of 4 cycles and in the absence of disease progression requiring other therapeutic interventions, patients may receive additional cycles of ADI PEG20 and/or atezolizumab and/or pemetrexed for up to a maximum of 2 years at the discretion of the treating physician.
Dose escalation will occur using a 3 + 3 design. The trial will start at dose level 1, which represents 100% of the recommended dose of carboplatin (AUC5) and pemetrexed (500mg/m2) when given as a combination, 100% of the atezolizumab recommended dose (1200mg) and 50% of the recommended single agent dose of ADI PEG20 (18mg/m2). ADI PEG20 doses will be increased according to pre-planned dose escalations.
If the maximum tolerated dose (MTD) is reached with the first 6 patients, up to an additional 6 patients will be enrolled at the MTD. The MTD is defined as the dose level below that at which 2/3 or ≥3/6 patients experience a dose limiting toxicity (DLT).
The maximum administered dose (MAD) may also equal the MTD if dose escalation is stopped before two DLTs are observed at a given dose level due to the expectation that higher dose levels would be too toxic to administer to patients or the maximum planned dose level has been achieved.
The MTD will be determined following review of all the relevant toxicity data by the Safety Review Committee (SRC).
If dose level 1 equals the MAD then dose level -1 may be investigated with a 50% reduction in ADI PEG20 (9mg/m2) along with atezolizumab 1200mg, carboplatin AUC5, and pemetrexed 500mg/m2.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level -1 | Experimental | Drug: Atezolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: ADI PEG20Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 9mg/m2 |
| Dose Level 1 | Experimental | Drug: Atezolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: ADI PEG20Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 18mg/m2 |
| Dose Level 2 | Experimental | Drug: Atezolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: ADI PEG20Atezolizumab 1200mg Pemetrexed 500mg/m2 Carboplatin AUC5 ADI PEG20 36mg/m2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Willing and able to provide written informed consent prior to study entry.
- Age ≥ 18 years.
- Histologically proven advanced non-squamous NSCLC (stage IIIB/IV) not treated with chemotherapy or immunotherapy - immunotherapy for uveal melanoma and prior (neo)adjuvant chemotherapy is permitted. Patients with EGFR mutant or ALK positive NSCLC must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial.
- ASS1 deficiency defined as ≤50% ASS expression on tissue specimen by immunohistochemistry (IHC) (cytospin samples are acceptable) - assessed centrally. For patients previously treated with (neo)adjuvant chemotherapy, this specimen may have been obtained before that chemotherapy.
- Measurable disease as assessed by RECIST 1.1 i.e. at least one lesion, not previously irradiated, that can be measured accurately at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements OR lytic or mixed (lytic + sclerotic) bone lesions in the absence of measurable disease as defined above; NOTE: patients with sclerotic / osteoblastic bone lesions only in the absence of measurable disease are not eligible)
Key exclusion criteria (22 listed)
- Radiotherapy (including for palliative reasons) or targeted therapywithin four weeks before study treatment.
- History of autoimmune disease
- Ongoing toxic manifestations of previous treatments.
- Symptomatic brain or spinal cord metastases (patients must be stable for > 3 months post radiotherapy or surgery).
- Major thoracic or abdominal surgery from which the patient has not yet recovered.
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 |
|---|---|---|
| AtezolizumabAlso: TecentriqAdministered at a fixed dose of 1200 mg (equivalent to an average body weight-based dose of 15mg/kg) by intravenous (IV) infusion every 3 weeks (21 days). | Drug | Dose Level -1, Dose Level 1, Dose Level 2 |
| PemetrexedAlso: AlimtaAdministered at a fixed dose of 500mg/m2 by IV infusion every 3 weeks. | Drug | Dose Level -1, Dose Level 1, Dose Level 2 |
| CarboplatinAdministered at a fixed dose of AUC5 by IV infusion every 3 weeks. | Drug | Dose Level -1, Dose Level 1, Dose Level 2 |
| ADI PEG20Administered by intramuscular (IM) injection to patients once weekly. | Drug | Dose Level -1, Dose Level 1, Dose Level 2 |
Primary outcome
Occurrence of dose limiting toxicities
Time frame: First 21 days of treatment
Protocol defined haematological events attributed as possibly, probably or definitely related to the study treatment.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2020.
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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.
Peter Szlosarek study chair
Queen Mary University of London
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atezolizumab, Pemetrexed and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Queen Mary University of London.
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 11 inclusion and 22 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: withdrawn, as of the sponsor's last update on 25 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
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 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.
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 withdrawn before enrolling participants, so there are no results.
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?
Occurrence of dose limiting toxicities (time frame: First 21 days of treatment). 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 25 Feb 2020.