Poly-ICLC: Biological Therapy and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00052715
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 31
• Location: 1
• Arm: 1
• Actual Duration (Months): 74.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies such as poly-ICLC use different ways to stimulate the immune system and stop tumor cells from growing. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining biological therapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining poly-ICLC with radiation therapy in treating patients who have newly diagnosed glioblastoma multiforme.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors	Drug: poly ICLC	Phase 2

Detailed Description

OBJECTIVES:

• Determine the efficacy of poly ICLC and radiotherapy, in terms of total survival from date of diagnosis, in patients with newly diagnosed glioblastoma multiforme.

• Determine the safety and toxicity profile of this regimen in these patients.

• Determine the 12-month survival rate in patients treated with this regimen.

• Assess progression-free survival at 6 months and median progression-free survival from date of diagnosis of patients treated with this regimen.

• Assess response in patients treated with this regimen.

• Assess changes in neurological status in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Within 1-4 weeks after surgery, patients receive poly ICLC intramuscularly 3 times weekly (on days 1, 3, and 5). Treatment continues in the absence of disease progression or unacceptable toxicity.

One week after the initiation of poly ICLC, patients undergo external beam radiotherapy once daily 5 days a week for 6 weeks.

Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial Of Poly-ICLC For Glioblastoma
• Actual Study Start Date: Oct 23, 2002
• Actual Primary Completion Date: Feb 25, 2006
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: poly-ICLC Newly diagnosed GBM Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC	Drug: poly ICLC

Outcome Measures

Primary Outcome Measures

1. Overall Survival in Pts With Newly Diagnosed GBM [2 years]

   Overall survival from surgical diagnosis in patients with Newly Diagnosed GBM

Secondary Outcome Measures

1. To Determine 6 Months Progression Free Survival [6 months]

   Patients evaluated from date of diagnosis to the 6 month scan

2. Determine the 12-month Survival Rate [1 year]

   12-month survival rate calculated from date of diagnosis

3. to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients [2 years]

   CTCAE 4

4. To Determine the Change in Neurological Status in Patients With Glioblastoma Treated With External Beam Radiotherapy and Poly-ICLC [1 year]

   Descriptive measure per investigator to describe change in neurological status post-intervention.

5. To Determine Tumor Response [2 years]

   Tumor response to treatment with Poly-ICLC

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma by biopsy or resection within the past 28 days

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• More than 8 weeks

Hematopoietic

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic

• Bilirubin less than 2 times upper limit of normal (ULN)

• SGOT less than 2 times ULN

Renal

• Creatinine less than 1.5 mg/dL

Other

• No significant medical illness that cannot be controlled adequately with appropriate therapy or that would compromise tolerability of study therapy

• No other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission and off all therapy for that disease for at least 3 years

• No active infection

• No disease that would obscure toxicity or dangerously alter drug metabolism

• No other serious concurrent medical illness

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior polifeprosan 20 with carmustine implant (Gliadel wafer)

• No concurrent chemotherapy

Endocrine therapy

• Concurrent corticosteroids to treat symptoms or prevent complications are allowed

Radiotherapy

• No prior radiotherapy to the brain

• No concurrent stereotactic radiosurgery

• No concurrent brachytherapy

Surgery

• See Disease Characteristics

Other

• No prior cytotoxic or noncytotoxic drug therapy for GBM

• No prior experimental drug therapy for GBM

• No other concurrent cytotoxic or noncytotoxic drug therapy for GBM

• Concurrent analgesics, antiepileptics, or other drugs to treat symptoms or prevent complications are allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Prados, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00052715
• Other Study ID Numbers: NABTC-0105; CDR0000258685; NCI-2012-02506
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 18, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma
• Additional relevant MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms; Poly ICLC

Study Results

Participant Flow

Recruitment Details	Patients enrolled from 7/14/2003 through 12/19/2005. Patients recruited from outpatient clinic centers.

Arm/Group Title	Poly-ICLC
Arm/Group Description	poly-ICLC given at dose of 20mcg/kg 3 times weeekly by intramusclular injection. days of administration were at least 2 days apart. Mon-Wed-fri Poly-ICLC drug poly ICLC
Period Title: Overall Study
STARTED	31
COMPLETED	30
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Poly-ICLC
Arm/Group Description	poly-ICLC given at dose of 20mcg/kg 3 times weeekly by intramusclular injection. days of administration were at least 2 days apart. Mon-Wed-fri Poly-ICLC drug poly ICLC
Overall Participants	30
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	16 53.3%
Male	14 46.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.3%
White	27 90%
More than one race	0 0%
Unknown or Not Reported	1 3.3%
Karnofsky Performance Status Scale (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	90
Histology Glioblastoma (participants) [Number]
Number [participants]	30 100%
Extent of Resection (Count of Participants)
Biopsy	2 6.7%
Subtotal resection	17 56.7%
Gross Total resection	11 36.7%

