Phase 1/2 study evaluating the safety and anti-tumor activity of PD 0332991 in combination with Velcade and dexamethasone in patients with multiple myeloma

• Register: EUCTR
• Last refreshed on: 3 February 2014
• Main ID: EUCTR2010-022515-20-DE
• Date of registration: 29/11/2010
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017, USA
• Public title: Phase 1/2 study evaluating the safety and anti-tumor activity of PD 0332991 in combination with Velcade and dexamethasone in patients with multiple myeloma
• Scientific title: PHASE 1/2 OPEN-LABEL STUDY OF THE SAFETY AND EFFICACY OF PD 0332991 IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE IN PATIENTS WITH REFRACTORY MULTIPLE MYELOMA - n/a
• Date of first enrolment: 19/01/2011
• Target sample size: 47
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022515-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Czech Republic, Germany

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of symptomatic multiple myeloma as defined by International Myeloma
Working Group (IMWG).
2. Phase 1: Relapsed or relapsed/refractory myeloma after at least 1 previous treatment and with a life expectancy of more than 3 months. Phase 2: Measurable (as defined by IMWGURC) progressive disease after at least 1 previous treatment.
Chemotherapy/salvage chemotherapy followed by autologous stem cell rescue (single or tandem) will be considered as one prior therapy.
3. Patient’s tumors must express retinoblastoma (Rb), as assessed using an historical biopsy sample, if available, or a freshly obtained tumor sample. If = 90% of the patients screened for the Phase 1 part of this study are positive for Rb, then this will not be an inclusion criterion for the Phase 2 part of this study.
4. Men and women > 18 years old
5. ECOG performance status of 0 to 2.
6. Hematology: Hemoglobin = 8.0 g/dL, ANC =750/µL, and platelet count =75,000/µL.
7. Creatinine clearance = 30 ml/min.
8. AST or ALT = 3xULN (=5xULN for patients with liver involvement)
9. Total Bilirubin = 1.5xULN
10. QTc interval of = 470 msec.
11. All previous therapies for cancer, including radiotherapy and investigational therapies discontinued for at least 4 weeks (2 weeks for lenalidomide or thalidomide) before study entry and all acute effects of any prior therapy are not considered to be clinically important.
12. Patients must give written informed consent.
13. Willingness and ability to comply with the study scheduled visits, treatment plans,
laboratory tests and other procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 26

Exclusion criteria:
1. History of allogeneic stem cell transplant.
2. Known malabsorption syndrome or other condition that may impair absorption of
study medication.
3. Phase 2 only: Prior PD 0332991 therapy or prior history of other advanced/metastatic malignancy (other than multiple myeloma). Prior bortezomib therapy will only be allowed if there was a demonstrated positive response (sCR, CR, VGPR or PR), and disease progression occurred off therapy.
4. Patients must not have experienced significant hematological toxicities, e.g. platelets = 30,000/µL, while on previous bortezomib therapy.
5. Uncontrolled infection, or current drug or alcohol abuse.
6. Prior radiation therapy to > 25% of the bone marrow (whole pelvis is 25%). [Note:
does not include palliative radiation.]
7. Peripheral neuropathy with Grade = 2 (CTCAE version 3.0)
8. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
9. Known human immunodeficiency virus (HIV) or acquired immunodeficiency
syndrome (AIDS)-related illness.
10. Concurrent therapy with other investigational or approved agents for malignancy
beyond the scope of this trial.
11. Concurrent administration of herbal preparations.
12. Patients with untreated brain metastases. If clinical evidence exists of brain
metastases in the screening period, brain metastases must be ruled out with a CT scan or MRI. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment at least 10 days prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 5 days, and are neurologically stable.
13. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, or in the judgment of the investigator would make the patient inappropriate for entry into the study.
14. Pregnancy or breast feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 21 days of starting treatment.


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

Health Condition(s) or Problem(s) studied

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

Refractory Multiple Myeloma
MedDRA version: 14.1 Level: PT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: PD 0332991
Product Code: na
Pharmaceutical Form: Capsule
INN or Proposed INN: na
Current Sponsor code: PD 0332991
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: PD 0332991
Product Code: na
Pharmaceutical Form: Capsule
INN or Proposed INN: na
Current Sponsor code: PD 0332991
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: na
Product Name: Bortezomib
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: Bortezomib
Other descriptive name: Bortezomib
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1-

Trade Name: na
Product Name: Dexamethasone
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Other descriptive name: DEXAMETHASONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: Phase I
? To determine the pharmacodynamic effects of PD 0332991 in combination with
bortezomib and dexamethasone in pre- and post-treatment serum and myeloma
specimens
? To evaluate the plasma pharmacokinetics of PD 0332991 when administered in
combination with bortezomib and dexamethasone to patients with refractory multiple
myeloma
? To document any clinical evidence of anti-tumor activity
Phase II
? To assess the safety of PD 0332991 in combination with bortezomib and dexamethasone
? To assess additional evidence of anti-tumor activity as measured by DR, PFS, TTP and OS
? To explore correlation of potential biomarkers with treatment-related outcomes
? To explore PRO

Main Objective: Phase I
? To determine the maximum tolerated dose (MTD) and RP2D of PD 0332991 in
combination with bortezomib and dexamethasone
Phase II
? To evaluate the anti-tumor activity of PD 0332991 in combination with bortezomib and dexamethasone based on ORR as defined by IMWGURC 9

Primary end point(s): ? Phase 1: First cycle DLTs to determine the MTD and RP2D of PD 0332991 in combination with
bortezomib and dexamethasone
? Phase 2: overall response rate of PD 0332991 in combination with bortezomib and dexamethasone as defined
by IMWGURC

Timepoint(s) of evaluation of this end point: na

Secondary Outcome(s)

Secondary end point(s): Phase 1:
? Changes in the phosphorylation status of the Rb protein in the myeloma cells, and changes in the tumor and soluble biomarkers (markers predictive of inhibition of tumor proliferation and/or induction of apoptosis) from samples collected pre andpost-treatment.
? Tumor response.
Phase 2:
? TTP, PFS and DR as defined by the IMWGURC.9
? OS.
? Overall safety profile characterized by type, incidence, severity, timing, seriousness and relationship to study medications of adverse events and any laboratory abnormalities.
? PRO as measured by the EORTC QLQ-C30, the QLQ-MY20, and the m-BPI-sf.

Timepoint(s) of evaluation of this end point: na

Secondary ID(s)

2010-022515-20-CZ

A5481004

Source(s) of Monetary Support

Pfizer Inc.