Study of Nintedanib and Chemotherapy for Advanced Pancreatic Cancer

NCT02902484 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: STU 022016-083
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The study will perform a clinical study evaluating the safety and tolerability of nintedanib when combined with standard chemotherapy (Gemcitabine + nab-Paclitaxel) for metastatic pancreatic cancer. It will utilize advanced imaging correlates including dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) which correlates with tumor grade and microvessel density.

Conditions

Cancer of Pancreas

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  A standard 3+3 phase 1 trial design will be used for Nintedanib monotherapy for a two week period (Days 1-14) followed by combination therapy of nintedanib plus chemotherapy. Two dose levels of nintedanib will be explored 150 mg BID and 200 mg BID. The combination phase will include gemcitabine + nab-paclitaxel, and nintedanib. Treatment will be administered intravenously on days 1, 8, 15 every 28 days. One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150 mg PO BID and 200mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days MTD assessed after combination therapy.

  Each 28 day cycle for up to 2 years

Study Arms (1)

Nintedanib Monotherapy

EXPERIMENTAL

One cycle of Nintedanib monotherapy followed by a total of eight cycles of both Nintedanib and the chemotherapeutic agents, or until disease progression, whichever comes first. 1. Nintedanib dose escalation: 150, 200 mg PO BID 2. Nab-paclitaxel: 125 mg/m2 day 1,8,15 every 28 days 3. Gemcitabine: 1000 mg /m2 day 1,8,15 every 28 days

Drug: Nintedanib

Interventions

Nintedanib DRUG

Nintedanib Monotherapy Followed by Combination Therapy of Nintedanib and Gemcitabine Plus nab-Paclitaxel

Also known as: Ofev, Vargatef

Nintedanib Monotherapy

Eligibility Criteria

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

You may qualify if:

• Signed and dated written informed consent prior to admission to the study;
• Histologically or cytologically confirmed metastatic or locally advanced adenocarcinoma of the pancreas;
• At least one measurable disease lesion according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1);
• Age ≥ 18 years;
• No more than one prior line of non-gemcitabine/nab-paclitaxel containing systemic therapy for metastatic/locally advanced pancreatic cancer;
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1;
• Women of childbearing potential must have a negative pregnancy test (urine or serum) within 14 days prior to registration; (Note: contraception in patients with reproductive capacity will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.)
• Adequate biological parameters at baseline (obtained within 14 days prior to registration).

You may not qualify if:

• More than one systemic therapy regimen of any type for metastatic or locally advanced disease. Adjuvant gemcitabine that ended more than 6 months from diagnosis of recurrent disease is not considered as a regimen;
• Prior treatment with nintedanib or any other VEGFR inhibitor;
• Known hypersensitivity to nintedanib, gemcitabine and nab-Paclitaxal peanut or soya or any other trial drug, their excipients or to contrast media;
• Chemo-, hormon-, radio-(except for brain and extremities) or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 4 weeks prior to treatment with the trial drug;
• Radiotherapy to the target lesion within the past 3 months prior to baseline imaging
• Persistence of clinically relevant therapy related toxicity from previous chemo and/or radiotherapy;
• 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);
• Leptomeningeal disease;
• Radiographic evidence of cavitary or necrotic tumors;
• Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial;
• Therapeutic anticoagulation with drugs requiring INR monitoring (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);
• Major injuries and/or surgery within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period;
• History of clinically significant hemorrhagic or thromboembolic event in the past 6 months;
• Known inherited predisposition to bleeding or thrombosis;
• 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);

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Boehringer Ingelheim: collaborator
• The University of Texas Health Science Center at San Antonio: collaborator
• South Plains Oncology Consortium: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75063, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

nintedanib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Salwan Al Mutar
• Organization: UT Southwestern Medical Center

salwan.almutar@utsouthwestern.edu

214-648-4008

Study Officials

• Salwan Al Mutar, MD

  UT Southwestern

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 2, 2016
• First Posted: September 15, 2016
• Study Start: September 7, 2017
• Primary Completion: October 26, 2021
• Study Completion: October 26, 2021
• Last Updated: June 3, 2024
• Results First Posted: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)