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

NCT03361319 | Withdrawn Phase 1 DMC

• 1 other identifier: CCR 4448
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A PHASE I/II TRIAL OF COMBINATION NAB-PACLITAXEL AND NINTEDANIB OR NAB-PACLITAXEL AND PLACEBO IN RELAPSED NSCLC ADENOCARCINOMA

Conditions

NSCLC, Recurrent; Adenocarcinoma of Lung

Keywords

NSCLC; Non-Small Cell Lung Cancer; Adenocarcinoma of lung

Outcome Measures

Primary Outcomes (1)

• Part 1: Maximum Tolerated Dose

  To define Maximum tolerated dose (MTD) and evaluate incidence of dose-limiting toxicities (DLTs) during Cycle 1

  1 and 2 years from patients commencement

Secondary Outcomes (4)

• Part 1 and 2: Adverse Events Review

  4 years from Start date of trial

• Part 1 and 2: RECIST Response

  4 years from start date of trial

• Cycles Tolerated

  4 years from start date of trial

• Part 2: Overall Survival

  9 months post Chemotherapy

Other Outcomes (1)

• Part 2: Progression Free Survival

  12 weeks post first dose of treatment and ongoing until end of study

Study Arms (3)

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

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.

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

Drug: Vargatef; Drug: Abraxane; Other: placebo

Interventions

Vargatef DRUG

small molecule triple kinase inhibitor

Also known as: Nintedanib, L01xe31

Part 1: (Phase Ib) Dose Escalation; Part 1: Dose Expansion; Part 2: (Phase II)

Abraxane DRUG

Paclitaxel formulated as albumin bound nanoparticles

Also known as: Paclitaxel, L01CD01

Part 1: (Phase Ib) Dose Escalation; Part 1: Dose Expansion; Part 2: (Phase II)

placebo OTHER

Placebo in place of Ninedanib

Part 2: (Phase II)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Boehringer Ingelheim: collaborator
• Celgene: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence; Adenocarcinoma of Lung

Interventions

nintedanib; Albumin-Bound Paclitaxel; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Sanjay Popat

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 2 only of the study is double-blinded. 2 arms
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part I: A dose-escalation - standard 3+3 design. Part 2: A placebo-controlled, randomised, double-blind, 2-arms.

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: December 4, 2017
• Study Start: July 1, 2020
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: November 24, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share