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PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO) (OBERTO)

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ClinicalTrials.gov Identifier: NCT03391232
Recruitment Status : Recruiting
First Posted : January 5, 2018
Last Update Posted : September 25, 2018
Sponsor:
Collaborators:
Mayo Clinic
University of Pisa
Information provided by (Responsible Party):
Treos Bio Zrt

Brief Summary:
Phase I/II clinical trial investigates the safety, tolerability, immunogenicity and preliminary efficacy of multiple doses of PolyPEPI1018 CRC vaccine as an add-on treatment to the standard-of-care maintenance therapy in patients with metastatic colorectal cancer. Clinical responses will be evaluated by indiction of T cell responses, T lymphocyte infiltration in accessible biopsy sites, and by objective tumor responses. This study will also explore the accuracy of the predicted T cell responses in each patient using the candidate companion diagnostic test and the correlations between clinical responses and predicted T cell responses.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: PolyPEPI1018 CRC Vaccine Phase 1 Phase 2

Detailed Description:

This is a Phase I/II, open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity and efficacy of a multiple subcutaneous injection of PolyPEPI1018 as an add-on immunotherapy to the standard-of-care maintenance therapy in approximately 15 subjects with metastatic colorectal cancer.

The first part of the study investigates the administration of a single vaccine dose during 12‑week follow‑up period on an outpatient basis. Screening is performed in parallel with the subject's completion of the standard-of-care first-line treatment and initiation of the standard-of-care maintenance treatment. A single dose of PolyPEPI1018 is administered after the subject initiates the maintenance regimen, and within 3 weeks after the eligibility CT scan was performed. Subjects are monitored every 3 weeks for 12 weeks.

The second part of the study investigates the administration of 3 vaccine doses (Weeks 0, 13, 26) then 12 weeks follow‑up on an outpatient basis.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Tolerability, Immunogenicity and Efficacy of Multiple PolyPEPI1018 Vaccinations as an Add-on Immunotherapy to the Standard-of-Care Maintenance Therapy in Subjects With Metastatic Colorectal Cancer
Actual Study Start Date : April 9, 2018
Estimated Primary Completion Date : April 9, 2019
Estimated Study Completion Date : December 21, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PolyPEPI1018 CRC Vaccine
The vaccine contains 6 synthetic peptides mixed with the adjuvant Montanide™. The peptides were selected to induce T cell responses against 12 dominant epitopes from 7 cancer testis antigens (CTAs), which are the most frequently expressed CTAs in colorectal cancer. The 6 peptides were optimized to induce long lasting CRC specific T cell responses.
Biological: PolyPEPI1018 CRC Vaccine
Colorectal Cancer Vaccine




Primary Outcome Measures :
  1. Incidence of Treatment Related Adverse Events [ Time Frame: 21 days after each vaccinations ]
    Occurrence of at least 1 ≥Grade 4 local adverse event (AE) or 1 ≥Grade 3 systemic AE and/or signs/symptoms, lab toxicities, and/or clinical events that is probably or definitely related to study treatment


Secondary Outcome Measures :
  1. Prediction of T cell responses [ Time Frame: 21 days ]
    Predict vaccine-induced T cells in each study subject using the candidate CDx

  2. Measure T cell responses [ Time Frame: 12 weeks ]
    To measure vaccine-induce T cell responses in each study subjects


Other Outcome Measures:
  1. Measure objective tumor responses [ Time Frame: 12 weeks ]
    CT scans will be performed at screening and weeks 6,12 after each vaccination



