Trial of Afatinib in Combination With Weekly Paclitaxel in the Second Line Treatment

NCT02274012 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: AAAM59051200.203
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators are doing this research program to find out if the investigational drug, afatinib which is a medication known to block the function of the ErbB2 protein might help standard chemotherapy, in particular paclitaxel, work better. Afatinib (GILOTRIF) is a highly potent, irreversible inhibitor of the EGFR and HER2. On July 12, 2013 the United States Food and Drug Administration (US FDA) approved afatinib for the first-line treatment of patients with metastatic non-small cell lung cancer whose tumors had specific EGFR gene mutations (exon 19 deletions or exon 21 i.e. L858R substitution mutations) as detected by an FDA approved test. Paclitaxel is a standard, anti-cancer medicine that has been approved by the US Food and Drug Administration (FDA) for the treatment of lung cancer. The combination of Afatinib and Paclitaxel are considered investigational when used in this research program. An investigational drug is a drug that is not approved by the FDA for its indication.

Conditions

HER-2 Positive Gastric Cancer; Gastrooesophageal Cancer; Esophageal Cancer

Keywords

Gastric; Gastroesophageal Junction; Gastroesophageal Cancer; Esophageal Cancer; Metastatic; HER2 amplified; Afatinib

Outcome Measures

Primary Outcomes (1)

• Change of tumor burden (in centimeters) for participants during protocol therapy

  Change from Baseline Tumor burden, measured every 8 weeks, up to approximately 4 years

Secondary Outcomes (5)

• Number of participants with adverse events.

  up to approximately 36 months

• Total number of circulating tumor cell (CTC) numbers.

  up to approximately 36 months

• Clinical benefit in progression free survival.

  every 3 months up to approximately 4 years

• Clinical benefit in overall survival.

  every 3 months up to approximately 4 years

• ErbB2 levels benefit during therapy.

  up to approximately 4 years

Study Arms (1)

Afatinib and weekly Paclitaxel

EXPERIMENTAL

In addition to the standard chemotherapy, afatinib 40 mg orally once daily will be administered starting on the first day of paclitaxel. Translational studies to assess circulating tumor cells at the start of therapy and then at several later time points, including at the time of progression. These studies will assess the correlation of circulating tumor cell numbers with radiographic response and pilot studies will also be conducted to assess HER2 expression, HER2 genomic amplification, HER2 pathway activation and secondary genetic changes in the HER2 coding sequence as well as other pathway components.

Drug: Afatinib; Drug: Paclitaxel

Interventions

Afatinib DRUG

Afatinib 40mg/PO daily will be administered in combination to standard of care paclitaxel.

Also known as: BIBW 2992

Afatinib and weekly Paclitaxel

Paclitaxel DRUG

On the day of the first dose of afatinib, paclitaxel will be administered at a dose of 80 mg/m2 intravenously over 60 minutes on days 1, 8 and 15 of a 28-day cycle.

Also known as: Taxol

Afatinib and weekly Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the intrathoracic esophagus, gastrointestinal junction or stomach.
• Tumor must be HER2 positive 3+ by immunohistochemistry or positive by Fluorescence in situ hybridization (FISH) analysis if 2+ by immunohistochemistry.
• Received and failed at least one prior cytotoxic chemotherapy regimen for advanced disease that included trastuzumab.
• Age greater than or equal to 18 years.
• At least one measurable lesion as defined by modified RECIST criteria.
• ECOG performance status less than or equal to 2.
• Life expectancy of at least 12 weeks.
• Normal organ and marrow function as defined.
• Able to swallow and retain oral medication.
• Left ventricular ejection fraction (LVEF) within institutional range of normal as measured by echocardiogram (ECHO).
• Prior malignancy is acceptable if the subject is considered to be cured.
• Ability to understand and the willingness to sign a written informed consent document.
• All subjects of childbearing potential must agree to use acceptable methods of birth control (Men and Women).
• Willingness to consent to the use of baseline diagnostic tumor specimen for correlative studies.

You may not qualify if:

• Squamous cell carcinoma.
• History of clinically relevant cardiovascular abnormalities within 6 months.
• Baseline (less than 1 month before treatment) cardiac left ventricular function with resting ejection fraction of less than 50 percent measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram.
• Pregnant and lactating women are excluded from the study.
• Significant or recent acute gastrointestinal disorders with diarrhea.
• More than 2 prior cytotoxic chemotherapy regimens for relapsed or metastatic disease.
• Major surgery, chemotherapy, radiation therapy or other cancer therapy within 3 weeks of treatment day 1.
• Use of any investigational drug within 4 weeks.
• Prior treatment with taxanes if given as full-dose chemotherapy for advanced disease.
• Prior treatment with afatinib or any other HER2 inhibitor other than trastuzumab.
• Front-line chemotherapy that did not contain trastuzumab.
• Active central nervous system disease (CNS) metastases.
• Planned concurrent anti-cancer therapy while taking investigational treatment.
• Unresolved or unstable, serious toxicity from prior cancer treatment (any toxicities greater than grade 2).
• Peripheral neuropathy of Grade 2 or greater

Sponsors & Collaborators

• Columbia University: lead
• Boehringer Ingelheim: collaborator

Related Links

• Herbert Irving Comprehensive Cancer Center (HICCC) Clinical Trials Page

MeSH Terms

Conditions

Esophageal Neoplasms; Neoplasm Metastasis

Interventions

Afatinib; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Naiyer Rizvi, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 15, 2014
• First Posted: October 24, 2014
• Study Start: May 29, 2014
• Primary Completion: August 12, 2015
• Study Completion: August 12, 2015
• Last Updated: March 14, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share