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A Phase 1/2 Study to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies

NCT02963831

Description:

This is a two-part Phase 1/2 dose escalation and dose expansion study of the GMCSF-encoding adenovirus, ONCOS-102, in combination with anti-programmed death ligand-1 (PDL1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed platinum-resistant or refractory epithelial ovarian cancer or colorectal cancer.

Related Conditions:
  • Appendix Carcinoma
  • Colorectal Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1/2 Study to Investigate the Safety, Biologic and Anti-tumor Activity of ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies
  • 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

Clinical Trial IDs

  • ORG STUDY ID: LUD2015-008
  • NCT ID: NCT02963831

Conditions

  • Colorectal Cancer
  • Platinum-resistant Ovarian Cancer
  • Appendiceal Cancer

Interventions

DrugSynonymsArms
ONCOS-102Dose Escalation
DurvalumabMEDI4736Dose Escalation

Purpose

This is a two-part Phase 1/2 dose escalation and dose expansion study of the GMCSF-encoding adenovirus, ONCOS-102, in combination with anti-programmed death ligand-1 (PDL1) antibody, durvalumab, in adult subjects with peritoneal disease who have failed prior standard chemotherapy and have histologically confirmed platinum-resistant or refractory epithelial ovarian cancer or colorectal cancer.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalDuring Phase 1 of the study, subjects will be evaluated for DLTs before proceeding to a subsequent cohort. Dose escalation for the determination of RCD will be performed based on the available dose levels and the respective rules for a standard 3 + 3 dose escalation study design. For Cohort A, ONCOS-102 will be given as monotherapy the first six weeks, and then durvalumab (1500 mg) will be starting on day 71. For Cohorts B and C, ONCOS-102 will be administered for a total of 6 weeks while durvalumab will be given for a total of 12 four-week cycles.
  • ONCOS-102
  • Durvalumab
Cohort 1: Platinum-resistant epithelial ovarian cancerExperimentalONCOS-102 will be administered for a total of 6 weeks, while durvalumab will be administered for a total of 12 cycles, starting on Day 15.
  • ONCOS-102
  • Durvalumab
Cohort 2: Colorectal cancerExperimentalONCOS-102 will be administered for a total of 6 weeks, while durvalumab will be administered for a total of 12 cycles, starting on Day 15.
  • ONCOS-102
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. Previously treated for advanced cancer with no additional therapy options available
             known to prolong survival.

          4. Laboratory parameters for vital functions should be in the normal range or not
             clinically significant.

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

        Exclusion Criteria:

          1. 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).

          2. 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.

          3. Known immunodeficiency or known to have evidence of acute or chronic or human
             immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C or other uncontrolled
             inter-current illnesses.

          4. 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.

          5. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Adverse Events
Time Frame:up to 15 months
Safety Issue:
Description:Clinical laboratory tests, vital sign and weight measurements, physical exams, performance status evaluation, imaging scans and any other medically indicated assessments, including subject interviews, will be performed to detect new abnormalities and deteriorations of any pre-existing conditions. The investigator will evaluate any laboratory abnormalities for clinical significance, and clinically significant abnormalities will be recorded as adverse events. All clinically significant abnormalities and deteriorations from time of signing the informed consent to the end of study visit will be recorded in the Case Report Forms as adverse events and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

Secondary Outcome Measures

Measure:Clinical Benefit (Complete Response, Partial Response and Stable Disease)
Time Frame:up to 24 weeks
Safety Issue:
Description:Clinical Benefit is defined as percentage of subjects who are in the study and not in progression at the end of Week 24.
Measure:Objective Response Rate
Time Frame:up to 15 months
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:Up to 15 months
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:up to 4 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ludwig Institute for Cancer Research

Trial Keywords

  • Oncos-102
  • Durvalumab
  • Peritoneal
  • Cyclophosphamide

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