A Study of PD 0332991 in Patients With Recurrent Rb Positive Glioblastoma

NCT01227434 | Terminated Phase 2 Results DMC

• 1 other identifier: 10105
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the efficacy of the small molecule CDK4/6 inhibitor PD 0332991 (as measured by progression free survival at 6 months) in patients with recurrent glioblastoma multiforme or gliosarcoma who are Rb positive. A total of 30 patients will be treated; 15 will undergo a planned surgical resection and receive drug for 7 days prior to surgery, followed by drug after recovery from surgery, and the other 15 patients will receive drug without a planned surgical procedure.

Conditions

Glioblastoma; Gliosarcoma; Anaplastic Astrocytoma

Keywords

Glioblastoma; Gliosarcoma; Anaplastic astrocytoma; Malignant astrocytoma NOS; Malignant glioma; GBM

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Efficacy of the small molecule CDK4/6 inhibitor PD 0332991 in patients with recurrent glioblastoma multiforme or gliosarcoma who are Rb positive was measured by progression free survival. A total of 30 patients was intended to be treated; up to 15 patients were to undergo a planned, intended surgical resection and receive drug for 7 days prior to surgery, followed by drug after recovery from surgery; and up to 15 patients were to receive drug without a planned surgical procedure.

  up to 142 weeks

Secondary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  1-2 years

Study Arms (2)

Surgical Group

EXPERIMENTAL

PD 0332991 125 mg daily for 7 days prior to an indicated, intended surgical resection as clinical care for progression, and then resume drug at the same dose after recovery from surgery on a repeating schedule of 21 consecutive days of drug followed by a 7 day break off therapy (cycle length is 28 days). Treatment will be repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients will be given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.

Drug: PD 0332991 (pre-surgery); Drug: PD 0332991; Procedure: Resection as clinical care

Non-surgical group

EXPERIMENTAL

Patients not in need of surgery treated with PD 0332991 125 mg daily for 21 consecutive days followed by a 7 day break off therapy (cycle length is 28 days). Treatment will be repeated every 28 days, and in the absence of disease progression patients may receive treatment for 12 cycles. At that time patients will be given the option to continue on study past 12 cycles, up to a maximum of 24 cycles.

Drug: PD 0332991

Interventions

PD 0332991 (pre-surgery) DRUG

PD 0332991 for 7 days prior to an indicated, intended surgical resection for progression

Also known as: Pfizer PD 0332991, palbociclib, IBRANCE, Pfizer, Inc.

Surgical Group

PD 0332991 DRUG

PD 0332991 daily for 21 consecutive days followed by a 7 day break off therapy, repeating cycles

Also known as: Pfizer PD 0332991, palbociclib, IBRANCE, Pfizer, Inc.

Non-surgical group; Surgical Group

Resection as clinical care PROCEDURE

Indicated, intended, surgical resection as clinical care

Surgical Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years or older with KPS \> 60, with life expectancy of \> 8 weeks with radiographically proven recurrent, intracranial Glioblastoma multiforme or Gliosarcoma; patients must have documentation of Rb positive disease.
• All patients must sign an informed consent and must have signed an authorization for the release of their protected health information.
• Patients must have had prior external beam radiation and temozolomide chemotherapy; there is no limit to the number of prior chemotherapies used; patients may be treated in their first, second or third relapse
• Patients must have recovered from the toxic effects of prior therapy
• Patients must have adequate bone marrow function and renal function before starting therapy. A pre-study EKG with a normal QT interval is required for all patients
• Patients must have shown unequivocal evidence for tumor progression by MRI scan and on a steroid dose that has been stable for at least 7 days.
• Patients must have an interval of greater than or equal to 42 days from the completion of radiation therapy to study entry.
• A subset of 15 patients will be enrolled prior to a planned, indicated surgical resection. Patients can be enrolled pre-operatively only if they are surgical candidates, do not have evidence of an acute intracranial hemorrhage and are able to start protocol treatment in a window of 7 days before surgery.
• Male and female patients with reproductive potential must use an approved contraceptive method. Women of childbearing potential must have a negative beta-HCG pregnancy test
• Blocks or slides of tumor tissue from a previous surgery must be available to do IHC Rb staining. Patients with negative tumors (Rb negative) will be excluded from the study.

You may not qualify if:

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• Patients on enzyme-inducing anti-epileptic drugs or other drugs that cause CYP3A enzyme induction or inhibition will not be eligible

Sponsors & Collaborators

• University of California, San Francisco: lead
• Pfizer: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• Taylor JW, Parikh M, Phillips JJ, James CD, Molinaro AM, Butowski NA, Clarke JL, Oberheim-Bush NA, Chang SM, Berger MS, Prados M. Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma. J Neurooncol. 2018 Nov;140(2):477-483. doi: 10.1007/s11060-018-2977-3. Epub 2018 Aug 27.

  PMID: 30151703 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Astrocytoma; Glioma

Interventions

palbociclib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Michael Prados, MD
• Organization: University of California San Francisco

pradosm@neurosurg.ucsf.edu

4154767217

Study Officials

• Michael D Prados, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 25, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: July 17, 2015
• Results First Posted: June 12, 2015

Record last verified: 2015-06

Locations

US (1)