Outcome Measures

1. Primary Outcome

Title	Overall Survival in Pts With Newly Diagnosed GBM
Description	Overall survival from surgical diagnosis in patients with Newly Diagnosed GBM
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Four patents were censored for survival at 35, 114, 126, and 166 weeks

Arm/Group Title	Poly-ICLC Newly Diagnosed GBM
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	30
Median (95% Confidence Interval) [weeks]	65

2. Secondary Outcome

Title	To Determine 6 Months Progression Free Survival
Description	Patients evaluated from date of diagnosis to the 6 month scan
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Poly-ICLC Newly Diagnosed GBM
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	30
Number [percentage of participants]	30 100%

3. Secondary Outcome

Title	Determine the 12-month Survival Rate
Description	12-month survival rate calculated from date of diagnosis
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Poly-ICLC Newly Diagnosed GBM
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	30
Number [percent of participants]	69 230%

4. Secondary Outcome

Title	to Determine Grade 3 and 4 Toxicities Associated With Poly-ICLC in Newly Diagnosed Patients
Description	CTCAE 4
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Poly-ICLC Newly Diagnosed GBM
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	30
Fatigue	4 13.3%
Leukopenia	4 13.3%
Lymphocytopenia	2 6.7%
Myalgia	1 3.3%
Fever without infection	1 3.3%
Thrombosis	2 6.7%
Pain	1 3.3%
Rigor/Chills	1 3.3%

5. Secondary Outcome

Title	To Determine the Change in Neurological Status in Patients With Glioblastoma Treated With External Beam Radiotherapy and Poly-ICLC
Description	Descriptive measure per investigator to describe change in neurological status post-intervention.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure due to premature discontinuation of study agent in response to what turned out to be pseudo-progression.

Arm/Group Title	Poly-ICLC Newly Diagnosed GBM
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	0

6. Secondary Outcome

Title	To Determine Tumor Response
Description	Tumor response to treatment with Poly-ICLC
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure due to reports of transient enlargement of contrast enhancing disease with subsequent shrinkage during Poly-ICLC treatment and the lack of central radiological review, the protocol defined criteria for radiological response could not be employed because of the risk of inconsistent results

Arm/Group Title	Poly-ICLC Newly Diagnosed GBM
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week (Monday-Wednesday-Friday) starting one week before Radiation Therapy Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	0

Adverse Events

Time Frame	2 years
Arm/Group Title	Poly-ICLC
Arm/Group Description	poly-ICLC given at dose of 20mcg/kg 3 times weeekly by intramusclular injection. days of administration were at least 2 days apart. Mon-Wed-fri Poly-ICLC drug poly ICLC
All Cause Mortality
	Poly-ICLC
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Serious Adverse Events
	Poly-ICLC
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	Poly-ICLC
	Affected / at Risk (%)	# Events
Total	30/30 (100%)
Blood and lymphatic system disorders
Lymphocytopenia	9/30 (30%)	9
Granulocytopenia	7/30 (23.3%)	7
Leukopenia	4/30 (13.3%)	4
Gastrointestinal disorders
nausea	5/30 (16.7%)	5
Anorexia	4/30 (13.3%)	4
Diarrhea	4/30 (13.3%)	4
Weight Loss	3/30 (10%)	3
Gastrointestinal Other	2/30 (6.7%)	2
General disorders
Fatigue	24/30 (80%)	24
Rigors/chills	9/30 (30%)	9
Fever	4/30 (13.3%)	4
Infections and infestations
Infection Other	2/30 (6.7%)	2
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)	2/30 (6.7%)	2
Investigations
Alanine Aminotransferase Increased	7/30 (23.3%)	7
Alkaline Phosphatase Increased	6/30 (20%)	6
Aspartate Aminotransferase Increased	6/30 (20%)	6
Blood Bilirubin Increase	2/30 (6.7%)	2
Musculoskeletal and connective tissue disorders
Pain (Other)	11/30 (36.7%)	11
Myalgia	10/30 (33.3%)	10
Arthralgia	2/30 (6.7%)	2
Nervous system disorders
Headache	6/30 (20%)	6
Seizure	2/30 (6.7%)	2
Neuropathy Sensory	2/30 (6.7%)	2
Speech Impairment	2/30 (6.7%)	2
Skin and subcutaneous tissue disorders
alopecia	4/30 (13.3%)	4
Hyperidrosis	2/30 (6.7%)	2
Rash	2/30 (6.7%)	2

Limitations/Caveats

Enrollment was prematurely discontinued after the results of the EORTC phase-3 study defined the standard of care for newly diagnosed glioblastoma patients as radiotherapy plus concomitant and adjuvant temozolomide (2005)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.