Colorectal CancerPhase 1/2NCT02963831
A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
A Phase 1/2 study testing ONCOS-102, Durvalumab and Cyclophosphamide in people with Colorectal Cancer and Ovarian Cancer, run by Ludwig Institute for Cancer Research at 6 sites in United States.
Trial summary
This is a two-part Phase 1/2 dose escalation and dose expansion study of an Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus), ONCOS-102, in combination with anti-programmed death ligand-1 (PD-L1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Ovarian Cancer, Appendiceal Cancer
- What is being tested?
- ONCOS-102, Durvalumab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 6 sitesUnited States
- Study dates
- 7 Sep 2017to 25 Jun 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with peritoneal disease who have failed prior standard chemotherapy and have histologic confirmation of epithelial ovarian cancer or metastatic colorectal cancer (CRC) including cancer originating from the appendix.
- Subject is willing to undergo a core needle biopsy during screening and Cycle 2, Study Week 5. Archival tumor samples are requested but are not required for eligibility.
- Previously treated for advanced cancer with no additional therapy options available known to prolong survival.
- Laboratory parameters for vital functions should be in the normal range or not clinically significant.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Who cannot join
- Treatment with an investigational agent within 4 weeks of starting study treatment or prior treatment with a checkpoint inhibitor (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], programmed cell death protein 1 [PD-1] or programmed death ligand 1 [PD-L1] antibodies).
- Subject has known active central nervous system metastasis, glioma and nervous system malignancies including carcinomatous meningitis. Subjects with asymptomatic brain metastases or spinal cord compression who have been treated, are considered stable, and who have not received corticosteroids or anticonvulsants for at least 28 days prior to screening may be included. Subject has other active malignancy.
- Known immunodeficiency or known to have evidence of acute or chronic human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C or other uncontrolled inter-current illnesses.
- Ongoing bowel perforation or presence of bowel fistula or abscess or history of small or large bowel obstruction within 3 months of registration, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
- Subjects with clinically significant cardiovascular disease, history of organ transplant or allogeneic bone marrow transplant, active known or history of autoimmune disease that might recur or major surgery within 28 days prior to the first dose or still recovering from prior surgery.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Research Facility
Buffalo, New York, 14263
Research Facility
Charlottesville, Virginia, 22903
Research Facility
Miami, Florida, 33136
Research Facility
New York, New York, 10065
Research Facility
San Diego, California, 92093-0698
Research Facility
Toledo, Ohio, 43614
About this study
Official title: A Phase 1/2 Dose Escalation Study With Expansion Cohorts to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
This is a two-part Phase 1/2 dose escalation and dose expansion study of an Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus), ONCOS-102, in combination with anti-programmed death ligand-1 (PD-L1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed epithelial ovarian cancer or metastatic colorectal cancer.
Read the detailed description
ONCOS-102 will be administered intraperitoneally (IP) at weekly intervals for 6 weeks.
A bolus dose of 300 mg cyclophosphamide (CPO) will be administered intravenously (IV) 1 to 3 days before the first infusion of ONCOS-102. Durvalumab will be administered by IV infusion once every four weeks (Q4W) for a total of 12 four-week cycles.
Phase 1 of the study is a dose escalation phase, which will use a 3+3 design to evaluate the safety of ONCOS-102 monotherapy before initiation of durvalumab and to identify the recommended combination dose (RCD) of a fixed dose of durvalumab (1500 mg) + ONCOS-102 at 2 dose levels (1 x 10^11 viral particles (VPs) and 3 x 10^11 VPs).
Subjects treated at the RCD of 3 x 10^11 VPs ONCOS-102 will be included in the Phase 2 expansion cohort based on their tumor diagnosis.
Phase 2 of the study is the dose expansion phase, which will further explore the safety and anti-tumor activity for the RCD in 2 expansion cohorts with peritoneal disease:
- Epithelial ovarian cancer
- Metastatic colorectal cancer
Simon's 2-Stage MINIMAX Design will be used in Phase 2 for Expansion Cohorts 1 and 2. In the first stage, 18 subjects will be enrolled in Cohort 1 and 13 subjects in Cohort 2 (including the 6 subjects at the RCD from the dose escalation phase).
If 5 or more subjects in Cohort 1, or one or more subjects in Cohort 2, demonstrate clinical benefit (defined as percentage of subjects who are not in progression at end of Week 24), 15 additional subjects will be enrolled in Stage 2 of Cohort 1, and 14 additional subjects will be enrolled in Stage 2 of Cohort 2.
The primary endpoint is the percentage of subjects who are not in progression at the end of Week 24 as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
- Conditions
- Colorectal Cancer, Ovarian Cancer, Appendiceal Cancer
- Being tested
- ONCOS-102, Durvalumab, Cyclophosphamide
- Keywords
- Oncos-102, Durvalumab, Peritoneal, Cyclophosphamide
- Medical subject headings
- Colorectal Neoplasms, Ovarian Neoplasms, Appendiceal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONCOS-102Biological
Also called Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus)
ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks.
DurvalumabDrug
Also called MEDI4736, Imfinzi®
Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles.
CyclophosphamideDrug
Also called Cytoxan®
A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: ONCOS-102 Dose Escalation | Experimental | ONCOS-102, 1 x 10^11 viral particles (VPs) monotherapy for 6 weeks, followed by durvalumab 1500 mg starting on Day 71.
A bolus dose of 300 mg cyclophosphamide (CPO) was administered intravenously (IV) 1 to 3 days before the first infusion of ONCOS-102.
ONCOS-102 was infused intraperitoneally (IP) in a total volume of 500 mL saline (0.9 mg/mL sodium chloride [NaCl] in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1.
Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose every 4 weeks (Q4W) for 10 cycles, starting on Day 71.
Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. Receives: Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide |
| Cohort B: ONCOS-102 Dose Escalation | Experimental | ONCOS-102, 1 x 10^11 VPs + durvalumab 1500 mg starting on Day 15.
A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.
ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1.
Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15.
Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. Receives: Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide |
| Cohort 1: Epithelial Ovarian Cancer | Experimental | ONCOS-102, 3 x 10^11 VPs + durvalumab 1500 mg starting on Day 15.
A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.
ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1.
Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15.
Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. Receives: Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide |
| Cohort 2: Metastatic Colorectal Cancer | Experimental | ONCOS-102, 3 x 10^11 VPs + durvalumab 1500 mg starting on Day 15.
A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102.
ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1.
Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15.
Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. Receives: Biological: ONCOS-102; Drug: Durvalumab; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Dose Limiting Toxicities (DLTs)
All Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 19.0 and classified by MedDRA system organ class (SOC) and preferred term. The severity of AEs was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. TEAEs are those that occurred or worsened after administration of the first dose of study treatment.
Deaths within the AE Reporting Period included all deaths that occurred during the study treatment period, or up to 90 days after the administration of the last dose of study drug or initiation of a new treatment.
Measured: up to 31 months (90 days after the last dose of study medication).
Progression-free Survival (PFS) at Week 24 as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions were categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.
PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the development of new lesions.
Measured: Up to 24 weeks
Secondary outcomes (6)
Median Progression-free Survival (PFS) as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1) Using Kaplan-Meier Method
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions were categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.
PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the development of new lesions.
Measured: Up to 29 months
Objective Response Rate as Measured by as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1)
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions were categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria.
Measured: Up to 15 months
Progression-free Survival (PFS) at Week 24 as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per irRECIST, measurable lesions were categorized as follows: immune-related complete response (irCR): Complete disappearance of all target lesions; immune-related partial response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); immune-related progressive disease (irPD): ≥ 20% increase from nadir in TMTB; immune-related stable disease (irSD): not meeting above criteria.
PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB.
Measured: Up to 24 Weeks
Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5,7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per irRECIST, measurable lesions were categorized as follows: immune-related complete response (irCR): Complete disappearance of all target lesions; immune-related partial response (irPR): ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); immune-related progressive disease (irPD): ≥ 20% increase from nadir in TMTB; immune-related stable disease (irSD): not meeting above criteria.
PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per irRECIST, irPD is defined as a ≥ 20% increase from nadir in the TMTB.
Measured: Up to 39 months
Objective Response Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per irRECIST, measurable lesions were categorized as follows: immune-related complete response (irCR): Complete disappearance of all target lesions; immune-related partial response (irPR): ≥ 30% decrease from baseline in the total measurable tumor burden (TMTB); immune-related progressive disease (irPD): ≥ 20% increase from nadir in TMTB; immune-related stable disease (irSD): not meeting above criteria.
Measured: Up to 15 months
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
After completion of treatment, all subjects were followed for survival every 6 months up to 3 years following initiation of study treatment or until June 25, 2022 when all post-study follow-up was completed. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up (June 25, 2022 when the last follow-up data was collected or earlier). Subjects lost to follow-up are censored on the date when they were last known to be alive.
Measured: Up to 39 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2016 (estimated)
- Study start7 Sep 2017
- Primary completion25 Jun 2022
- Study completion25 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The Phase 1 cohorts were enrolled sequentially. In Phase 2, the two expansion cohorts are enrolled in parallel.
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research Institute, New York City, MedImmune LLC, Targovax ASA
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02963831
- Sponsor's protocol ID
- LUD2015-008
- Status last verified
- Dec 2022
- First submitted
- 10 Nov 2016
- Last updated
- 22 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Dose Escalation Study With Expansion Cohorts to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
- ClinicalTrials.gov ID
- NCT02963831
- Acronym / sponsor ID
- LUD2015-008
- Conditions
- Colorectal Cancer, Ovarian Cancer, Appendiceal Cancer
- Keywords
- Oncos-102, Durvalumab, Peritoneal, Cyclophosphamide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Cancer Research Institute, New York City, MedImmune LLC, Targovax ASA
- Study start
- 7 Sep 2017 (actual)
- Primary completion
- 25 Jun 2022 (actual)
- Study completion
- 25 Jun 2022 (actual)
- First posted
- 15 Nov 2016 (estimated)
- Results
- Posted 22 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a two-part Phase 1/2 dose escalation and dose expansion study of an Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus), ONCOS-102, in combination with anti-programmed death ligand-1 (PD-L1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed epithelial ovarian cancer or metastatic colorectal cancer.
Detailed description
ONCOS-102 will be administered intraperitoneally (IP) at weekly intervals for 6 weeks.
A bolus dose of 300 mg cyclophosphamide (CPO) will be administered intravenously (IV) 1 to 3 days before the first infusion of ONCOS-102. Durvalumab will be administered by IV infusion once every four weeks (Q4W) for a total of 12 four-week cycles.
Phase 1 of the study is a dose escalation phase, which will use a 3+3 design to evaluate the safety of ONCOS-102 monotherapy before initiation of durvalumab and to identify the recommended combination dose (RCD) of a fixed dose of durvalumab (1500 mg) + ONCOS-102 at 2 dose levels (1 x 10^11 viral particles (VPs) and 3 x 10^11 VPs).
Subjects treated at the RCD of 3 x 10^11 VPs ONCOS-102 will be included in the Phase 2 expansion cohort based on their tumor diagnosis.
Phase 2 of the study is the dose expansion phase, which will further explore the safety and anti-tumor activity for the RCD in 2 expansion cohorts with peritoneal disease:
- Epithelial ovarian cancer
- Metastatic colorectal cancer
Simon's 2-Stage MINIMAX Design will be used in Phase 2 for Expansion Cohorts 1 and 2. In the first stage, 18 subjects will be enrolled in Cohort 1 and 13 subjects in Cohort 2 (including the 6 subjects at the RCD from the dose escalation phase).
If 5 or more subjects in Cohort 1, or one or more subjects in Cohort 2, demonstrate clinical benefit (defined as percentage of subjects who are not in progression at end of Week 24), 15 additional subjects will be enrolled in Stage 2 of Cohort 1, and 14 additional subjects will be enrolled in Stage 2 of Cohort 2.
The primary endpoint is the percentage of subjects who are not in progression at the end of Week 24 as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- The Phase 1 cohorts were enrolled sequentially. In Phase 2, the two expansion cohorts are enrolled in parallel.
| Arm | Type | Receives |
|---|---|---|
| Cohort A: ONCOS-102 Dose Escalation | Experimental | Biological: ONCOS-102, Drug: Durvalumab, Drug: CyclophosphamideONCOS-102, 1 x 10^11 viral particles (VPs) monotherapy for 6 weeks, followed by durvalumab 1500 mg starting on Day 71. A bolus dose of 300 mg cyclophosphamide (CPO) was administered intravenously (IV) 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused intraperitoneally (IP) in a total volume of 500 mL saline (0.9 mg/mL sodium chloride [NaCl] in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose every 4 weeks (Q4W) for 10 cycles, starting on Day 71. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. |
| Cohort B: ONCOS-102 Dose Escalation | Experimental | Biological: ONCOS-102, Drug: Durvalumab, Drug: CyclophosphamideONCOS-102, 1 x 10^11 VPs + durvalumab 1500 mg starting on Day 15. A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. |
| Cohort 1: Epithelial Ovarian Cancer | Experimental | Biological: ONCOS-102, Drug: Durvalumab, Drug: CyclophosphamideONCOS-102, 3 x 10^11 VPs + durvalumab 1500 mg starting on Day 15. A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. |
| Cohort 2: Metastatic Colorectal Cancer | Experimental | Biological: ONCOS-102, Drug: Durvalumab, Drug: CyclophosphamideONCOS-102, 3 x 10^11 VPs + durvalumab 1500 mg starting on Day 15. A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102. ONCOS-102 was infused IP in a total volume of 500 mL saline (0.9 mg/mL NaCl in water for injection) by gravity feed or per institutional procedures for IP infusions. ONCOS-102 was to be administered weekly for a total of 6 weeks, starting on Day 1. Durvalumab was administered as an intravenous (IV) infusion at a fixed dose of 1500 mg in either 0.9% (w/v) saline or dextrose Q4W for 12 cycles, starting on Day 15. Optional durvalumab treatment extension beyond the initial 12-cycle treatment period was allowed for subjects who complete the 12-cycle treatment period with Stable Disease or better. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects with peritoneal disease who have failed prior standard chemotherapy and have histologic confirmation of epithelial ovarian cancer or metastatic colorectal cancer (CRC) including cancer originating from the appendix.
- Subject is willing to undergo a core needle biopsy during screening and Cycle 2, Study Week 5. Archival tumor samples are requested but are not required for eligibility.
- Previously treated for advanced cancer with no additional therapy options available known to prolong survival.
- Laboratory parameters for vital functions should be in the normal range or not clinically significant.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Key exclusion criteria (5 listed)
- Treatment with an investigational agent within 4 weeks of starting study treatment or prior treatment with a checkpoint inhibitor (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], programmed cell death protein 1 [PD-1] or programmed death ligand 1 [PD-L1] antibodies).
- Subject has known active central nervous system metastasis, glioma and nervous system malignancies including carcinomatous meningitis. Subjects with asymptomatic brain metastases or spinal cord compression who have been treated, are considered stable, and who have not received corticosteroids or anticonvulsants for at least 28 days prior to screening may be included. Subject has other active malignancy.
- Known immunodeficiency or known to have evidence of acute or chronic human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C or other uncontrolled inter-current illnesses.
- Ongoing bowel perforation or presence of bowel fistula or abscess or history of small or large bowel obstruction within 3 months of registration, including subjects with palliative gastric drainage catheters. Subjects with palliative diverting ileostomy or colostomy are allowed if they have been symptom-free for more than 3 months.
- Subjects with clinically significant cardiovascular disease, history of organ transplant or allogeneic bone marrow transplant, active known or history of autoimmune disease that might recur or major surgery within 28 days prior to the first dose or still recovering from prior surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONCOS-102Also: Adenovirus Vector (Ad5/3-D24-GMCSF), Expressing GM-CSF (GM-CSF-encoding adenovirus)ONCOS-102 was administered by intraperitoneal infusion at weekly intervals for 6 weeks. | Biological | Cohort 1: Epithelial Ovarian Cancer, Cohort 2: Metastatic Colorectal Cancer, Cohort A: ONCOS-102 Dose Escalation, Cohort B: ONCOS-102 Dose Escalation |
| DurvalumabAlso: MEDI4736, Imfinzi®Durvalumab was administered by IV infusion once every four weeks for a total of 10 (Cohort A) or 12 four-week cycles. | Drug | Cohort 1: Epithelial Ovarian Cancer, Cohort 2: Metastatic Colorectal Cancer, Cohort A: ONCOS-102 Dose Escalation, Cohort B: ONCOS-102 Dose Escalation |
| CyclophosphamideAlso: Cytoxan®A bolus dose of 300 mg cyclophosphamide (CPO) was administered IV 1 to 3 days before the first infusion of ONCOS-102. | Drug | Cohort 1: Epithelial Ovarian Cancer, Cohort 2: Metastatic Colorectal Cancer, Cohort A: ONCOS-102 Dose Escalation, Cohort B: ONCOS-102 Dose Escalation |
Primary outcome
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Dose Limiting Toxicities (DLTs)
Time frame: up to 31 months (90 days after the last dose of study medication).
All Adverse events (AEs) were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 19.0 and classified by MedDRA system organ class (SOC) and preferred term. The severity of AEs was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. TEAEs are those that occurred or worsened after administration of the first dose of study treatment. Deaths within the AE Reporting Period included all deaths that occurred during the study treatment period, or up to 90 days after the administration of the last dose of study drug or initiation of a new treatment.
Progression-free Survival (PFS) at Week 24 as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Up to 24 weeks
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 28 days before the first dose of study treatment), at cycles 3, 5, 7, 9, and 11 during study treatment, and during on-study follow-up starting 8 weeks after the last disease assessment. Per RECIST 1.1, target lesions were categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; PD: ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria. PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression or to the date of death, if disease progression does not occur. Per RECIST 1.1, progressive disease (PD) is defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the development of new lesions.
6 secondary outcomes
Median Progression-free Survival (PFS) as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1) Using Kaplan-Meier Method
Time frame: Up to 29 months
Objective Response Rate as Measured by as Measured by Response Evaluation in Solid Tumors 1.1 (RECIST 1.1)
Time frame: Up to 15 months
Progression-free Survival (PFS) at Week 24 as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time frame: Up to 24 Weeks
Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method
Time frame: Up to 39 months
Objective Response Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time frame: Up to 15 months
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
Time frame: Up to 39 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ONCOS-102, Durvalumab and Cyclophosphamide in people with Colorectal Cancer and Ovarian Cancer, run by Ludwig Institute for Cancer Research at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Dose Limiting Toxicities (DLTs) (time frame: up to 31 months (90 days after the last dose of study medication).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2022.