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Trial record 52 of 108 for:    hedgehog

A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT02038777
Recruitment Status : Recruiting
First Posted : January 17, 2014
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is an open-label, multi-center, Phase 1 study of PF-04449913 in Japanese patients. PF-04449913 will be administered orally as a single agent in patients with select advanced hematologic malignancies, or in combination with LDAC [Low-Dose Ara-C] or cytarabine and daunorubicin in previously untreated patients with AML [Acute Myeloid Leukemia] or high-risk MDS [Myelodysplastic Syndrome], or in combination with azacitidine in previously untreated patients with AML.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: PF-04449913 Drug: Low dose ARA-C (LDAC) Drug: Daunorubicin Drug: Cytarabine Drug: Azacitidine Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model Description: MTD was determined in monotherapy cohort. Then two combination cohorts (Combination Cohorts 1 and 2) were added to evaluate the safety of glasdegib administered with chemotherapies. Another combination cohort (Combination Cohort 3) was added to evaluate the safety of glasdegib administered with Azacitidine. Then, Continuation Cohort which allows one Japanese patient enrolled from another trial in the same project was added.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Pf-04449913 (Glasdegib), An Oral Hedgehog Inhibitor, Administered As A Single Agent In Japanese Patients With Select Hematologic Malignancies And In Combination With Intensive Chemotherapy, Low-dose Ara-c, Or Azacitidine In Patients With Acute Myeloid Leukemia Or High-risk Myelodysplastic Syndrome
Actual Study Start Date : March 25, 2014
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019


Arm Intervention/treatment
Experimental: Monotherapy Cohort
PF-04449913 Monotherapy
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Experimental: Combination Cohort 1
PF-04449913 in combination with low dose ARA-C (LDAC)
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: Low dose ARA-C (LDAC)
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.

Experimental: Combination Cohort 2
PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: Daunorubicin
Daunorubicin given using 60 mg/m2 for 3-days.

Drug: Cytarabine
Cytarabine 100 mg/m2 on days 1 through 7.

Experimental: Azacitidine Combination Cohort
PF-04449913 in combination with azacitidine
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: Azacitidine
Azacitidine Combination Cohort; Azacitidine 75 mg/m2 for 7 days.

Experimental: Continuation Cohort
PF-04449913 Monotherapy for one patient rolled-over from another trial in the same project.
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.




Primary Outcome Measures :
  1. First cycle Dose Limiting Toxicities [ Time Frame: 28 days after first dose ]

Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ Time Frame: 12 months ]
  2. Time to reach maximum observed plasma concentration (Tmax) [ Time Frame: 12 months ]
  3. Area under the plasma concentration curve (AUC) [ Time Frame: 12 months ]
  4. Objective disease response [ Time Frame: 12 months ]
  5. Disease-related gene mutation (PD biomarkers) [ Time Frame: 12 months ]
  6. Detectable tumor Gli1 expression (PD Biomarkers) [ Time Frame: 12 months ]
  7. Overall Survival (OS) [ Time Frame: 3 years ]
    For Azacitidine Combination Cohort only

  8. Probability of Participant Survival [ Time Frame: 1 years ]
    For Combination Cohort 1 only



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with select advanced hematologic malignancies who are refractory, resistant or intolerant to prior therapies for monotherapy cohort.
  • Patients with AML or High-Risk MDS who are newly diagnosed and previously untreated for combination cohort.
  • Patients with AML who are newly diagnosed and previously untreated for azacitidine combination cohort.
  • ECOG [Eastern Cooperative Oncology Group] performance status 0 to 2
  • Adequate organ function

Exclusion Criteria:

  • Patients with active CNS disease
  • Patient with active malignancy with the exception of basal cell carcinoma, non melanoma skin cancer, carcinoma in situ cervical
  • Patient has an active, life threatening or clinically significant uncontrolled systemic infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02038777


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
Japan
Japanese Red Cross Nagoya First Hospital Recruiting
Nagoya, Aichi, Japan, 453-8511
Kobe University Hospital Recruiting
Kobe-shi, Hyogo, Japan, 650-0017
Tohoku University Hospital Recruiting
Sendai, Miyagi, Japan, 980-8574
National Cancer Center Hospital Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Akita University Hospital Recruiting
Akita, Japan, 010-8543
Kyushu University Hospital Recruiting
Fukuoka, Japan, 812-8582
Tokyo Medical University Hospital Recruiting
Tokyo, Japan, 160-0023
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02038777     History of Changes
Other Study ID Numbers: B1371005
First Posted: January 17, 2014    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:
Hematologic Malignancies

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Azacitidine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors