NSCLC, RecurrentPhase 1/2N3NCT03361319
Combination Nab-paclitaxel (N-P) and Nintedanib or N-P and Placebo in Relapsed NSCLC Adenocarcinoma
A Phase 1/2 study testing Vargatef and Abraxane in people with NSCLC, Recurrent and Adenocarcinoma of Lung, run by Royal Marsden NHS Foundation Trust.
Trial summary
A PHASE I/II TRIAL OF COMBINATION NAB-PACLITAXEL AND NINTEDANIB OR NAB-PACLITAXEL AND PLACEBO IN RELAPSED NSCLC ADENOCARCINOMA Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Recurrent, Adenocarcinoma of Lung
- What is being tested?
- Vargatef and Abraxane
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2020to Jul 2023
- Phase
- Phase 1/2
- 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
- Male or female patients aged 18 or over.
- Patients with a pathologically confirmed diagnosis of stage IIIb or stage IV adenocarcinoma of the lung; patients with locally recurrent disease (stage IIIa) and no radical treatment options are also eligible.
- Patients who have previously received no more than 2 lines of systemic therapy for NSCLC with palliative intent:
- Chemotherapy as first or second line with palliative intent
- Relapsing within 6 months of adjuvant chemotherapy after surgery or as part of radical chemo-radiotherapy, which count as one line of therapy
- Licenced or experimental maintenance therapy is allowed (e.g. pemetrexed)
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- Immunotherapy at prior line of treatment (first or second line) is allowed.
- Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Patients with estimated life expectancy of ≥ 12 weeks.
- Patients with at least one radiologically measurable tumour lesion as defined by RECIST 1.1 criteria.
- Patients with adequate haematopoietic, hepatic and renal function.
- Signed informed consent in accordance with local legislation.
Who cannot join
- Patients with a known EGFR kinase sensitising mutation or ALK gene fusion prior to enrolment who have not received prior TKI (patients enrolled and subsequently found to be positive will remain on protocol). Patients with known EGFR activating mutation or ALK fusion who have received appropriate TKI treatment will be allowed.
- Any concurrent anticancer systemic therapy.
- Prior treatment with nintedanib or any other VEGFR inhibitor; prior treatment with bevacizumab is allowed
- Patients refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant setting does not exclude eligibility provided there is no disease recurrence within 12 months upon completion of chemotherapy in that setting.
- Inadequate laboratory parameters defined by:
- Absolute neutrophil count (ANC) < 1,500/μl (1.5x109/L).
Show all 36Show fewer
- Platelets < 100,000/μl (100x109/L).
- Haemoglobin < 9.0 g/dl or requiring transfusions.
- Creatinine clearance < 45 ml/min (by local institutional methods).
- Total bilirubin outside normal limits:
- ALT and/or AST > 1.5 x ULN in patients without liver metastasis.
- ALT and/or AST > 2.5 x ULN in patients with liver metastasis.
- International normalised ratio (INR) > 2, prothrombin time (PT) and partial thromboplastin time (PTT) > 50% of deviation of institutional ULN.
- Proteinuria CTCAE grade 2 or greater.
- Pre-existing peripheral sensory neuropathy CTCAE grade 2 or greater.
- Use of any investigational drug within 4 weeks of randomisation.
- Radiotherapy within 4 weeks prior to randomisation.
- Major surgery (other than biopsy) within 4 weeks prior to randomisation.
- Active brain metastases or leptomeningeal disease (defined as stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least 4 weeks prior to randomisation).
- Any other active current malignancy (other than non-melanomatous skin cancer, in situ breast or in situ cervical cancer, prostate cancer diagnosed more than 3 years prior, or breast cancer diagnosed more than 5 year prior to randomisation).
- Active or uncontrolled infections or serious illnesses or medical conditions that in the opinion of the investigator could interfere with the patient's participation in the study, including:
- Known active or chronic hepatitis C and/or B infection.
- Known pre-existing interstitial lung disease or pneumonitis
- Presence of significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion).
- Gastro-intestinal abnormalities, including inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption, any medical co-morbidity affecting gastrointestinal absorption.
- History of clinically significant haemorrhagic or thromboembolic event in the past 6 months.
- Known inherited predisposition to bleeding or thrombosis.
- Major injuries within the past 10 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
- Drug or alcohol abuse.
- Therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of indwelling intravenous device) or anti-platelet therapy (except low dose therapy with acetylsalicylic acid <325mg her day).
- Radiographic evidence (CT or MRI) of cavitary or necrotic tumours or local invasion of major blood vessels by tumour.
- Pregnancy or breast feeding; female patients must have a negative pregnancy test (beta-HCG test in urine or serum) prior to commencing study treatment.
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for at least three months after ceasing study therapy (medically acceptable methods of contraception include total true abstinence*, permanent sterilisation (see section 7.1.4), combined oral, transdermal or intra-vaginal hormonal contraceptives, methoxyprogesterone injections (e.g. Depo-provera), copper-banded intra-uterine devices, hormone-impregnated intra-uterine systems and vasectomised partners; all methods of contraception, with the exception of total abstinence, should be used in combination with the use of a condom by male sexual partners).
- Known hypersensitivity or any contraindications to the trial drugs, including nab-paclitaxel/nintedanib, to their excipients or to contrast media or other ingredients including peanuts and soya.
- Patients unable to comply with the protocol.
- True abstinence, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMP, and withdrawal are not acceptable methods of contraception.
About this study
Official title: A Phase I Trial of Combination Nab-Paclitaxel and Nintedanib or Nab-paclitaxel and Placebo in Relapsed Non-Small Cell Lung Cancer Adenocarcinoma
A PHASE I/II TRIAL OF COMBINATION NAB-PACLITAXEL AND NINTEDANIB OR NAB-PACLITAXEL AND PLACEBO IN RELAPSED NSCLC ADENOCARCINOMA
Read the detailed description
The study is divided into 2 parts: Part 1 is the Phase Ib portion of the trial and Part 2 is the Phase II portion of the trial. Once the Trial Steering Committee has completed the dose limiting toxicity (DLT) assessment for Part 1 and confirmed RP2D for Part 2, Part 2 enrolment will proceed. The objective(s) for each part are as follows:
Part 1: The objective of Part 1 is to evaluate the safety and tolerability of combination nab-paclitaxel and nintedanib in patients with stage IIIb and IV adenocarcinoma of the lung in second and third treatment line setting and to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of nintedanib when given with nab-paclitaxel at 100mg/m2 d1, d8 q21.
Part 2: The primary objective of Part 2 is to explore the efficacy of combination nab-paclitaxel and nintedanib versus nab-paclitaxel and placebo in the same patient population, with nintedanib/placebo given at the recommended phase 2 dose (RP2D) as defined during part 1 of the study.
- Conditions
- NSCLC, Recurrent, Adenocarcinoma of Lung
- Being tested
- Vargatef, Abraxane, placebo
- Keywords
- NSCLC, Non-Small Cell Lung Cancer, Adenocarcinoma of lung
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Recurrence, Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VargatefDrug
Also called Nintedanib, L01xe31
small molecule triple kinase inhibitor
AbraxaneDrug
Also called Paclitaxel, L01CD01
Paclitaxel formulated as albumin bound nanoparticles
placeboOther
Placebo in place of Ninedanib
| Study group | Role | What they receive |
|---|---|---|
| Part 1: (Phase Ib) Dose Escalation | Experimental | A dose-finding study of nintedanib (Vargatef) with nab-paclitaxel (Abraxane) with a standard 3+3 design. In the dose escalation part there will be 3 dose cohorts of nintedanib:
Dose level -1: 100mg po BID d2-7, 9-21, q21 Dose level 1: 150mg po BID d2-7, 9-21, q21 Dose level 2: 200mg po BID d2-7, 9-21, q21 Receives: Drug: Vargatef; Drug: Abraxane |
| Part 1: Dose Expansion | Experimental | In the dose expansion part, 6 additional patients will be enrolled at the maximum tolerated dose (MTD) of nintedanib (Vargatef) with nab-paclitaxel (Abraxane), prior to proceeding to part 2. Receives: Drug: Vargatef; Drug: Abraxane |
| Part 2: (Phase II) | Placebo comparator | A placebo-controlled, randomised, double-blind, 2-arm, phase 2 multi-centre clinical trial of nab-paclitaxel (Abraxane) with nintedanib (Vargatef) and nab-paclitaxel alone.
Arm A: nab-paclitaxel + placebo Arm B: nab-paclitaxel + nintedanib Receives: Drug: Vargatef; Drug: Abraxane; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Maximum Tolerated Dose
To define Maximum tolerated dose (MTD) and evaluate incidence of dose-limiting toxicities (DLTs) during Cycle 1
Measured: 1 and 2 years from patients commencement
Secondary outcomes (4)
Part 1 and 2: Adverse Events Review
To examine the frequency of all Adverse Events graded by NCI-CTCAE version 4.0
Measured: 4 years from Start date of trial
Part 1 and 2: RECIST Response
To examine the objective tumour response according to RECIST 1.1
Measured: 4 years from start date of trial
Cycles Tolerated
To define the number of cycles of nab-paclitaxel with nintedanib given
Measured: 4 years from start date of trial
Part 2: Overall Survival
To examine overall survival in the ITT and predefined subgroups (PD pre/post 9 months from start of first line chemotherapy; prior or no prior immunotherapy).
Measured: 9 months post Chemotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2017
- Study startJul 2020 (estimated)
- Primary completionJul 2023 (estimated)
- Study completionJul 2023 (estimated)
Why it stopped: Withdrawal of financial support from funder
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLC, RecurrentStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Part I: A dose-escalation - standard 3+3 design. Part 2: A placebo-controlled, randomised, double-blind, 2-arms.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Boehringer Ingelheim, Celgene
- Responsible party
- Sponsor
- Investigators
- Sanjay Popat, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03361319
- Sponsor's protocol ID
- CCR 4448
- Acronym
- N3
- Status last verified
- Nov 2020
- First submitted
- 22 Nov 2017
- Last updated
- 24 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Combination Nab-Paclitaxel and Nintedanib or Nab-paclitaxel and Placebo in Relapsed Non-Small Cell Lung Cancer Adenocarcinoma
- ClinicalTrials.gov ID
- NCT03361319
- Acronym / sponsor ID
- N3 / CCR 4448
- Conditions
- NSCLC, Recurrent, Adenocarcinoma of Lung
- Keywords
- NSCLC, Non-Small Cell Lung Cancer, Adenocarcinoma of lung
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Withdrawal of financial support from funder
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Boehringer Ingelheim, Celgene
- Study start
- Jul 2020 (estimated)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- Jul 2023 (estimated)
- First posted
- 4 Dec 2017 (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.
A PHASE I/II TRIAL OF COMBINATION NAB-PACLITAXEL AND NINTEDANIB OR NAB-PACLITAXEL AND PLACEBO IN RELAPSED NSCLC ADENOCARCINOMA
Detailed description
The study is divided into 2 parts: Part 1 is the Phase Ib portion of the trial and Part 2 is the Phase II portion of the trial. Once the Trial Steering Committee has completed the dose limiting toxicity (DLT) assessment for Part 1 and confirmed RP2D for Part 2, Part 2 enrolment will proceed. The objective(s) for each part are as follows:
Part 1: The objective of Part 1 is to evaluate the safety and tolerability of combination nab-paclitaxel and nintedanib in patients with stage IIIb and IV adenocarcinoma of the lung in second and third treatment line setting and to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of nintedanib when given with nab-paclitaxel at 100mg/m2 d1, d8 q21.
Part 2: The primary objective of Part 2 is to explore the efficacy of combination nab-paclitaxel and nintedanib versus nab-paclitaxel and placebo in the same patient population, with nintedanib/placebo given at the recommended phase 2 dose (RP2D) as defined during part 1 of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Part I: A dose-escalation - standard 3+3 design. Part 2: A placebo-controlled, randomised, double-blind, 2-arms.
| Arm | Type | Receives |
|---|---|---|
| Part 1: (Phase Ib) Dose Escalation | Experimental | Drug: Vargatef, Drug: AbraxaneA dose-finding study of nintedanib (Vargatef) with nab-paclitaxel (Abraxane) with a standard 3+3 design. In the dose escalation part there will be 3 dose cohorts of nintedanib: Dose level -1: 100mg po BID d2-7, 9-21, q21 Dose level 1: 150mg po BID d2-7, 9-21, q21 Dose level 2: 200mg po BID d2-7, 9-21, q21 |
| Part 1: Dose Expansion | Experimental | Drug: Vargatef, Drug: AbraxaneIn the dose expansion part, 6 additional patients will be enrolled at the maximum tolerated dose (MTD) of nintedanib (Vargatef) with nab-paclitaxel (Abraxane), prior to proceeding to part 2. |
| Part 2: (Phase II) | Placebo comparator | Drug: Vargatef, Drug: Abraxane, Other: placeboA placebo-controlled, randomised, double-blind, 2-arm, phase 2 multi-centre clinical trial of nab-paclitaxel (Abraxane) with nintedanib (Vargatef) and nab-paclitaxel alone. Arm A: nab-paclitaxel + placebo Arm B: nab-paclitaxel + nintedanib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female patients aged 18 or over.
- Patients with a pathologically confirmed diagnosis of stage IIIb or stage IV adenocarcinoma of the lung; patients with locally recurrent disease (stage IIIa) and no radical treatment options are also eligible.
- Patients who have previously received no more than 2 lines of systemic therapy for NSCLC with palliative intent:
- Chemotherapy as first or second line with palliative intent
- Relapsing within 6 months of adjuvant chemotherapy after surgery or as part of radical chemo-radiotherapy, which count as one line of therapy
Key exclusion criteria (36 listed)
- Patients with a known EGFR kinase sensitising mutation or ALK gene fusion prior to enrolment who have not received prior TKI (patients enrolled and subsequently found to be positive will remain on protocol). Patients with known EGFR activating mutation or ALK fusion who have received appropriate TKI treatment will be allowed.
- Any concurrent anticancer systemic therapy.
- Prior treatment with nintedanib or any other VEGFR inhibitor; prior treatment with bevacizumab is allowed
- Patients refractory to prior taxane therapy for advanced disease. Prior taxane used in the adjuvant setting does not exclude eligibility provided there is no disease recurrence within 12 months upon completion of chemotherapy in that setting.
- Inadequate laboratory parameters defined by:
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 |
|---|---|---|
| VargatefAlso: Nintedanib, L01xe31small molecule triple kinase inhibitor | Drug | Part 1: (Phase Ib) Dose Escalation, Part 1: Dose Expansion, Part 2: (Phase II) |
| AbraxaneAlso: Paclitaxel, L01CD01Paclitaxel formulated as albumin bound nanoparticles | Drug | Part 1: (Phase Ib) Dose Escalation, Part 1: Dose Expansion, Part 2: (Phase II) |
| placeboPlacebo in place of Ninedanib | Other | Part 2: (Phase II) |
Primary outcome
Part 1: Maximum Tolerated Dose
Time frame: 1 and 2 years from patients commencement
To define Maximum tolerated dose (MTD) and evaluate incidence of dose-limiting toxicities (DLTs) during Cycle 1
4 secondary outcomes
Part 1 and 2: Adverse Events Review
Time frame: 4 years from Start date of trial
Part 1 and 2: RECIST Response
Time frame: 4 years from start date of trial
Cycles Tolerated
Time frame: 4 years from start date of trial
Part 2: Overall Survival
Time frame: 9 months post Chemotherapy
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 24 Nov 2020.
- 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.
Sanjay Popat principal investigator
Royal Marsden NHS Foundation Trust
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vargatef and Abraxane in people with NSCLC, Recurrent and Adenocarcinoma of Lung, run by Royal Marsden NHS Foundation Trust.
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 12 inclusion and 36 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 24 Nov 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
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 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?
Part 1: Maximum Tolerated Dose (time frame: 1 and 2 years from patients commencement). 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 24 Nov 2020.