Skip to content

Nintedanib in Treating Patients With Malignant Pleural Mesothelioma That Is Recurrent

A Phase II Trial of BIBF 1120 (Nintedanib) in Recurrent Malignant Pleural Mesothelioma

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02568449
Enrollment
20
Registered
2015-10-05
Start date
2016-03-15
Completion date
2018-06-26
Last updated
2021-12-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Recurrent Pleural Malignant Mesothelioma, Stage IV Pleural Mesothelioma

Brief summary

This phase II trial studies how well nintedanib works in treating patients with malignant pleural mesothelioma that has come back. Nintedanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. To assess the 4-month progression-free survival (PFS) in patients with recurrent, unresectable malignant pleural mesothelioma (MAM) treated with nintedanib. SECONDARY OBJECTIVES: I. To assess response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in the subset of patients with measurable disease by both RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria and Modified RECIST criteria for pleural tumors. II. To assess overall survival. III. To evaluate the frequency and severity of toxicities associated with this treatment regimen. IV. To collect tissue samples for future correlative studies related to overall study objectives. OUTLINE: Patients receive nintedanib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Interventions

DRUGNintedanib

Given PO

Sponsors

National Cancer Institute (NCI)
CollaboratorNIH
Barbara Ann Karmanos Cancer Institute
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Patients must have histologically confirmed diagnosis of unresectable malignant pleural mesothelioma * Patients must have measurable or non-measurable disease documented by computed tomography (CT) scan; measurable disease must be assessed within 28 days prior to registration; non-measurable disease must be assessed within 42 days prior to registration; the CT from a combined positron emission tomography (PET)/CT must not be used to document measurable disease unless it is of diagnostic quality; all disease must be assessed by RECIST and modified RECIST criteria * Patients must have had prior systemically administered platinum-based chemotherapy; pleural space washing with cisplatin does not constitute systemic administration; no more than two prior systemic therapeutic regimens are allowed (including biologics, targeted and immunotherapies), and at least one regimen must have been platinum-based; neoadjuvant and/or adjuvant systemic therapy will not be counted as a prior regimen, assuming at least 12 weeks have elapsed between the end of neoadjuvant/adjuvant therapy and development of progressive disease; patients must have completed systemic therapy (including any chemotherapy, biologics, targeted and immunotherapies) \>= 28 days (42 days for nitrosoureas or mitomycin C) prior to registration and have recovered from adverse events due to agents administered * No prior treatment with BIBF 1120 or any other vascular endothelial growth factor receptor (VEGFR) inhibitor * No known hypersensitivity to BIBF 1120, to its excipients or to contrast media * Patients may have received prior surgery (e.g., pleurectomy) provided that at least 28 days have elapsed since surgery (thoracic or other major surgeries) and patients have recovered from all associated toxicities at the time of registration; there must be no anticipated need for major surgical procedures during protocol treatment * No 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); no leptomeningeal disease * No radiographic evidence of cavitary or necrotic tumors * No centrally located tumors with radiographic evidence (CT or magnetic resonance imaging \[MRI\]) of local invasion of major blood vessels * Institutions must offer patients the opportunity to submit tissue for future correlative studies * Patients may have received prior radiation therapy provided that at least 14 days have elapsed since the last treatment and patients have recovered from all associated toxicities at the time of registration * Patients must have a Zubrod performance status of 0-1 * Absolute neutrophil count (ANC) \>= 1,500/mcl * Platelet count \>= 100,000/mcl * Serum bilirubin =\< institutional upper limit of normal (IULN) * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) must be =\< 1.5 x IULN; for patients with liver metastasis, NO total bilirubin outside of normal limits, and NO ALT or AST \> 2.5 ULN * Serum creatinine =\< 1.5 x IULN or a calculated or measured creatinine clearance \>= 50 mL/min using the following formula: calculated creatinine clearance = (140-age) x wt (weight) (kg) x 0.85 (if female)/72 x creatinine (mg/dl); these tests (including creatinine \[mg/dl\] if using calculated creatinine clearance) must be obtained within 14 days prior to registration * No proteinuria Common Terminology Criteria For Adverse Events (CTCAE) grade 2 or greater * No therapeutic anticoagulation (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous device) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid \< 325mg per day); no history of clinically significant haemorrhagic or thromboembolic event in the past 6 months * Patients must have no evidence of bleeding diathesis or coagulopathy; patients must have no pathologic condition other than mesothelioma that carries a high risk of bleeding * No 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 * Patients must not have gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for intravenously (IV) alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease * No 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 \[New York Heart Association Class\] II, serious cardiac arrhythmia, pericardial effusion) * No active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy * No active or chronic hepatitis C and/or B infection * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years * No psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule * No active alcohol or drug abuse * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Design outcomes

Primary

MeasureTime frameDescription
Progression-free Survival (PFS)From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause; assessed up to 4 monthsPFS will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).

Secondary

MeasureTime frameDescription
Incidence of Grade 3-4 ToxicityUp to 1 yearNumber of participants with grade 3 or grade 4 for each type of toxicity encountered, using all toxicity evaluable patients.
Overall SurvivalUp to 1 yearOverall survival will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).
Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)Up to 1 yearnumber of participants responded (complete response, partial response, stable disease, progressive disease, not evaluable) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)

Countries

United States

Participant flow

Participants by arm

ArmCount
Treatment (Nintedanib)
Patients receive nintedanib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Nintedanib: Given PO
20
Total20

Baseline characteristics

CharacteristicTreatment (Nintedanib)
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
16 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
Age, Continuous70 years
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
0 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
20 Participants
Region of Enrollment
United States
20 participants
Sex: Female, Male
Female
2 Participants
Sex: Female, Male
Male
18 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
15 / 20
other
Total, other adverse events
20 / 20
serious
Total, serious adverse events
12 / 20

Outcome results

Primary

Progression-free Survival (PFS)

PFS will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).

Time frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause; assessed up to 4 months

ArmMeasureValue (MEDIAN)
Treatment (Nintedanib)Progression-free Survival (PFS)1.8 months
Secondary

Incidence of Grade 3-4 Toxicity

Number of participants with grade 3 or grade 4 for each type of toxicity encountered, using all toxicity evaluable patients.

Time frame: Up to 1 year

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityDyspnea (shortness of breath)5 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityLymphopenia4 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityHypoxia2 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicitySyncope (fainting)1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 Toxicitypulmonary/upper respiratory- other, acute respiratory event1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityThrombosis/thrombus/embolism1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityEncephalopathy1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityPericardial effusion1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityPain - Chest wall1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityAscites (non-malignant)1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicityEdema: trunk/genital1 Participants
Treatment (Nintedanib)Incidence of Grade 3-4 ToxicitySupraventricular and nodal arrhythmia - Atrial fibrillation1 Participants
Secondary

Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)

number of participants responded (complete response, partial response, stable disease, progressive disease, not evaluable) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)

Time frame: Up to 1 year

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
Treatment (Nintedanib)Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)complete response0 Participants
Treatment (Nintedanib)Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)partial response0 Participants
Treatment (Nintedanib)Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)stable disease0 Participants
Treatment (Nintedanib)Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)progressive disease18 Participants
Treatment (Nintedanib)Number of Participants Responded (Complete Response, Partial Response, Stable Disease, Progressive Disease, Not Evaluable)not evaluable2 Participants
Secondary

Overall Survival

Overall survival will be estimated using standard Kaplan-Meier methods for censored data, from which the median and other statistics of interest will be calculated (e.g., rates at 3 months, 6 months, 12 months).

Time frame: Up to 1 year

ArmMeasureValue (MEDIAN)
Treatment (Nintedanib)Overall Survival4.1 months

Source: ClinicalTrials.gov · Data processed: Feb 21, 2026