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects, 18-75 years of age at time of Screening who provide written informed consent prior to initiation of any study procedure
  2. Histologically confirmed metastatic adenocarcinoma originating from the colon or the rectum
  3. Presence of at least 1 measurable reference lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
  4. Experienced PR or stable disease during first‑line treatment with a systemic chemotherapy regimen and 1 biological therapy regimen
  5. Maintenance therapy with a fluoropyrimidine (5-fluorouracil or capecitabine) plus the same biologic agent (bevacizumab, cetuximab or panitumumab) used during induction, scheduled to initiate prior to the first day of treatment with the study drug
  6. No more than 1 line of chemotherapy regimen for mCRC (adjuvant therapy for non-metastasized disease is allowed if terminated more than 6 months before Screening and without recurrence within 6 months after the end of adjuvant treatment)
  7. Last CT scan at 3 weeks or less before the first day of treatment
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  9. Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of <1% per year) for 3 months from the day of the treatment. An effective form of contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm, cervical cap or condom
  10. Men must agree to use an effective form of contraception (as defined above), and not donate sperm for 3 months from the day of the treatment
  11. White blood cell count ≥3.0 × 109/L with neutrophils ≥1.5 × 109/L
  12. Platelets ≥100 × 109/L, hemoglobin ≥5.6 mmol/L (corresponding to 9 g/dL)
  13. Serum bilirubin ≤1.5 × upper limit of normal (ULN) set by the site
  14. Alanine amino transferase (ALAT) and aspartate amino transferase (ASAT) ≤2.5 × ULN in the absence of liver metastases. ALAT and ASAT ≤5 × ULN set by the site in the presence of liver metastases
  15. Serum creatinine ≤1.5 × ULN set by the site and creatinine clearance >30 mL/min using Cockroft formula
  16. Relevant toxicities of prior therapies must have resolved, except for oxaliplatin-related neuropathy or alopecia
  17. Anticipated life expectancy ≥6 months Subject is willing and able to comply with the requirements of the protocol

Exclusion Criteria:

  1. Received chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks prior to start of study treatment
  2. Received continuous systemic steroid treatment within the last 2 weeks prior to start of study treatment
  3. Colorectal cancer with documented high microsatellite instability (MSI‑H)
  4. Colorectal cancer with documented BRAF mutations
  5. Pre-existing systemic autoimmune or antibody-mediated diseases or immune deficiency diseases
  6. Central nervous system (CNS) metastases
  7. Active or uncontrolled severe infections or undiagnosed febrile condition >38ºC
  8. Acute or subacute intestinal obstruction or history of chronic intestinal inflammatory diseases
  9. Symptomatic peritoneal carcinomatosis
  10. Peritonitis
  11. Serious, non-healing wounds, ulcers or bone fractures
  12. Nephrotic syndrome
  13. Arterial thromboembolisms or severe hemorrhages within 6 months before study enrolment (except bleeding tumor before tumor resection surgery)
  14. Hemorrhagic diathesis or thrombotic tendency
  15. Major surgery or radiotherapy within 12 weeks prior to the study treatment or anticipation of needing such procedure during the study period
  16. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days
  17. Participants with active malignancy (other than colorectal cancer) or a prior malignancy within the past 12 months
  18. Participant with myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to the first dose of study treatment, any electrocardiogram (ECG) abnormality at Screening must be documented by the investigator as not medically relevant
  19. Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study
  20. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study
  21. Known hypersensitivity to any component of the investigational drug
  22. If female, participant is pregnant (exclusion confirmed with beta-human chorionic gonadotropin [hCG] test) or lactating at the time of enrollment, or has plans to become pregnant or start breastfeeding during the study
  23. Pre-existing alcohol or drug abuse
  24. Medical or mental impairments which make it impossible to obtain the patient's consent or to conduct the study
  25. A significant concomitant medical condition which the clinical investigator believes precludes the patient from enrolling in the study Absent or limited legal competence

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03391232


Contacts
Contact: Franco Lori, MD, PhD +39 347 0723942 franco.lori@treosbio.com
Contact: Julianna Lisziewicz, PhD +12023450011 julianna.lisziewicz@treosbio.com

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Joleen Hubbard, MD    507-405-0312    hubbard.joleen@mayo.edu   
Italy
Universiti di Pisa Recruiting
Pisa, PI, Italy
Contact: Chiara Cremolini, MD    +39 349 78 66 756    chiaracremolini@gmail.com   
Sponsors and Collaborators
Treos Bio Zrt
Mayo Clinic
University of Pisa
Investigators
Study Chair: Lori Franco, MD, PhD Treos Bio Zrt

Additional Information:
Responsible Party: Treos Bio Zrt
ClinicalTrials.gov Identifier: NCT03391232     History of Changes
Other Study ID Numbers: OBERTO 101
First Posted: January 5, 2018    Key Record Dates
Last Update Posted: September 25, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs