Neoplasms

All Conditions

Infections

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Communicable Diseases

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Papillomavirus Infections

Nasopharyngeal Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Crouzon Syndrome

Jackson-Weiss Syndrome

Pfeiffer Syndrome

Antineoplastic Agents

All Drugs and Chemicals

Infigratinib

Patients receive BGJ398 (125 mg) by mouth once daily on a three weeks on, one week off schedule. Courses repeat every 28 days until disease progression or unacceptable toxicity.

BGJ398

Tanguy Seiwert

This phase IIa trial studies how well the experimental drug, BGJ398 (infigratinib), works in treating patients with fibroblast growth factor receptor (FGFR) 1-3 translocated, mutated, or amplified head and neck cancer that has returned after a period of improvement. BGJ398 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

BGJ398 in Treating Patients With FGFR Positive Recurrent Head and Neck Cancer

Phase IIa Study of the Efficacy of Single Agent BGJ398 (Infigratinib) in FGFR1-3 Translocated, Mutated, or Amplified Squamous Cell Carcinoma of the Head and Neck

Novartis

University of Chicago

Patients receive BGJ398 (125 mg) by mouth once daily on a three weeks on, one week off schedule. Courses repeat every 28 days until disease progression or unacceptable toxicity.

BGJ398: Given by mouth (oral)

BGJ398 (Infigratinib) Dosing

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Study stopped enrollment due to poor accrual. Outcomes measures could not be analyzed due to lack of enrollment.

Technical Director

Study stopped after 1 patient enrolled. Endpoint could not be analyzed.

Objective Response Rate (Complete or Partial Response) Assessed by RECIST 1.1

Incidence of Adverse Events and Serious Adverse Events Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Overall Survival

Progression-free Survival

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Docetaxel

Tubulin Modulators

Antimitotic Agents

Participants receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, participants may be eligible to re-register to Arm III.

-closed to accrual 12/18/2015

Participants in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547

Laboratory Biomarker Analysis

Vassiliki Papadimitrakopoulou

This phase II/III trial studies how well FGFR inhibitor AZD4547 (AZD4547) works in treating patients with stage IV squamous cell lung cancer that has come back after previous treatment. This is a sub-study that includes all screened patients positive for the fibroblast growth factor receptor (FGFR) biomarker. FGFR can cause tumor cells to grow more quickly. AZD4547 may decrease the activity of FGFR and may be able to shrink tumors.

PRIMARY OBJECTIVES:

I. To evaluate if there is sufficient evidence to continue to the Phase III component by evaluating the objective response rate (ORR) with AZD4547 in FGFR-positive patients. (Phase II) II. If the study meets the criteria specified in S1400, the study will be amended to include a follow-on randomized Phase III trial. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate investigator-assessed progression free survival (IA-PFS) and overall survival (OS) in FGFR-positive patients treated with AZD4547. (Phase II) II. To evaluate the duration of response (DoR) among FGFR positive patients treated with AZD4547 who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II) III. To evaluate the frequency and severity of toxicities associated with AZD4547 in FGFR positive patients. (Phase II)

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To identify additional predictive tumor/blood biomarkers that may modify response or define resistance to the AZD4547 beyond the chosen biomarker for biomarker-driven sub-studies.

II. To identify potential resistance biomarkers at disease progression. III. To establish a tissue/ blood repository from patients with refractory squamous cell carcinoma (SCCA) of the lung.

OUTLINE: As of 12/18/2015, patients are assigned to Arm I.

ARM I: Patients receive FGFR inhibitor AZD4547 orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II (CLOSED TO ACCRUAL 12/18/2015): Patients receive docetaxel intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to Arm III.

ARM III: Patients in Arm II eligible for re-registration receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, all patients are followed up every 6 months for the first 2 years and then at the end of the year 3 from date of sub-study/re-registration.

Lung-MAP: AZD4547 as Second-Line Therapy in Treating FGFR Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer

A Phase II Study of AZD4547 for Previously Treated FGFR-Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study)

Will be monitored by the percentage of screened patients that register to a therapeutic sub-study.

Will be monitored by the percentage of patients that receive at least one dose of the treatment they are randomized to receive.

The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with AZD4547 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review, or symptomatic deterioration or death due to any cause among patients who achieve complete or partial response per RECIST v1.1.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of sub-study registration on study until death from any cause. Observations for participants last known to be alive were censored.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

Adverse Events (AEs) are reported per CTCAE Version 5.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.

It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment

National Cancer Institute (NCI)

SWOG Cancer Research Network

34 participants were assessed for AEs: 27 on AZD4547 and 9 on docetaxel arm. 2 participants that were re-registered from the docetaxel arm to receive AZD4547 after progression were assessed for AEs in both arms.

Adverse Events (AEs) are reported per CTCAE Version 5.0

Participants receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547: Given PO Laboratory Biomarker Analysis: Correlative studies

AZD4547

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, participants may be eligible to re-register to AZD4547.

Docetaxel: Given IV Other Names: Docecad Docetaxel RP56976 Taxotere Taxotere Injection Concentrate

Laboratory Biomarker Analysis: Correlative studies

Participants receive FGFR inhibitor AZD4547 PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

FGFR Inhibitor AZD4547: Given PO

Laboratory Biomarker Analysis: Correlative studies

Participants receive docetaxel IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Upon progression, patients may be eligible to re-register to AZD4547.

Docetaxel Given IV

Other Names:

* Docecad
* Docetaxel
* RP56976
* Taxotere
* Taxotere Injection Concentrate

Laboratory Biomarker Analysis: Correlative studies

Total

Age, Continuous

Black

White

Hispanic

Race/Ethnicity, Customized

Participants were graded according to the Zubrod Performance Status Scale.

