Study with investigational drug PF-06463922 in patients with a specific type of advanced lung cancer

• Register: EUCTR
• Last refreshed on: 23 October 2023
• Main ID: EUCTR2013-002620-17-ES
• Date of registration: 05/12/2013
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: Study with investigational drug PF-06463922 in patients with a specific type of advanced lung cancer
• Scientific title: Phase 1/2 study of PF-06463922 (an ALK/ROS1 tyrosine kinase inhibitor) in patients with advanced non-small cell lung cancer harboring specific molecular alterations.
• Date of first enrolment: 21/03/2014
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002620-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Poland, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC (Stage IV, AJCC v7.0) that carries an ALK rearrangement, as determined by the Food and Drug Administration (FDA)-approved FISH assay (Abbott Molecular Inc) or by Immunohistochemistry (IHC) (Ventana Inc), or a ROS1 rearrangement as determined by FISH or RT-PCR or Next Generation Sequencing (NGS) via a local diagnostic test (LDT). A central laboratory confirmation by a Sponsor-selected, validated test will retrospectively determine final ROS1 status. All patients (ALK positive and ROS1 positive) must have archival tissue sample available and collected prior to enrollment.
2. ALK+ NSCLC patients must either be treatment naïve in the advanced setting or have had disease progression after 1 or 2 previous ALK inhibitor therapy(ies), as the last therapy given. ROS1+ NSCLC patients must either be treatment naïve in the advanced setting or have had disease progression after 1 or 2 previous ROS1 inhibitor therapy(ies), as the last therapy given.
3. Tumor Requirements:
Phase 1: All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients asymptomatic by means of stable or decreasing doses of steroids within the last 2 weeks prior to study entry) will be eligible. The brain metastases may be newly diagnosed or be present as progressive disease after surgery, whole brain radiotherapy or stereotactic radiosurgery (see Exclusion Criterion #3 for the lapsed time period required between the end of radiotherapy and study entry). Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) are not eligible to entry in the Phase 1.
Phase 2: All Patients must have at least one measurable target extracranial lesion according to RECIST v1.1. In addition patients with asymptomatic CNS metastases (including patients controlled with stable or decreasing steroid use within the last 2 weeks prior to study entry) will be eligible. The brain metastases may be newly diagnosed or be present as progressive disease after surgery, whole brain radiotherapy or stereotactic radiosurgery (see Exclusion Criterion #3 for the lapsed time period required between the end of radiotherapy and study entry). Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) will be eligible if the LM/CM is visualized on MRI or if documented baseline cerebral spinal fluid (CSF) positive cytology is available.
4. Age ?18 years.
5. ECOG Performance Status (PS):
- Phase 1: 0 or 1;
- Phase 2: 0, 1, or 2.
6. Adequate Bone Marrow Function, including:
- Absolute Neutrophil Count (ANC) ?1.5 x 109/L;
- Platelets ?100 x 109/L;
- Hemoglobin ?9 g/dL.
7. Adequate Pancreatic Function, including:
- Serum amylase (pancreatic isoenzyme) ?1.5 upper limit of normal (ULN);
- Serum lipase ?1.5 ULN.
8. Adequate Renal Function, including:
- Serum creatinine ?1.5 x ULN or estimated creatinine clearance ?60 mL/min as calculated using the method standard for the institution.
9. Adequate Liver Function, including:
- Total serum bilirubin ?1.5 x ULN;
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ?2.5 x ULN; ?5.0 x ULN if there is liver metastases involvement;
- Alkaline phosphatase ?2.5 x ULN (?5 x ULN in case of bone metastasis).
10. Acute effects of any prior therapy resolved to baseline severity or to CTCAE Grade ?1 except for AEs that in
Exclusion criteria:
1.Spinal cord compression is excluded unless the patient demonstrates good pain control attained through therapy and there is stabilization or recovery of neurological function for the 4 weeks prior to study entry
2.Major surgery within 4 weeks of study entry.Minor surgical procedures are not excluded but sufficient time should have passed for wound healing
3.Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry.Palliative radiation (?10 fractions) must have been completed at least 48 hours prior to study entry.Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry.Whole brain radiation must have completed at least 4 weeks prior to study entry
4.Systemic anti-cancer therapy completed within 2 weeks or 5 half-lives of study entry
5.Previous high-dose chemotherapy requiring stem cell rescue
6.Prior irradiation to >25% of the bone marrow
7.Active and clinically significant bacterial, fungal, or viral infection including HBV, HCV, known HIV or AIDS-related illness
8.Any one of the following currently or in the previous 3 months: myocardial infarction,congenital long QT syndrome,Torsades de Pointes,arrhythmias,right bundle branch block and left anterior hemiblock (bifascicular block),unstable angina,coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident,transient ischemic attack or symptomatic pulmonary embolism not adequately medically managed with anticoagulants;as well as bradycardia defined as <50 bpms.Ongoing cardiac dysrhythmias of NCI CTCAE Grade ?2,symptomatic atrial fibrillation of any grade,or QTc interval ?481 msec at screening.Right bundle branch block
9.Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (see protocol for more details).
10.History of extensive,disseminated,bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersentivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis. Patients with history of prior radiation pneumonitis are not excluded
11.Participation in other studies within 2 weeks prior to study entry
12.Other severe acute or chronic medical or psychiatric condition,including recent (within the past year) or active suicidal ideation or behavior,or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and,in the judgment of the investigator,would make the patient inappropriate for entry into this study
13.Patients who are investigational site staff members directly involved in the conduct of the trial and their family members,site staff members otherwise supervised by the Investigator,or patients who are Pfizer employees directly involved in the conduct of the trial
14.Evidence of active malignancy within the last 3 years. See protocol for more details
15.Active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease or previous gastric resection or lap band. Gastroesophageal reflux disease under treatment with proton-pump inhibitors is allowed

