Efficacy and Safety of Nintedanib Combined With Paclitaxel Chemotherapy for Patients With BRAF wt Metastatic Melanoma

NCT02308553 | Completed Phase 1

• 1 other identifier: Nipawilma_2013
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 10

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled phase I/II trial designed to characterize the safety and estimate the efficacy of nintedanib when combined with paclitaxel chemotherapy compared with paclitaxel chemotherapy alone in patients with BRAF wild type metastatic melanoma not previously treated with taxanes or kinase inhibitors.

Conditions

Cutaneous Malignant Melanoma

Keywords

BRAF V600 wildtype; cutaneous malignant melanoma; nintedanib; paclitaxel; kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS)

  Time from administration of first study drug to the date of first documented progression or death due to any cause, whichever occurs first

  12 months after LPI

Secondary Outcomes (3)

• Overall survival

  12 months after LPI

• Safety and toxicity (graded according to CTCAE, Version 4.0)

  12 months after LPI

• Quality of Life (EORTC QLQ-C30)

  12 months after LPI

Study Arms (2)

Nintedanib + Paclitaxel

EXPERIMENTAL

Nintedanib (150 or 200mg BID) for up to 48 weeks combined with paclitaxel 90mg/m2 BSA day 1, 8, 15 q28 days for a maximum of 6 courses

Drug: Nintedanib; Drug: Paclitaxel

Nintedanib-Placebo + Paclitaxel

PLACEBO COMPARATOR

Placebo (150 or 200mg BID) for up to 48 weeks combined with paclitaxel 90mg/m2 BSA day 1, 8, 15 q28 days for a maximum of 6 courses

Drug: Nintedanib-Placebo; Drug: Paclitaxel

Interventions

Nintedanib DRUG

Nintedanib (150 mg or 200 mg BID)

Also known as: Vargatef

Nintedanib + Paclitaxel

Nintedanib-Placebo DRUG

Placebo (150 mg or 200 mg BID)

Nintedanib-Placebo + Paclitaxel

Paclitaxel DRUG

Paclitaxel as 90mg/mw infusion day 1, 8, 15 q28 (6 cycles)

Also known as: Taxomedac

Nintedanib + Paclitaxel; Nintedanib-Placebo + Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, (surgically incurable or unresectable) stage III or IV, BRAF V600 wildtype metastatic cutaneous malignant melanoma.
• Written informed consent
• A minimum of 1 measurable lesion according to RECIST v1.1 criteria.
• ECOG of 0-1.
• Adequate hematologic, renal and liver function within 14 days prior to initiation of dosing:
• Hematologic:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Hemoglobin ≥ 9 g/dL (5.6 mmol/L; Subjects may not have had a transfusion within 7 days of screening assessment)
• Platelets: ≥ 100 x 109/L
• Hepatic
• Total bilirubin: ≤ 1.0 x ULN
• AST and ALT: ≤ 1.5 x ULN (In the case of liver metastases: 2.5 x ULN)
• Renal o Serum creatinine: ≤ 1.5 mg/dL (133 µmol/L) or, if greater than 1.5 mg/dL: Calculated creatinine clearance: ≥ 50 mL/min
• effective method of contraception for at least 3 months after completion of nintedanib/placebo monotherapy as directed by their physician.
• Men should use an effective method of contraception during treatment and for at least 6 months after completion of paclitaxel treatment and for at least 3 months after completion of nintedanib/placebo monotherapy as directed by their physician.

You may not qualify if:

• Prior systemic therapy with taxanes or kinase inhibitors. Any prior therapy for metastatic disease must have been discontinued at least 4 weeks prior to initiation of dosing.
• Major surgery or radiation therapy within 4 weeks of starting the study treatment (minor surgical procedures such as biopsies are allowed, however patients must have recovered).
• Known inherited predisposition to bleeding or thrombosis and therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid \< 325mg per day)
• Patients with the following coagulation parameters will be excluded:
• International normalised ratio (INR) \> 2
• Prothrombin time (PT) and partial thromboplastin time (PTT): \> 50% of deviation of institutional ULN
• History of clinically significant haemorrhagic or thromboembolic event in the past 6 months
• NCI CTCAE (V4.0) grade 3 hemorrhage within 4 weeks of starting the study treatment.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.
• Serious, non-healing wound, ulcer, or bone fracture.
• Known CNS disease:
• Previous Grade 2 or higher sensory neuropathy.
• History of or known spinal cord compression, or carcinomatous meningitis, or evidence of active brain metastases (e.g. 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 one month before randomization) or leptomeningeal disease on screening CT or MRI scan.
• Any of the following within the 6 months prior to enrolment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.

Sponsors & Collaborators

• Prof. Dr. med. Dirk Schadendorf: lead
• Boehringer Ingelheim: collaborator
• medac GmbH: collaborator
• Alcedis GmbH: collaborator

Study Sites (10)

University Hospital Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Elbeklinikum Buxtehude

Buxtehude, 21614, Germany

Location

SRH Wald-Klinikum Gera

Gera, 07548, Germany

Location

National Centre for Tumour Diseases (NCT)

Heidelberg, 69120, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, 67063, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, 23538, Germany

Location

University Hospital München

München, 80337, Germany

Location

University Hospital Münster

Münster, 48149, Germany

Location

Fachklinik Hornheide

Münster, 48157, Germany

Location

MeSH Terms

Conditions

Melanoma, Cutaneous Malignant

Interventions

nintedanib; Paclitaxel

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Dirk Schadendorf, Prof. Dr.

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med. Dirk Schadendorf

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: March 17, 2015
• Primary Completion: October 17, 2019
• Study Completion: November 1, 2019
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)