0 - Fully active, able to carry out on all pre-disease performance without restriction.

1. - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g. light housework, office work.
2. - Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.

Performance status

Docetaxel arm closed before data were collected

Number of prior lines of therapy for stage IV disease

Smoking status

Lung Committee Statistician

Arm I - AZD4547

Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial)

Eligible and evaluable participants that achieved complete response or partial response.

Duration of Response Among Patients Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1

Dyspnea

Fatigue

Febrile neutropenia

Hyponatremia

Lung infection

Lymphocyte count decreased

Mucositis oral

Neutrophil count decreased

Retinopathy

Sepsis

White blood cell decreased

Participants who received at least one dose of AZD4547 treatment.

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs

Screen Success Rate

Treatment Arm Randomization Acceptance Rate

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Patients receive pemigatinib PO QD on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

Pemigatinib

Quality-of-Life Assessment

Kristen K Ciombor

This phase II trial studies how well pemigatinib works in treating patients with colorectal cancer with mutations (alterations) in a FGFR gene and that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Pemigatinib may stop the growth of tumor cells by blocking FGFR, which is needed for cell growth.

PRIMARY OBJECTIVE:

I. To assess overall response rate (ORR) of pemigatinib in patients with metastatic or unresectable colorectal cancer harboring activating FGFR alterations.

SECONDARY OBJECTIVES:

I. To assess the clinical benefit rate (complete response + partial response + stable disease) with pemigatinib.

II. To assess progression free survival (PFS) and overall survival (OS) with pemigatinib.

III. Assess changes in patient quality of life (QOL) as measured by the linear analogue self-assessment (LASA) questionnaire.

IV. Assess the frequency and severity of adverse events.

CORRELATIVE RESEARCH OBJECTIVES:

I. To assess plasma pharmacodynamic biomarkers of response and resistance to therapy.

II. To explore any correlation between tissue and blood based biomarkers and clinical outcomes.

OUTLINE:

Patients receive pemigatinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.

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

Pemigatinib for the Treatment of Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations

A Phase II, Multicenter, Single-Arm Study of Pemigatinib in Patients With Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations

Defined as the rate of patients, among evaluable patients, who experience an objective response per RECIST 1.1. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Clinical Benefit Rate is defined as the number of patients that experience a complete or partial response, or have stable disease, divided by the number of evaluable patients. Analysis of this endpoint will mirror that of the primary objective.

Progression-free survival (PFS) is defined as the time from study entry to the first of either disease progression or death from any cause, where disease progression is determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and corresponding 95% confidence interval will be reported. Patients who do not experience disease progression or death while on protocol will be censored at the last disease assessment date.

Overall survival (OS) is defined as the time from study entry to death from any cause. Will be estimated using the Kaplan-Meier method. The median OS and corresponding 95% confidence interval will be reported.

Quality of Life (QOL) was measured using item 1: Overall QOL of the Linear Analogue Self-Assessment (LASA) Questionnaire on a 0-10 scale, with 0=as bad as it can be and 10=as good as it can be. The QOL scores was converted to a 100-point scale, with 0=Low QOL and 100=Best QOL. Change from baseline to Week 36 will be calculated by subtracting the baseline scores from the scores at Week 36. Negative change indicates the QOL decrease and positive change indicates the QOL improvement.

Adverse events will be summarized by frequency and severity using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 in the adverse event section of this report. The number of patients evaluated for adverse events is reported below.

Academic and Community Cancer Research United

Treatment (Pemigatinib)

Tanios Bekaii-Saab M.D.

Overall Response Rate (ORR)

Clinical Benefit Rate

Progression-free Survival (PFS)

Overall Survival (OS)

All patients that completed and submitted the baseline and week 36 Linear Analogue Self-Assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BGJ398 in Treating Patients With FGFR Positive Recurrent Head and Neck Cancer	NCT02706691	FGFR Gene Ampli... FGFR1 Gene Ampl... FGFR2 Gene Ampl... FGFR2 Gene Muta... FGFR3 Gene Muta... Head and Neck S... Human Papilloma... Recurrent Head ... Recurrent Nasop... Recurrent Oroph...	BGJ398	18 Years -	University of Chicago
Lung-MAP: AZD4547 as Second-Line Therapy in Treating FGFR Positive Patients With Recurrent Stage IV Squamous Cell Lung Cancer	NCT02965378	FGFR1 Gene Ampl... FGFR1 Gene Muta... FGFR2 Gene Ampl... FGFR2 Gene Muta... FGFR3 Gene Ampl... FGFR3 Gene Muta... Recurrent Squam... Stage IV Squamo...	Docetaxel FGFR Inhibitor ... Laboratory Biom...	25 Years -	SWOG Cancer Research Network
Pemigatinib for the Treatment of Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations	NCT04096417	FGFR1 Gene Ampl... FGFR1 Gene Muta... FGFR1 Gene Tran... FGFR2 Gene Ampl... FGFR2 Gene Muta... FGFR2 Gene Tran... FGFR3 Gene Ampl... FGFR3 Gene Muta... FGFR3 Gene Tran... Metastatic Colo... Stage III Color... Stage IIIA Colo... Stage IIIB Colo... Stage IIIC Colo... Stage IV Colore... Stage IVA Color... Stage IVB Color... Stage IVC Color... Unresectable Co...	Pemigatinib Quality-of-Life...	18 Years -	Academic and Community Cancer Research United

Spots Global Cancer Trial Database for fgfr2 gene amplification