Plerixafor (AMD3100) and Bevacizumab for Recurrent High-Grade Glioma

NCT01339039 | Terminated Phase 1 DMC

• 2 other identifiers: 10-329MAMO0909-6
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

Plerixafor in combination with bevacizumab is a drug combination that may stop cancer cells from growing abnormally. Bevacizumab, also known as Avastin, is FDA approved for use in patients with recurrent glioblastoma and has been studied extensively in other types of solid tumors. Plerixafor, also known as Mozobil, is FDA approved for use in patients with non-Hodgkin's lymphoma and multiple myeloma and has been used in treatment for other cancers. Information from experiments in laboratories suggests that the combination of plerixafor and bevacizumab may help prevent the growth of gliomas. Part 1: The investigators are looking for the highest dose of plerixafor that can be given safely with bevacizumab (with a 21 days on/7 days off regimen of plerixafor). The investigators will also do blood tests to find out how the body uses and breaks down the drug combination. Part 2: The investigators are looking to see if plerixafor can get past the blood-brain barrier and into brain tumors. The investigators will also do blood tests to find out how the body uses and breaks down the drug combination. Part 3: The investigators are looking for for more information re: safety and tolerability of plerixafor in combination with bevacizumab (with a 28 days on/0 days off regimen of plerixafor). The investigators will also do blood tests to find out how the body uses and breaks down the drug combination.

Conditions

High Grade Glioma: Glioblastoma (GBM); High Grade Glioma: Gliosarcoma; Anaplastic Astrocytoma (AA); Anaplastic Oligodendroglioma (AO); Mixed Anaplastic Oligoastrocytoma (AOA)

Keywords

AMD3100; plerixafor; Mozobil; bevacizumab

Outcome Measures

Primary Outcomes (1)

• Determination of Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose (the highest dose combination that causes DLT in no more than 1 of 6 patients) of plerixafor 3 weeks on, 1 week off in combination with bevacizumab (every two weeks) in this patient population.

  9 months

Secondary Outcomes (7)

• Safety Evaluation (3 weeks on / 1 week off) - Assessment of the proportion of subjects with different grades of toxicities

  2 years

• Safety and Tolerability (daily plerixafor) - Assessment of the proportion of subjects with different grades of toxicities

  3 years

• Determination of Plasma PK Parameters

  2 years

• Exploratory Objective #1 - Preliminary data assessment on anti-tumor efficacy

  3 years

• Exploratory Objective #2 - Investigation of cerebrospinal fluid (CSF) penetration of plerixafor

  3 years

Study Arms (3)

Part 1

EXPERIMENTAL

Maximum Tolerated Dose Determination of Plerixafor (3 weeks on, 1 week off) and Bevacizumab (every 2 weeks)

Drug: Plerixafor; Drug: Bevacizumab

Part 2

EXPERIMENTAL

Surgical Arm: Safety evaluation of Plerixafor (3 weeks on, 1 week off) and Bevacizumab (every 2 weeks)

Drug: Plerixafor; Drug: Bevacizumab; Procedure: Surgery

Part 3

EXPERIMENTAL

Safety and tolerability of Plerixafor (daily) at MTD dose from Part 1 and Bevacizumab (every 2 weeks)

Drug: Plerixafor; Drug: Bevacizumab

Interventions

Plerixafor DRUG

Given subcutaneously once a day for 3 weeks followed by 1 week off (standard 3x3 design); MTD determined in Part 1 will be used as dose in Part 2.

Also known as: AMD3100, Mozobil

Part 1; Part 2

Bevacizumab DRUG

Given intravenously on days 1 and 15 (10 mg/kg) of each 28-day cycle

Also known as: Avastin

Part 1; Part 2; Part 3

Surgery PROCEDURE

After receiving 5-9 days of Plerixafor (AMD3100) monotherapy, patients proceed to surgery. After recovering from surgery, patients will proceed to 28-day post-surgical cycles of therapy (Plerixafor at the MTD established in Part 1, 21 days on / 7 days off; bevacizumab 10 mg/kg on days 1 \& 15).

Part 2

Eligibility Criteria

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

You may qualify if:

• Histologic diagnosis of glioblastoma (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), or anaplastic mixed oligoastrocytoma (AOA). Patients are eligible if the original histology was lower-grade glioma.
• Unequivocal progression by MRI or CT
• Patients with recurrence who undergo resection and are left without measurable or evaluable disease are eligible.
• Patients must have recurrent disease and may have had any number of prior relapses (including no prior relapses) on NON-anti-VEGF(R) containing regimens. Relapse is defined as progression following initial therapy. For patients who progressed on a prior anti-VEGF(R) containing regimen including bevacizumab, only one prior relapse on an anti-VEGF(R) containing regimen is allowed.
• years of age or older
• Karnofsky performance status of 60 or greater
• Normal organ and marrow function as outlined in the protocol
• Ability to understand and willingness to sign a written informed consent document.
• Protocol treatment must begin within 5 consecutive days after registration
• Patients enrolled in Part 2 must be willing to undergo surgical resection and have sufficient pre-treatment archival tumor tissue available for molecular analysis
• Women of child-bearing potential must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product. In addition, female subjects of child-bearing potential and male subjects with partners of child-bearing potential must agree to use an effective means of birth control while on study therapy and for a minimum of 4 months following last plerixafor dose and 6 months following last bevacizumab dose.
• Effective birth control includes:
• birth control pills, depot progesterone, or an intrauterine device plus one barrier method;
• or 2 barrier methods. Effective barrier methods are male and female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). Hormonal contraceptive methods are not sufficient, as information about any interaction of plerixafor with hormonal contraceptives is not known.

You may not qualify if:

• Patients who have had prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C). Patients must be off treatment with Temozolomide for at least 23 days. Patients who received non-cytotoxic drug therapy must be off treatment for at least 2 weeks. For patients enrolling in Part 1 or Part 3 AND who have progressed on a prior bevacizumab-containing regimen, patients may continue treatment with bevacizumab 10 mg/kg monotherapy, with last dose of bevacizumab administered no fewer than 14 days from start of Plerixafor and bevacizumab. For participants enrolling in Part 1 or Part 3 AND who have progressed on a prior anti-VEGF(R) (other than bevacizumab) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days before receiving Plerixafor and bevacizumab. For patients enrolled in Part 2 (surgical substudy) AND who have progressed on a prior bevacizumab or other anti-VEGF(R) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days prior to surgery.
• NOTE: Participants must have recovered to a grade 0 or 1 from any clinically significant toxicity related to prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide). For any patient who received prior bevacizumab or an anti-VEGF(R) therapy, patient must NOT have discontinued that treatment regimen due to a treatment-related toxicity.
• In order to prevent registering patients with pseudoprogression rather than true disease progression, patients must not have received any form of cranial radiation within 12 weeks of study entry.
• NOTE: Patients who have received cranial radiation within 12 weeks of study entry will be allowed to register to trial only if progressive disease is confirmed via biopsy.
• Major surgical procedure (including craniotomy) or significant traumatic injury less than 28 days or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 7 days.
• Patients may not be receiving any other investigational agents within the past 28 days.
• NOTE: If agent's half-life x 5 is \< 28 days, patient may have taken it within the last 28 days, provided at least 5 half-lives have passed since having last taken it.
• Patients who have had prior therapy with CXCR4 inhibitors.
• Patients with one prior relapse on a bevacizumab or an anti-VEGF(R) (i.e. VEGF-trap, vandetanib, cediranib, sunitinib, sorafenib, XL184, etc.) containing regimen are allowed to participate.
• Prior therapy with thalidomide and lenalidomide is allowed.
• Patients who have received prior treatment with implanted radiotherapy or chemotherapy sources such as wafers of polifeprosan 20 with carmustine (e.g. Gliadel wafers).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to plerixafor or bevacizumab.
• For the first 20 patients to register, no anti-coagulation is allowed; for all subsequent patients screened, patients requiring therapeutic anticoagulation with warfarin at baseline are excluded (however, therapeutic or prophylactic therapy with a low-molecular weight heparin is acceptable).
• Patients must not have a known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhages in the past.
• Patients whose MRI scan demonstrates intratumoral hemorrhage or peritumoral hemorrhage are not eligible for treatment if deemed significant by the treating physician.

Sponsors & Collaborators

• Patrick Y. Wen, MD: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Massachusetts General Hospital: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma

Interventions

plerixafor; Bevacizumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Patrick Y. Wen, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Disease Center Leader, Center For Neuro-Oncology

Study Record Dates

• First Submitted: April 6, 2011
• First Posted: April 20, 2011
• Study Start: December 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 8, 2017
• Last Updated: November 17, 2017

Record last verified: 2017-11

Locations

US (2)