Condition or disease | Intervention/treatment | Phase |
---|---|---|
Human Papillomavirus-16 Positive Human Papillomavirus-18 Positive Metastatic Malignant Neoplasm Recurrent Anal Canal Carcinoma Recurrent Cervical Carcinoma Recurrent Malignant Neoplasm Recurrent Penile Carcinoma Recurrent Vaginal Carcinoma Recurrent Vulvar Carcinoma Refractory Malignant Neoplasm Stage IV Anal Cancer AJCC v8 Stage IV Cervical Cancer AJCC v8 Stage IV Penile Cancer AJCC v8 Stage IV Vaginal Cancer AJCC v8 Stage IV Vulvar Cancer AJCC v8 Stage IVA Cervical Cancer AJCC v8 Stage IVA Vaginal Cancer AJCC v8 Stage IVA Vulvar Cancer AJCC v8 Stage IVB Cervical Cancer AJCC v8 Stage IVB Vaginal Cancer AJCC v8 Stage IVB Vulvar Cancer AJCC v8 | Biological: DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine MEDI0457 Biological: Durvalumab | Phase 2 |
PRIMARY OBJECTIVES:
I. To evaluate the anti-tumor activity of DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 (MEDI0457) in combination with durvalumab.
SECONDARY OBJECTIVES:
I. To determine the safety profile of MEDI0457 in combination with durvalumab in patients with recurrent/metastatic human papilloma virus (HPV) 16- or 18- associated cancer.
II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients with recurrent/metastatic incurable HPV-16/18 positive solid malignancies receiving the combination of MEDI0457and durvalumab.
III. To evaluate objective response rate (ORR) by immune-related criteria of the combination of MEDI0457 and durvalumab in patients with recurrent/metastatic incurable HPV-16/18 positive solid malignancies.
IV. To evaluate the disease control rate at 24 weeks.
EXPLORATORY OBJECTIVES:
I. To determine the cellular and humoral immune response to immunotherapy with MEDI0457 in combination with durvalumab,
II. To examine the correlation between anti tumor activity and biomarkers including:
IIa. HPV-specific cellular and humoral responses. IIb. Programmed death ligand 1 status. IIc. The number of tumor infiltrating lymphocytes, HPV 16/18 E6/E7 deoxyribonucleic acid (DNA) levels and HPV 16/18 E6/E7 DNA sequence in biopsy tissue and plasma.
III. To evaluate the pharmacokinetics and anti-drug antibodies (ADA) for durvalumab.
OUTLINE:
Patients receive DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 intramuscularly (IM) and via electroporation at 1, 3, 7, and 12 weeks and durvalumab intravenously (IV) at 4, 8, and 12 weeks. Starting week 12, cycles repeat every 8 weeks for DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and every 4 weeks for up to 13 doses of durvalumab in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 90 days, every 3 months for 12 months, and then every 6 months thereafter.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 77 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2, Open-Label Study to Evaluate Efficacy of Combination Treatment With MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients With Recurrent/Metastatic Human Papilloma Virus Associated Cancers |
Actual Study Start Date : | November 14, 2018 |
Estimated Primary Completion Date : | December 31, 2021 |
Estimated Study Completion Date : | December 31, 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: Treatment (INO-3112, durvalumab)
Patients receive DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 IM and via electroporation at 1, 3, 7, and 12 weeks and durvalumab IV at 4, 8, and 12 weeks. Starting week 12, cycles repeat every 8 weeks for DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and every 4 weeks for up to 13 doses of durvalumab in the absence of disease progression or unacceptable toxicity.
|
Biological: DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine MEDI0457
Given IM and via electroporation
Other Names:
Biological: Durvalumab Given IV
Other Names:
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Hemoglobin >= 9 g/dL (Note: Note: No Transfusion within 7 days of beginning study treatment. Ongoing growth factor support is acceptable if on a stable dose for the past 56 days), within 28 days of day 0.
Absolute neutrophil count >= 1,000/mm^3, within 28 days of day 0.
Platelet count >= 100,000/mm^3 and no transfusion in prior 4 weeks, within 28 days of day 0.
Exclusion Criteria:
Receipt of live, attenuated vaccine within 30 days prior to study entry or the first dose of MEDI0457.
Contact: Michael M. Frumovitz, MD, MPH | 713-792-9599 | mfrumovitz@mdanderson.org |
United States, Texas | |
M D Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Michael M. Frumovitz 713-792-9599 | |
Principal Investigator: Michael M. Frumovitz |
Principal Investigator: | Michael M Frumovitz | M.D. Anderson Cancer Center |
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date ICMJE | February 14, 2018 | ||||
First Posted Date ICMJE | February 20, 2018 | ||||
Last Update Posted Date | December 2, 2020 | ||||
Actual Study Start Date ICMJE | November 14, 2018 | ||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Objective response rate (ORR) [ Time Frame: Up to 2 years ] Will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Will be estimated with 95% confidence interval.
|
||||
Original Primary Outcome Measures ICMJE |
Overall Response Rate (ORR) of MEDI0457 in Combination with Durvalumab Measured by RECIST v1.1 [ Time Frame: Start of drug combination up to 30 days after drug combination stopped up to 5 years. ] | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
|
||||
Original Secondary Outcome Measures ICMJE |
|
||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine INO-3112 and Durvalumab in Treating Patients With Recurrent or Metastatic Human Papillomavirus Associated Cancers | ||||
Official Title ICMJE | A Phase 2, Open-Label Study to Evaluate Efficacy of Combination Treatment With MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients With Recurrent/Metastatic Human Papilloma Virus Associated Cancers | ||||
Brief Summary | This phase II trial studies how well deoxyribonucleic acid (DNA) plasmid-encoding interleukin-12/human papillomavirus (HPV) DNA plasmids therapeutic vaccine INO-3112 and durvalumab work in treating patients with human papillomavirus associated cancers that have come back or spread to other places in the body. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and durvalumab may work better in treating patients with human papillomavirus associated cancers. | ||||
Detailed Description |
PRIMARY OBJECTIVES: I. To evaluate the anti-tumor activity of DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 (MEDI0457) in combination with durvalumab. SECONDARY OBJECTIVES: I. To determine the safety profile of MEDI0457 in combination with durvalumab in patients with recurrent/metastatic human papilloma virus (HPV) 16- or 18- associated cancer. II. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients with recurrent/metastatic incurable HPV-16/18 positive solid malignancies receiving the combination of MEDI0457and durvalumab. III. To evaluate objective response rate (ORR) by immune-related criteria of the combination of MEDI0457 and durvalumab in patients with recurrent/metastatic incurable HPV-16/18 positive solid malignancies. IV. To evaluate the disease control rate at 24 weeks. EXPLORATORY OBJECTIVES: I. To determine the cellular and humoral immune response to immunotherapy with MEDI0457 in combination with durvalumab, II. To examine the correlation between anti tumor activity and biomarkers including: IIa. HPV-specific cellular and humoral responses. IIb. Programmed death ligand 1 status. IIc. The number of tumor infiltrating lymphocytes, HPV 16/18 E6/E7 deoxyribonucleic acid (DNA) levels and HPV 16/18 E6/E7 DNA sequence in biopsy tissue and plasma. III. To evaluate the pharmacokinetics and anti-drug antibodies (ADA) for durvalumab. OUTLINE: Patients receive DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 intramuscularly (IM) and via electroporation at 1, 3, 7, and 12 weeks and durvalumab intravenously (IV) at 4, 8, and 12 weeks. Starting week 12, cycles repeat every 8 weeks for DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and every 4 weeks for up to 13 doses of durvalumab in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 90 days, every 3 months for 12 months, and then every 6 months thereafter. |
||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||
Condition ICMJE |
|
||||
Intervention ICMJE |
|
||||
Study Arms ICMJE | Experimental: Treatment (INO-3112, durvalumab)
Patients receive DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 IM and via electroporation at 1, 3, 7, and 12 weeks and durvalumab IV at 4, 8, and 12 weeks. Starting week 12, cycles repeat every 8 weeks for DNA plasmid-encoding interleukin-12/HPV DNA plasmids therapeutic vaccine INO-3112 and every 4 weeks for up to 13 doses of durvalumab in the absence of disease progression or unacceptable toxicity.
Interventions:
|
||||
Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
77 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | December 31, 2022 | ||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||
Sex/Gender ICMJE |
|
||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
|
||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03439085 | ||||
Other Study ID Numbers ICMJE | 2017-0302 NCI-2018-00914 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2017-0302 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
|
||||
IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | M.D. Anderson Cancer Center | ||||
Study Sponsor ICMJE | M.D. Anderson Cancer Center | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
|
||||
PRS Account | M.D. Anderson Cancer Center | ||||
Verification Date | December 2020 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |