Combination Nab-paclitaxel (N-P) and Nintedanib or N-P and Placebo in Relapsed NSCLC Adenocarcinoma

Learn more about:
Related Clinical Trial
A Study of IMU-201 (PD1-Vaxx), a B-Cell Immunotherapy, in Adults With Non-Small Cell Lung Cancer Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Icotinib for Completed Resected IB NSCLC With EGFR Mutation Circulating Tumor DNA in Patients at High Risk for Lung Cancer Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers Radiation Therapy, Chemotherapy, and Soy Isoflavones in Treating Patients With Stage IIIA-IIIB Non-Small Cell Lung Cancer Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer Erlotinib and Radiation Therapy Plus Combination Chemotherapy in Treating Patients With Inoperable Stage III Non-Small Cell Lung Cancer Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Advanced, Metastatic, or Recurrent Non-Small Cell Lung Cancer Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer Phase I IGART Study Using Active Breathing Control and Simultaneous Boost for Patients With NSCLC Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery Bevacizumab, Paclitaxel, Carboplatin, and Radiation Therapy to the Chest in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery QUILT-3.017: Study of NEO-201 in Solid Tumors Photodynamic Therapy in Treating Patients With Lung Cancer Vaccine Treatment for Advanced Non-Small Cell Lung Cancer S1300: Pemetrexed Disodium With or Without Crizotinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer That Has Progressed After Crizotinib Single Agent Chemotherapy +/- Nivolumab in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor Comparison of Different Types of Surgery in Treating Patients With Early-stage Non-small Cell Lung Cancer Therapeutic ResistAnce and Clonal Evolution Assessed With Liquid Biopsy of NSCLC Patients in China ALK/ROS1/MET Mutations on Plasma ctDNA in Patients With NSCLC The Tracking Molecular Evolution for NSCLC (T-MENC) Study Phase 1a/1b Study of TPST-1495 Alone and With Pembrolizumab in Subjects With Solid Tumors An Integrated Approach to Treating Recurrent Thoracic Carcinomas Resistant to Tyrosine Kinase Inhibitors Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer LMB-100 Followed by Pembrolizumab in the Treatment of Adults With Mesothelin-Expressing Non-Squamous Non-Small Cell Lung Cancer (NSCLC) P2 of RMT in Combo w Durvalumab or Durva + Chemo in Untreated Adenocarcinoma NSCLC Feasibility and Safety of Nintedanib in Combination With Nivolumab in Pretreated Patients With Advanced or Metastatic NSCLC of Adenocarcinoma Histology Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer Combination Nab-paclitaxel (N-P) and Nintedanib or N-P and Placebo in Relapsed NSCLC Adenocarcinoma Prospective Radiological Study of HRCT to Predict Pathological Noninvasiveness in NSCLC To Compare Efficacy and Safety of CT-P16 and EU-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer Hsp90 Inhibitor AUY922 and Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV Non-Small Cell Lung Cancer Impact of Concomitant Genetic Alterations in EGFR Mutated Adenocarcinoma by NGS Analysis: A Multicenter Study Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With Advanced NSCLC Poziotinib in Stage IV Lung Adenocarcinoma With HER2 Mutation (KASTT001) Study of Nivolumab in Combination With GM.CD40L Vaccine in Adenocarcinoma of the Lung Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung Lung Cancer Mutation Consortium Protocol The Detection of EGFR Mutations in Liquid Based Cytology Samples NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma A Safety and Efficacy Study of Farletuzumab in Subjects With Adenocarcinoma of the Lung Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03) Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma The Study of Apatinib Plus CIK as the Third Line Therapy for Advanced Lung Adenocarcinoma Patients With Wild-Type EGFR Telomere Biology in Early Adenocarcinoma of the Lung

Brief Title

Combination Nab-paclitaxel (N-P) and Nintedanib or N-P and Placebo in Relapsed NSCLC Adenocarcinoma

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

Brief Summary

      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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Part 1: Maximum Tolerated Dose

Secondary Outcome

 Part 1 and 2: Adverse Events Review

Condition

NSCLC, Recurrent

Intervention

Vargatef

Study Arms / Comparison Groups

 Part 1: (Phase Ib) Dose Escalation
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

194

Start Date

July 2020

Completion Date

July 2023

Primary Completion Date

July 2023

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  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.

        Exclusion Criteria:

          -  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).

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Sanjay Popat, 02089156667, [email protected]



Administrative Informations


NCT ID

NCT03361319

Organization ID

CCR 4448


Responsible Party

Sponsor

Study Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

 Boehringer Ingelheim

Study Sponsor

Sanjay Popat, Principal Investigator, Royal Marsden NHS Foundation Trust


Verification Date

May 2020