Afatinib Dimaleate and Capecitabine in Treating Patients With Advanced Refractory Solid Tumors, Pancreatic Cancer or Biliary Cancer

NCT02451553 | Completed Phase 1 DMC

• 3 other identifiers: 9078NCI-2015-00684RG1715055
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/Ib trial studies the side effects and best dose of afatinib dimaleate when given together with capecitabine in treating patients with solid tumors, pancreatic cancer, or biliary cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment and has not responded to previous treatment. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving afatinib dimaleate together with capecitabine may be a better treatment for solid tumors, pancreatic cancer, or biliary cancer.

Conditions

Advanced Malignant Solid Neoplasm; Bile Duct Carcinoma; Recurrent Malignant Solid Neoplasm; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer AJCC v6 and v7; Stage IVA Pancreatic Cancer; Stage IVB Pancreatic Cancer

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events, assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  Adverse events will be tabulated and summarized by dose levels. Summary tabulations will be presented displaying the number of observations, mean, standard deviation, median, minimum, and maximum for continuous variables, and the number and percentage per category for categorical data. Toxicity measurement will be accompanied by 90% confidence intervals.

  Up to 30 days following the last dose of study treatment

• Incidence of dose limiting toxicity (DLT) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase Ib)

  DLTs will be tabulated and summarized by dose levels. Summary tabulations will be presented displaying the number of observations, mean, standard deviation, median, minimum, and maximum for continuous variables, and the number and percentage per category for categorical data. Toxicity measurement will be accompanied by 90% confidence intervals.

  Up to 21 days

• Maximum tolerated dose (MTD) of afatinib dimaleate in combination with capecitabine (Phase Ib)

  Defined as the dose at which 0/3 or =\< 1/6 patients experience a DLT graded according to NCI CTCAE version 4.0, will be assessed.

  Up to 21 days

• Recommended phase 2 dose (RP2D) (Phase Ib)

  Defined as the best tolerated dose overall, considering overall toxicity, including beyond course 1, will be evaluated.

  Up to 3 years

Secondary Outcomes (8)

• Biomarker profile (including EGFR and HER2 gene copy number and mutations, Kirsten rat sarcoma viral oncogene homolog, B-Raf proto-oncogene, serine/threonine kinase, neuroblastoma RAS viral oncogene homolog NRAS mutations, and E-cadherin expression)

  Baseline

• Duration of response

  Time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years

• Duration of stable disease

  Time that stable disease is documented until the first date that recurrent disease is objectively documented, assessed up to 3 years

• Overall survival

  From the day of first treatment to the earlier of (1) death (from any cause) and (2) the last date of subject contact, assessed up to 3 years

• Progression-free survival

  From time from registration to disease progression or death of any cause, assessed up to 3 years

Study Arms (1)

Treatment (afatinib dimaleate, capecitabine)

EXPERIMENTAL

Patients receive afatinib dimaleate PO QD on days 1-21 and capecitabine PO BID on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: Afatinib Dimaleate; Drug: Capecitabine; Other: Laboratory Biomarker Analysis

Interventions

Afatinib Dimaleate DRUG

Given PO

Also known as: (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate), BIBW 2992MA2, BIBW2992 MA2, Gilotrif

Treatment (afatinib dimaleate, capecitabine)

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Treatment (afatinib dimaleate, capecitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (afatinib dimaleate, capecitabine)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE I:
• PHASE I: Histologically confirmed solid tumor malignancy
• PHASE I: Life expectancy \>= 12 weeks
• PHASE I: No limit on the number of prior systemic therapies for metastatic disease
• PHASE I: Prior treatment with erlotinib, gefitinib or EGFR-blocking monoclonal antibodies (cetuximab and panitumumab) is allowed
• PHASE I: Signed informed consent
• PHASE I: Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
• PHASE I: Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• PHASE I: Must be willing to provide tumor tissue biopsy samples (may be fresh or archival paraffin embedded) at baseline
• PHASE I: In order to perform a retrospective biomarker analysis with the next generation gene sequencing UW-OncoPlex assay; fresh tumor biopsies from metastatic or primary tumor lesion will be done if considered safe and feasible by treating physician and radiologist; Patients who already have OncoPlex or other equivalent gene sequencing assay (eg Foundation One, Perthera, Caris etc) test results available from prior tumor biopsy are eligible to participate, without the needed of a repeat tumor biopsy, but the test results need to be provided to the study principal investigator
• PHASE I: Females of childbearing potential must use an effective method of contraception (barrier method of birth control or abstinence) from the time of consent until at least 180 days following discontinuation of protocol therapy; females of childbearing potential must have a negative pregnancy test within 3 days prior to registration for protocol therapy; patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months; females must not be pregnant or breastfeeding; in rare cases of an endocrine-secreting tumor, human chorionic gonadotropin (hCG) levels may be above normal limits (falsely-positive) but with no pregnancy in the patient; in these cases, there should be a repeat serum hCG test (with a non-rising result) to rule out pregnancy; upon confirmation of results and discussion with the Sponsor-Investigator, these patients may enter the study
• PHASE I: Sexually active male subjects must use an effective method of contraception (barrier method of birth control or abstinence) from the time of consent until at least 180 days following discontinuation of protocol therapy
• PHASE I: Absolute neutrophil count \>= 1500/uL
• PHASE I: Platelet count \>= 100,000/uL
• PHASE I: Hemoglobin \>= 9 gm/dL

You may not qualify if:

• Prior treatment with afatinib
• Untreated or symptomatic brain metastases requiring corticosteroid therapy (no corticosteroid use for this purpose in the preceding 4 weeks)
• Diagnosis with any of the following in the 12 months prior to registration: severe/unstable angina, myocardial infarction, uncontrolled cardiac arrhythmia, congestive heart failure, cerebrovascular accident or transient ischemic attack
• Active venous thrombosis with contraindication for anticoagulation
• Patients taking warfarin; if anticoagulation is required, the patient must be on a stable dose of a Food and Drug Administration (FDA) approved anticoagulant other than warfarin (e.g. enoxaparin, dalteparin, fondaparinux, apixaban, rivaroxaban) for at least 30 days
• Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient?s ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
• Gastrointestinal tract disease or any other reasons resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, active peptic ulcer disease or chronic diarrhea
• History of bone marrow transplant and stem cell rescue
• Receipt of any chemotherapy, biological therapy or investigational agents within 3 weeks prior to study registration
• Radiotherapy within 4 weeks prior to therapy except palliative radiation to target organs other than primary tumor may be allowed up to 2 weeks prior to registration
• Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
• Known pre-existing interstitial lung disease
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn?s disease, ulcerative colitis, chronic diarrhea, malabsorption)
• Known active hepatitis B infection (defined as presence of hepatitis B \[HepB\] surface antigen \[sAg\] and/or Hep B deoxyribonucleic acid \[DNA\]), known active hepatitis C infection (defined as presence of hepatitis C \[Hep C\] ribonucleic acid \[RNA\]) and/or known human immunodeficiency virus (HIV) carrier

Sponsors & Collaborators

• University of Washington: lead

Study Sites (2)

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Bile Duct Neoplasms; Pancreatic Neoplasms

Interventions

Afatinib; Capecitabine

Condition Hierarchy (Ancestors)

Biliary Tract Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Elena G. Chiorean

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: May 22, 2015
• Study Start: November 5, 2015
• Primary Completion: April 16, 2022
• Study Completion: April 16, 2022
• Last Updated: June 7, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)