Poly-ICLC in Treating Patients With Recurrent or Progressive Anaplastic Glioma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00058123
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 55
• Locations: 8
• Arm: 1
• Actual Duration (Months): 69.9
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.1

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.

PURPOSE: This phase II trial is studying how poly-ICLC works in treating patients with recurrent, progressive, or relapsed anaplastic glioma.

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

Detailed Description

OBJECTIVES:

• Determine the objective response rate in patients with recurrent or progressive anaplastic glioma treated with poly ICLC.

• Determine the efficacy of this drug, in terms of 6-month progression-free survival, in these patients.

• Determine the safety profile of this drug in these patients.

• Determine the survival of patients treated with this drug.

• Determine the tumor response rate in patients treated with this drug.

• Determine the biological effects of this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive poly ICLC intramuscularly 3 times a week for 4 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 22-46 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 55 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Poly ICLC in Patients With Recurrent Anaplastic Glioma
• Actual Study Start Date: Mar 7, 2003
• Actual Primary Completion Date: Oct 6, 2007
• Actual Study Completion Date: Jan 2, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Poly-ICLC Recurrent gliomas Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection Drug Poly-ICLC	Drug: poly ICLC

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Objective Response Rate (ORR) [2 years]

   Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). ORR = CR + PR

2. Percentage of Participants With Progression Free Survival [6 months]

   Participants evaluated from date of study entry to the 6 month scan for progression

Secondary Outcome Measures

1. Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas [2 years]

   Toxicities defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0

2. Overall Survival [2 years]

   based on date of study entry

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 anaplastic glioma, including any of the following subtypes:

• Anaplastic astrocytoma

• Anaplastic oligodendroglioma

• Anaplastic mixed oligoastrocytoma

• Other anaplastic gliomas NOTE: Patients with an original histology of low-grade glioma are allowed provided a subsequent histological diagnosis of an anaplastic glioma is made

• Must have evidence of tumor recurrence or progression by MRI or CT scan* NOTE: *Steroid dose must be stable for at least 5 days before scan

• Prior radiotherapy required

• Patients who have had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis by positron-emission tomography, thallium scanning, magnetic resonance spectroscopy, or surgical documentation of disease

• Relapsed disease

• Progression after initial therapy (e.g., radiotherapy with or without chemotherapy)

• No more than 3 prior therapies (initial therapy and treatment for no more than 2 prior relapses)

• Surgical resection for relapsed disease with no anticancer therapy for up to 12 weeks followed by another surgical resection is considered 1 relapse

• For patients who have had prior therapy for a low-grade glioma, the surgical diagnosis of high-grade glioma is considered the first relapse

• Must be registered in the North American Brain Tumor Consortium Data Management Center database

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

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other cancer within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

• No active infection

• No concurrent serious medical illness

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

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 1 week since prior interferon or thalidomide

• No prior poly ICLC

Chemotherapy

• See Disease Characteristics

• At least 2 weeks since prior vincristine

• At least 3 weeks since prior procarbazine

• At least 6 weeks since prior nitrosoureas

• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

• At least 1 week since prior tamoxifen

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• Recovered from all prior therapy

• At least 1 week since other prior noncytotoxic agents (e.g., isotretinoin), excluding radiosensitizers

• At least 4 weeks since prior cytotoxic therapy

• At least 4 weeks since prior investigational agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
2	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
3	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
5	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
6	M.D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
7	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-6220
8	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164

Sponsors and Collaborators

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

Investigators

• Study Chair: Susan M. Chang, 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: NCT00058123
• Other Study ID Numbers: NABTC-0106 CDR0000287012; U01CA062399; NABTC-0106
• First Posted: Apr 9, 2003
• Last Update Posted: Aug 21, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• 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 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: adult anaplastic astrocytoma; adult mixed glioma; adult anaplastic oligodendroglioma; recurrent adult brain tumor; adult anaplastic ependymoma
• Additional relevant MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms; Poly ICLC

Study Results

Participant Flow

Recruitment Details	55 patients enrolled between 7/14/2003 and 12/192005 at Outpatient Clinical Centers

Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection poly ICLC
Period Title: Overall Study
STARTED	55
COMPLETED	45
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection poly ICLC
Overall Participants	45
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	43
Sex: Female, Male (Count of Participants)
Female	23 51.1%
Male	22 48.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 4.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 4.4%
White	40 88.9%
More than one race	0 0%
Unknown or Not Reported	1 2.2%
Karnofsky Performance Status Scale (units on a scale) [Median (Full Range) ]
Median (Full Range) [units on a scale]	90
Histology (participants) [Number]
Anaplastic Astrocytoma	32 71.1%
Anaplastic Oligodendroglioma	10 22.2%
Anaplastic Mixed Oligoastrocytoma	3 6.7%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Objective Response Rate (ORR)
Description	Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). ORR = CR + PR
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection Drug Poly-ICLC poly ICLC
Measure Participants	45
Count of Participants [Participants]	5 11.1%

2. Primary Outcome

Title	Percentage of Participants With Progression Free Survival
Description	Participants evaluated from date of study entry to the 6 month scan for progression
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection poly ICLC
Measure Participants	45
Number [percentage of participants]	24 53.3%

3. Secondary Outcome

Title	Number if Participants With Grade 3 and 4 Toxicities Associated With Poly-ICLC in Recurrent Gliomas
Description	Toxicities defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection poly ICLC
Measure Participants	45
Dyspnea	1 2.2%
Elevated Alanin Aminotransferase	4 8.9%
Hypoxia	1 2.2%
Leukopenia	2 4.4%
Muscle Weakness	1 2.2%
Elevated Sodium	1 2.2%
Tremors	2 4.4%

4. Secondary Outcome

Title	Overall Survival
Description	based on date of study entry
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Survival time was known for all 45 patients and 13 patients were censored as they were alive at last contact

Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection poly ICLC
Measure Participants	45
Median (95% Confidence Interval) [weeks]	43

Adverse Events

Time Frame	2 years
Arm/Group Title	Poly-ICLC Recurrent Gliomas
Arm/Group Description	Poly-ICLC 20ug/kg 3 times a week 4 week cycles (Monday-Wednesday-Friday) Intramuscular injection poly ICLC
All Cause Mortality
	Poly-ICLC Recurrent Gliomas
	Affected / at Risk (%)	# Events
Total	0/45 (0%)
Serious Adverse Events
	Poly-ICLC Recurrent Gliomas
	Affected / at Risk (%)	# Events
Total	0/45 (0%)
Other (Not Including Serious) Adverse Events
	Poly-ICLC Recurrent Gliomas
	Affected / at Risk (%)	# Events
Total	45/45 (100%)
General disorders
fatigue	28/45 (62.2%)	28
Investigations
Elevated Alanine Transferase	13/45 (28.9%)	13
Granulocytopenia	7/45 (15.6%)	7
Leukopenia	13/45 (28.9%)	13
Lymphocytopenia	5/45 (11.1%)	5
Skin and subcutaneous tissue disorders
injection site reaction	3/45 (6.7%)	3

Limitations/Caveats

[Not Specified]

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.