Trial Outcomes & Findings for Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma (NCT NCT00589875)

NCT ID: NCT00589875

Last Updated: 2024-04-03

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 52 participants
• Primary outcome timeframe: 2 months
• Results posted on: 2024-04-03

Participant Flow

Participant milestones

Measure	Single Arm This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.
Enrollment to Treatment Initiation STARTED	52
Enrollment to Treatment Initiation COMPLETED	43
Enrollment to Treatment Initiation NOT COMPLETED	9
Treatment Initiation to Completion STARTED	43
Treatment Initiation to Completion COMPLETED	36
Treatment Initiation to Completion NOT COMPLETED	7

Reasons for withdrawal

Measure	Single Arm This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.
Enrollment to Treatment Initiation Patients ineligable for study.	9
Treatment Initiation to Completion Treatment discontinuation	7

Baseline Characteristics

9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.

Baseline characteristics by cohort

Measure	Single Arm n=43 Participants This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.
Age, Categorical <=18 years	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Age, Categorical >=65 years	10 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Sex: Female, Male Female	13 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Sex: Female, Male Male	30 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) Asian	2 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) White	41 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) More than one race	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants • 9 patients were withdrawn from the study prior to receiving treatment due to pathology inconsistent with malignant glioma.

PRIMARY outcome

Timeframe: 2 months

Outcome measures

Measure

Single Arm n=43 Participants This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.

Number of Participants With Treatment Related Adverse Events

21 Participants

SECONDARY outcome

Timeframe: 5 years

Outcome measures

Measure

Single Arm n=36 Participants This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.

Overall Survival

18.15 Months Interval 13.6 to 25.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Outcome measures

Outcome data not reported

Adverse Events

Single Arm

Serious events: 20 serious events

Other events: 40 other events

Deaths: 41 deaths

Serious adverse events

Measure	Single Arm n=43 participants at risk This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.
Cardiac disorders Arrhythmia	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
General disorders Fever	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Gastrointestinal disorders Dehydration	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Hepatobiliary disorders Pancreatitis	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Infections and infestations Wound Infection	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Cerebral Edema	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Cognitive Disturbance	4.7% 2/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Generalized Weakness	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Mood Alteration - Agitation	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Mood Alteration - Depression	4.7% 2/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Seizure	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Fall	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Headache	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Surgical and medical procedures Cystic Fluid Collection	2.3% 1/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Vascular disorders Thrombosis Embolism	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years

Other adverse events

Measure	Single Arm n=43 participants at risk This study is an extension of evaluation of the surgical resection arm, Arm B, from a phase Ib study in which dose escalation on arm B was completed. CAN-2409: Single dose of 3x10e11 vector particles of CAN-2409 delivered to the tumor bed after resection on day 0. Valacyclovir: Single course of valacyclovir at dose of 2 grams orally three times per day for 14 days starting on day 1-3 Temozolomide: Concomitant TMZ will be administered orally once a day at a dose of 75 mg/m2 starting the next day after completing prodrug and continued for 6 weeks. Adjuvant TMZ will be administered days 1 to 5 of a 28-day cycle for 6 cycles with 150 mg/m2 administered for cycle 1, and 150 to 200 mg/m2 administered for cycles 2 to 6. Adjuvant treatment will start 1 month following completing RT. Radiation therapy: Radiation will be administered to up-front patients as per standard of care for the patient. It will start 3-7 days after CAN-2409 injection, preferably closer to 3 days. It will consist of standard external field radiation, limited to the area of tumor and brain adjacent to tumor, fractionated at doses of 200cGy per day for approximately 6 weeks to a total of 5500-6000 cGy.
Skin and subcutaneous tissue disorders Rash	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Gastrointestinal disorders Anorexia	16.3% 7/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Gastrointestinal disorders Constipation	20.9% 9/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Gastrointestinal disorders Nausea	14.0% 6/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Gastrointestinal disorders Taste Alteration	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Renal and urinary disorders Urinary Tract Infection	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Blood and lymphatic system disorders Edema	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Musculoskeletal and connective tissue disorders Muscle Weakness	11.6% 5/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Ataxia	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Cerebral Edema	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Cognitive Disturbance	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Memory Impairment	16.3% 7/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Mood Alteration - Agitation	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Mood Alteration - Anxiety	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Mood Alteration - Depression	20.9% 9/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Neuropathy - Motor	11.6% 5/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Seizure	25.6% 11/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Speech Impairment	20.9% 9/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Nervous system disorders Headache	48.8% 21/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Surgical and medical procedures Incision Site Pain	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Vascular disorders Thrombosis Embolism	11.6% 5/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
General disorders Insomnia	20.9% 9/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Ear and labyrinth disorders Tinnitus	7.0% 3/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
General disorders Fatigue	51.2% 22/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
General disorders Fever	16.3% 7/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years
Skin and subcutaneous tissue disorders Alopecia	9.3% 4/43 • Adverse events were assessed up to 2 months. All-Cause Mortality was assessed up to 5 years

Additional Information

Garrett Nichols (CMO)

Candel Therapeutics

Phone: 617-916-5445

Email: Gnichols@candeltx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place