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Advanced Malignant Solid NeoplasmPhase 1NCT02451553

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

A Phase 1 study testing Afatinib Dimaleate, Capecitabine and Laboratory Biomarker Analysis in people with Advanced Malignant Solid Neoplasm and Bile Duct Carcinoma, run by University of Washington at 2 sites in United States.

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 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… Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Afatinib Dimaleate, Capecitabine and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
2 sitesUnited States
Study dates
5 Nov 2015to 16 Apr 2022
Phase
Phase 1
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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 40Show fewer
  • 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
  • PHASE I: Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • PHASE I: Transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) =< 2.5 x ULN
  • PHASE I: Prothrombin time (PT) (or international normalized ratio [INR]) and partial thromboplastin time (PTT) =< 1.5 x ULN
  • PHASE I: Calculated creatinine clearance (CrCl) >= 60 mL/min calculated by Cockcroft-Gault formula
  • PHASE IB:
  • PHASE IB: Histologically confirmed refractory locally-advanced unresectable or metastatic pancreatic or biliary cancer
  • PHASE IB: Life expectancy >= 12 weeks
  • PHASE IB: =< 2 lines of prior systemic therapy for metastatic disease (if patients have metastatic disease)
  • PHASE IB: =< 2 lines of prior systemic therapy for patients with progressive locally-advanced disease
  • PHASE IB: No prior treatment with erlotinib is allowed for pancreatic cancer patients
  • PHASE IB: ECOG PS 0-1
  • PHASE IB: Signed informed consent
  • PHASE IB: Measurable disease according to RECIST v1.1
  • PHASE IB: Must be willing to provide tumor tissue biopsy samples (may be fresh or archival paraffin embedded) at baseline
  • PHASE IB: Fresh tumor biopsies from metastatic or primary tumor lesions will be done only 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 available to the study principal investigator
  • PHASE IB: 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, 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 IB: 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 IB: Patients in the expansion cohort must have a measurable site of disease according to RECIST (v 1.1) that has not been previously irradiated, or evidence of at least 20% progression in a previously irradiated lesion, and assessed by imaging within 28 days prior to registration for protocol therapy
  • PHASE IB: Absolute neutrophil count >= 1500/uL
  • PHASE IB: Platelet count >= 100,000/uL
  • PHASE IB: Hemoglobin >= 9 gm/dL
  • PHASE IB: Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • PHASE IB: Transaminases (AST and/or ALT) =< 2.5 x ULN
  • PHASE IB: PT (or INR) and PTT =< 1.5 x ULN
  • PHASE IB: Calculated creatinine clearance (CrCl) >= 60 mL/min calculated by Cockcroft-Gault formula

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Phase I/IB Multi-center Study of Irreversible EGFR/HER2 Tyrosine Kinase Inhibitor Afatinib (BIBW 2992) in Combination With Capecitabine for Advanced Solid Tumors and Pancretico-Biliary Cancers

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety, maximum tolerated dose (MTD), and the recommended phase II dose (RP2D) of afatinib dimaleate (afatinib) in combination with capecitabine in patients with advanced solid tumors (phase I) and pancreatico-biliary cancers (phase Ib). (Phase I/Ib)

SECONDARY OBJECTIVES:

  1. Evaluate biomarkers of response from tumor biopsies, including markers related to the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) pathways via OncoPlex or other equivalent gene sequencing assay. (Phase I/Ib)

II. Evaluate rates of response and stable disease, duration of response, time to progression, progression-free and overall survival. (Phase I/Ib)

OUTLINE: This is a phase I, dose-escalation study of afatinib dimaleate followed by a phase Ib study.

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

After completion of study treatment, patients are followed up every 3 months for 3 years.

Being tested
Afatinib Dimaleate, Capecitabine, Laboratory Biomarker Analysis
Medical subject headings
Bile Duct Neoplasms, Pancreatic Neoplasms

What participants receive

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

  • Afatinib DimaleateDrug

    Also called (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

    Given PO

  • CapecitabineDrug

    Also called Ro 09-1978/000, Xeloda

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02451553
Study groupRoleWhat they receive
Treatment (afatinib dimaleate, capecitabine)ExperimentalPatients 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.
Receives: Drug: Afatinib Dimaleate; Drug: Capecitabine; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. 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.

    Measured: Up to 30 days following the last dose of study treatment

  2. 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.

    Measured: Up to 21 days

  3. 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.

    Measured: Up to 21 days

  4. Recommended phase 2 dose (RP2D) (Phase Ib)

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

    Measured: Up to 3 years

Secondary outcomes (8)

  1. 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)

    Will be summarized using mean +/- standard deviation. Baseline biomarker profile will also be summarized by the categories of treatment responses. Logistic models with objective response and stable disease as outcome and the baseline tumor profile as covariate will be fitted to evaluate their association. Correlative analysis of the presence of specific biomarkers and objective response/stable disease and progression free survival (PFS) (for patients in expansion cohorts) will be performed using Chi-square test or Fisher?s exact tests, as appropriate.

    Measured: Baseline

  2. Duration of response

    Duration of response will be assessed with the Kaplan-Meier method.

    Measured: 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

  3. Duration of stable disease

    Duration of stable disease will be assessed with the Kaplan-Meier method.

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

  4. Overall survival

    Overall survival will be assessed with the Kaplan-Meier method.

    Measured: 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

  5. Progression-free survival

    Assessed with the Kaplan-Meier method.

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

  6. Rates of response, assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria

    Response rates will be tabulated and summarized by dose levels. Response rate measurement will be accompanied by 90% confidence intervals.

    Measured: Up to 3 years

  7. Stable disease, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to quality for progressive disease assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria

    Stable disease will be tabulated and summarized by dose levels.

    Measured: Up to 3 years

  8. Time to progression

    Time to progression will be assessed with the Kaplan-Meier method.

    Measured: From the study enrollment until the criteria for disease progression are met (or death occurs), assessed up to 3 years

Timeline

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

  1. First posted22 May 2015 (estimated)
  2. Study start5 Nov 2015
  3. Primary completion16 Apr 2022
  4. Study completion16 Apr 2022

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02451553
Sponsor's protocol ID
9078
Other IDs
NCI-2015-00684, 9078, RG1715055
Status last verified
Jun 2022
First submitted
19 May 2015
Last updated
7 Jun 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Afatinib Dimaleate, Capecitabine and Laboratory Biomarker Analysis in people with Advanced Malignant Solid Neoplasm and Bile Duct Carcinoma, run by University of Washington at 2 sites in United States.

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 40 inclusion and 14 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 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this 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.

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?

Incidence of adverse events, assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: Up to 30 days following the last dose of study treatment). The study lists 4 primary outcomes in all. 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 NCT02451553.

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 7 Jun 2022.

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