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Cutaneous Malignant MelanomaPhase 1/2NIPAWILMANCT02308553

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

A Phase 1/2 study testing Nintedanib and Paclitaxel in people with Cutaneous Malignant Melanoma, run by Prof. Dr. med. Dirk Schadendorf at 10 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cutaneous Malignant Melanoma
What is being tested?
Nintedanib and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
33 participants
Where
10 sitesGermany
Study dates
17 Mar 2015to Nov 2019
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

  • 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:
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  • 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.
  • Patients must have recovered from all prior treatment-related toxicities to NCI CTCAE (v4.0) Grade of 0 or 1, except for toxicities not considered a safety risk such as alopecia.
  • Male or female, aged 18 years or older
  • Life expectancy at least 3 months

Who cannot join

  • 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
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  • 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.
  • Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2.
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
  • Symptomatic peripheral vascular disease.
  • Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
  • Known hypersensitivity reaction to any of the components of study treatment (e.g. contrast media) or other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
  • Previous cancer (unless a RFS interval of at least 5 years) with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin.
  • Known clinically uncontrolled infectious disease including HIV positivity or AIDS-related illness and active or chronic hepatitis C and/or B infection.
  • Pregnancy (absence to be confirmed by ß-hCG test) or lactation period.
  • Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule
  • Active alcohol or drug abuse
  • Treatment with other investigational drugs or treatments in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial.
  • Legal incapacity or limited legal capacity
  • Significant weight loss (> 10% of body weight) within past 6 months prior to inclusion into the trial

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • Elbeklinikum Buxtehude

    Buxtehude, 21614

  • University Hospital Essen

    Essen, North Rhine-Westphalia, 45147

  • SRH Wald-Klinikum Gera

    Gera, 07548

  • National Centre for Tumour Diseases (NCT)

    Heidelberg, 69120

  • Universitätsklinikum des Saarlandes

    Homburg, 66421

  • Universitätsklinikum Schleswig-Holstein, Campus Lübeck

    Lübeck, 23538

  • Klinikum der Stadt Ludwigshafen am Rhein gGmbH

    Ludwigshafen, 67063

  • University Hospital München

    München, 80337

  • University Hospital Münster

    Münster, 48149

  • Fachklinik Hornheide

    Münster, 48157

Other trials in Germany

About this study

Official title: Phase I/II,Multicenter,Randomized,Double-blind,Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib/Vargatef in Combination With Paclitaxel Chemotherapy for Treatment of Patients With BRAF Wildtype Metastatic Melanoma

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.

Read the detailed description

Study Phase I: Run-In-Phase Based on acceptable safety data for nintedanib monotherapy, a rapid dose finding will be conducted in a classical 3+3 design. Predefined dose levels are 150 mg (dose level 1) and 200 mg (dose level 2) nintedanib, twice daily, with weekly paclitaxel 90 mg/m2.

Study Phase II Patients with advanced (unresectable Stage III or IV) BRaf V600 wild type melanoma (n=120) will be randomized (1:1) to receive either Nintedanib (150 or 200 mg BID depending on results of phase I) in combination with paclitaxel or Placebo in combination with paclitaxel.

Total study duration per patient: approximately 12 months of therapy + Follow up until end of study

All patients enrolled in either phase I or phase II will be treated according to the following treatment plan:

Week 1 - 24:

Chemotherapy with paclitaxel combined with nintedanib/placebo

Week 25 - 48:

Extended monotherapy with nintedanib/placebo

Week 52 (or approximately 4 weeks after last treatment dose):

End of Treatment visit

Follow up:

After end of treatment the survival, disease status and further therapies of each patient will be assessed every 3 months until death, progression of disease or end of study whichever occurs first

Being tested
Nintedanib, Nintedanib-Placebo, Paclitaxel
Keywords
BRAF V600 wildtype, cutaneous malignant melanoma, nintedanib, paclitaxel, kinase inhibitor
Medical subject headings
Melanoma, Cutaneous Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NintedanibDrug

    Also called Vargatef

    Nintedanib (150 mg or 200 mg BID)

  • Nintedanib-PlaceboDrug

    Placebo (150 mg or 200 mg BID)

  • PaclitaxelDrug

    Also called Taxomedac

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

Study groups in NCT02308553
Study groupRoleWhat they receive
Nintedanib + PaclitaxelExperimentalNintedanib (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
Receives: Drug: Nintedanib; Drug: Paclitaxel
Nintedanib-Placebo + PaclitaxelPlacebo comparatorPlacebo (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
Receives: Drug: Nintedanib-Placebo; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 12 months after LPI

Secondary outcomes (3)

  1. Overall survival

    Time from the date of first administration of study drug to the date of death due to any cause.

    Measured: 12 months after LPI

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

    Reporting of adverse events from the date of first administration of study drug until 30 days after last administration of study drug

    Measured: 12 months after LPI

  3. Quality of Life (EORTC QLQ-C30)

    Quality of life during therapy (i.e. until end of treatment visit)

    Measured: 12 months after LPI

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2014 (estimated)
  2. Study start17 Mar 2015
  3. Primary completion17 Oct 2019
  4. Study completionNov 2019

Resources

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
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02308553
Sponsor's protocol ID
Nipawilma_2013
Acronym
NIPAWILMA
Status last verified
Oct 2020
First submitted
2 Dec 2014
Last updated
14 Oct 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nintedanib and Paclitaxel in people with Cutaneous Malignant Melanoma, run by Prof. Dr. med. Dirk Schadendorf at 10 sites in Germany.

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 18 inclusion and 28 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: finished, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

progression-free survival (PFS) (time frame: 12 months after LPI). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02308553.

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 14 Oct 2020.

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