For more exclusion criteria refer to the protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Anaplastic Lymphoma Kinase (ALK)-positive (ALK+) or ROS oncogene 1 (ROS1)-positive (ROS1+) advanced non-small cell lung cancer (NSCLC).
MedDRA version: 14.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: PF-06463922
Product Code: PF-06463922
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06463922
Other descriptive name: PF-06463922 Form 3 (acetic acid solvate)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: PF-06463922
Product Code: PF-06463922
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06463922
Other descriptive name: PF-06463922 Form 3 (acetic acid solvate)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: PF-06463922
Product Code: PF-06463922
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06463922
Other descriptive name: PF-06463922 Form 3 (acetic acid solvate)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: Please refer to study protocol to ckeck separate secondary objectives for the two study portions Phase 1 and Phase 2.

Primary end point(s): Phase 1 Primary Endpoint:
- Cycle 1 Dose-Limiting Toxicities (DLTs).
Phase 2 Primary Endpoint:
- Objective tumor response, as assessed by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. In patients with asymptomatic CNS metastases, up to five (5) intracranial target lesions in addition to the five (5) extracranial target lesions will be assessed.

Timepoint(s) of evaluation of this end point: Phase 1 Primary Endpoint:
- Cycle 1 Dose-Limiting Toxicities (DLTs): cycle 1.
Phase 2 Primary Endpoint:
- Objective tumor response: at baseline and at the stipulated intervals during treatment.
Please refer to Schedule of Activities of the protocol.

Main Objective: This study has separate primary objectives for the two study portions: Phase 1 and Phase 2.
Phase 1 study portion:
To assess safety and tolerability of PF-06463922 as a single agent at increasing dose levels in patients with advanced ALK+ or advanced ROS1+ NSCLC in order to estimate the Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D).
Phase 2 study portion:
To evaluate overall (intra- and extra-cranial) and intracranial anti-tumor activity of single-agent PF-06463922 at RP2D in patients with advanced ALK+ NSCLC and advanced ROS1+ NSCLC.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to Schedule of Activities of the protocol.

Secondary end point(s): Secondary Endpoints [all patients unless otherwise indicated]:
- MTD and RP2D [Phase 1 only].
- Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE v.4.03), timing, seriousness and relationship to study therapy.
- Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v.4.03) and timing.
- Vital Signs (heart rate, blood pressure).
- Total Mini Mental State Examination Score.
- Pharmacokinetic parameters of PF-06463922: Single Dose - Cmax, Tmax, AUClast,AUC t, CL/F, and Vz/F and t1/2, AUCinf as data permit. Multiple Dose (assuming steady-state is achieved) - Css,max, Tss,max, AUCss,t, t1/2, Css,min, Css,av, CL/F, Vss/F, Rac (AUCss,t/AUCsd,t) and Rss (AUCss,t/AUCsd,inf) as data permit. Urine PK parameters (Ae%, and CLR) of PF-06463922 from MDZ and food effect substudy.
- Pharmacokinetic parameters of midazolam: Cmax, Tmax, AUClast, CL/F, and Vz/F and t1/2, AUCinf as data permit.
- Patient reported functioning and impact on disease/treatment-related symptoms of lung cancer and global QOL.
- QTc interval.
- Time-to-event endpoints: eg, Duration of Response (DR), Progression-Free Survival (PFS), Overall Survival (OS).
- CTC enumeration and molecular characterization.
- Selected molecular profiling of tumor tissue, eg, ALK kinase domain mutations.
- Selected molecular profiling of Circulating Nucleic Acid (CNA), eg, ALK kinase domain mutations.
- CSF concentration of PF-06463922.

Secondary ID(s)

B7461001

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date: 24/01/2014
Contact:

Results

• Results available: Yes
• Date Posted: 24/03/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-002620-17/results