Metastatic Colorectal CancerPhase 2NCT04475159
Combined Neoadjuvant Systemic and PIPAC Therapy (NASPIT) for Patients With Colorectal Peritoneal Metastasis Eligible for CRS and HIPEC: A Prospective Phase II Trial
A Phase 2 study testing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in people with Metastatic Colorectal Cancer and Peritoneal Carcinomatosis, run by Prof. Aviram Nissan.
Trial summary
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug-delivery system developed to deliver, effectively and safely, small doses of cytotoxic agents into peritoneal tumor deposits. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, Peritoneal Carcinomatosis, Colon Adenocarcinoma
- What is being tested?
- Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2020to 1 Aug 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study and must be willing to return for follow-up
- 18 years of age or older.
- Biopsy (histopathology or cytology) diagnosis of colorectal cancer as defined by the WHO or by cross-sectional imaging reviewed by a board-certified radiologist.
- Good performance status (ECOG < 2), Karnofski >60.
- Patients with low or acceptable surgical risk (American Society of Anesthesiology (ASA) score of 3 or less.
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- Patient is a candidate for CRS and HIPEC as discussed and recommended by the institutional disease management team (DMT, Tumor Board)
- Patient receiving systemic chemotherapy for up to a maximum of 6 months from peritoneal diagnosis management with stable or responsive disease are eligible for the trial.
- Absolute neutrophil count (ANC) exceeds 1200/mm3, white blood cell count exceeds 4000/mm3 and platelet count is greater than 100,000/mm3
- An international normalized ratio (INR) ≤ 1.5 (patients who are therapeutically anticoagulated for non-related medical conditions such as atrial fibrillation and whose anti-thrombotic treatment can be withheld for operation will be eligible
- Adequate hepatic function must be met as evidenced by total serum bilirubin ≤ 1.5 mg/dl (patients with total bilirubin > 1.5 mg/dL eligible only with Gilbert's syndrome); alkaline phosphatase < 2.5 times the upper limit of normal; and, AST less than 1.5 times upper limit of normal [alkaline phosphatase and AST cannot both exceed the upper limit of normal
- Serum renal functional parameters, BUN and creatinine are within normal limits
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening or with negative pregnancy test at screening.
- Life expectancy of at least six months
Who cannot join
- Patients with unresectable (not eligible for CRS/HIPEC) tumors as decided by a multidisciplinary disease management team
- Patients that already received multiple cycles of systemic chemotherapy of more than 6 months and or show progression of disease on systemic therapy.
- Patients with extraperitoneal disease.
- Pregnancy or lactation
- Patients with low performance status (ECOG > 2 or Karnofski < 60%)
- Any one or more of the following hematological abnormalities
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- Hgb < 8gm/dl unable to be corrected with transfusion
- Absolute Neutrophil Count < 1200/mm3
- White blood cell count < 4000/mm3
- Platelet count < 100,000/mm3
- INR > 1.5 (except in patients who are therapeutically AST anticoagulated for non-related medical conditions such as atrial fibrillation and whose anti-thrombotic treatment cannot be withheld for operation will be eligible)
- History of hepatic cirrhosis or present hepatic dysfunction
- Alkaline phosphatase ≥ 2.5 times the upper limit of normal
- ≥ 1.5 times upper limit of normal
- Serum bilirubin > 1.5 mg/dl (except for patients with Gilbert's syndrome who must have direct bilirubin ≤ 1.0 mg/dl)
- Alkaline phosphatase and AST both exceed the upper limit of normal
Trial locations and contacts
No sites are listed yet.
About this study
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug-delivery system developed to deliver, effectively and safely, small doses of cytotoxic agents into peritoneal tumor deposits. It is currently used for palliation and for down-staging of patients who are non-eligible for cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC).
The aim of this study is to evaluate the efficacy of PIPAC used in neoadjuvant setting to enhance the response of patients with colorectal peritoneal metastasis when combined with neoadjuvant systemic therapy for patients eligible to CRS/HIPEC prior to planned surgery.
Read the detailed description
This is an open label, single arm, single center, phase II trial to study the added efficacy benefit of PIPAC administered in the neoadjuvant setting in combination with systemic therapy for patients eligible for CRS/HIPEC.
the following procedures will be done to all study population. Visit 0 (Week #0) screening - Clinical evaluation and baseline cross-sectional imaging. Patients will be evaluated for their eligibility and recruited if found suitable.
(Week #1) tumor board discussion to ensure eligibility and staging (Week #2-4) Initiation of systemic therapy, if not been already started (2 cycles): Systemic therapy will be administered and tailored by the treating oncologist as per patient tolerability. If already on chemotherapy at visit 0, patients will continue chemotherapy until first PIPAC.
Visit 1 (Week #4) first PIPAC: Diagnostic laparoscopy, staging, PCI evaluation and biopsies will be taken as described earlier.
Systemic therapy (2 cycles, Week #4-8): Systemic therapy will be administered and tailored by the treating oncologist as per patient tolerability.
Visit 2 (Week #6) - post first PIPAC - Surgical Oncology Clinic: evaluation of PIPAC tolerability and possible side effects or complications. Cross sectional imaging to monitor progression prior to the upcoming second PIPAC.
Visit 3 (Week #8) - second PIPAC: Diagnostic laparoscopy, staging, PCI evaluation and biopsies will be taken as described earlier.
Systemic therapy (2 cycles, Week #8-12): Systemic therapy will be administered and tailored by the treating oncologist as per patient tolerability. Systemic therapy will be stopped at week#12 (2-4 weeks) prior to planned CRS/HIPEC Visit 4 (Week #10) - post second PIPAC - Surgical Oncology Clinic: evaluation of PIPAC tolerability, quality of life, and possible side effects or complications after PIPAC.
Visit 5 (Week #12-14) - Surgical evaluation and cross-sectional imaging - Surgical Oncology Clinic: Planning for upcoming CRS/HIPEC Visit 6 (Week #14-16) - CRS/HIPEC: proper PCI evaluation, complete tumor cytoreduction and HIPEC will be targeted. The extent of surgery, technical difficulties including OR time and blood loss will be documented.
Visit 7 follow up visit: will be conducted within 1 month after hospital discharge. Tolerability and possible complications post-surgery will be evaluated.
Visit 8-11 follow up visits: Surgical Oncology Clinic evaluation: cross sectional imaging, Tumor markers and clinical evaluation will be conducted for any signs of possible recurrence on 3 monthly bases Visit 12-13 follow up: Surgical oncology clinic: cross sectional imaging, Tumor markers and clinical evaluation will be conducted for any signs of possible recurrence on 6 monthly bases. The follow up for the trial will be concluded at this stage (total of 3 years follow up).
To be noted that patient systemic chemotherapy would not be interrupted throughout the treatment protocol and PIPAC therapy will be delivered in-between chemotherapy cycles.
- Being tested
- Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)
- Medical subject headings
- Colorectal Neoplasms, Peritoneal Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)Procedure or surgery
Pressurized Intraperitoneal Aerosol Chemotherapy will be delivered to the abdominal cavity by means of laparoscopy.
| Study group | Role | What they receive |
|---|---|---|
| PIPAC arm | Experimental | Together with neoadjuvant systemic therpay PIPAC will be performed twice and regional chemotherpay will be administered before planned CRS/HIPEC Receives: Procedure: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Overall Response Rates (BORR)
Clinically, at time of laparoscopic exploration, tumor burden and distribution will be assessed. Peritoneal cancer index (PCI) will be documented. Final evaluation of tumor burden, PCI and clinical response will be evaluated at time of CRS/HIPEC. Radiologically, a baseline abdominal computed tomography (CT) scan will be acquired <4 weeks before the initiation of the treatment plan and will be repeated before CRS/HIPEC. Response will be evaluated by an independent radiologist as per RECIST criteria 1.1. Pathologically, biopsies from representative lesions will be taken. During the first procedure, before PIPAC delivery one sample from each abdominal quadrant and will be submitted to histopathology examination. Each biopsy site will be marked by a sliver clip for subsequent biopsies in the following PIPAC. Final pathological assessment will be done from specimens obtained at time of cytoreductive surgery .
Measured: 12 months after last patient recruitment
Secondary outcomes (1)
Recurrence free survival (RFS)
Recurrence free survival (RFS) will be calculated from the date of CRS/HIPEC to the date of documented disease recurrence. Events for the RFS endpoint include clinical, radiological (CT, PET), serological (CEA, CA-19-9, CA-125) and/or surgical exploration.
Measured: 3 years after the end of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2020
- Study start1 Aug 2020 (estimated)
- Primary completion1 Aug 2022 (estimated)
- Study completion1 Aug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Prof. Aviram Nissan
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Prof. Aviram Nissan, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04475159
- Sponsor's protocol ID
- 6881-20-SMC
- Status last verified
- Jul 2020
- First submitted
- 14 Jul 2020
- Last updated
- 17 Jul 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Neoadjuvant Systemic and PIPAC Therapy (NASPIT) for Patients With Colorectal Peritoneal Metastasis Eligible for CRS and HIPEC: A Prospective Phase II Trial
- ClinicalTrials.gov ID
- NCT04475159
- Acronym / sponsor ID
- 6881-20-SMC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Prof. Aviram NissanOther government
- Study start
- 1 Aug 2020 (estimated)
- Primary completion
- 1 Aug 2022 (estimated)
- Study completion
- 1 Aug 2023 (estimated)
- First posted
- 17 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug-delivery system developed to deliver, effectively and safely, small doses of cytotoxic agents into peritoneal tumor deposits. It is currently used for palliation and for down-staging of patients who are non-eligible for cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC).
The aim of this study is to evaluate the efficacy of PIPAC used in neoadjuvant setting to enhance the response of patients with colorectal peritoneal metastasis when combined with neoadjuvant systemic therapy for patients eligible to CRS/HIPEC prior to planned surgery.
Detailed description
This is an open label, single arm, single center, phase II trial to study the added efficacy benefit of PIPAC administered in the neoadjuvant setting in combination with systemic therapy for patients eligible for CRS/HIPEC.
the following procedures will be done to all study population. Visit 0 (Week #0) screening - Clinical evaluation and baseline cross-sectional imaging. Patients will be evaluated for their eligibility and recruited if found suitable.
(Week #1) tumor board discussion to ensure eligibility and staging (Week #2-4) Initiation of systemic therapy, if not been already started (2 cycles): Systemic therapy will be administered and tailored by the treating oncologist as per patient tolerability. If already on chemotherapy at visit 0, patients will continue chemotherapy until first PIPAC.
Visit 1 (Week #4) first PIPAC: Diagnostic laparoscopy, staging, PCI evaluation and biopsies will be taken as described earlier.
Systemic therapy (2 cycles, Week #4-8): Systemic therapy will be administered and tailored by the treating oncologist as per patient tolerability.
Visit 2 (Week #6) - post first PIPAC - Surgical Oncology Clinic: evaluation of PIPAC tolerability and possible side effects or complications. Cross sectional imaging to monitor progression prior to the upcoming second PIPAC.
Visit 3 (Week #8) - second PIPAC: Diagnostic laparoscopy, staging, PCI evaluation and biopsies will be taken as described earlier.
Systemic therapy (2 cycles, Week #8-12): Systemic therapy will be administered and tailored by the treating oncologist as per patient tolerability. Systemic therapy will be stopped at week#12 (2-4 weeks) prior to planned CRS/HIPEC Visit 4 (Week #10) - post second PIPAC - Surgical Oncology Clinic: evaluation of PIPAC tolerability, quality of life, and possible side effects or complications after PIPAC.
Visit 5 (Week #12-14) - Surgical evaluation and cross-sectional imaging - Surgical Oncology Clinic: Planning for upcoming CRS/HIPEC Visit 6 (Week #14-16) - CRS/HIPEC: proper PCI evaluation, complete tumor cytoreduction and HIPEC will be targeted. The extent of surgery, technical difficulties including OR time and blood loss will be documented.
Visit 7 follow up visit: will be conducted within 1 month after hospital discharge. Tolerability and possible complications post-surgery will be evaluated.
Visit 8-11 follow up visits: Surgical Oncology Clinic evaluation: cross sectional imaging, Tumor markers and clinical evaluation will be conducted for any signs of possible recurrence on 3 monthly bases Visit 12-13 follow up: Surgical oncology clinic: cross sectional imaging, Tumor markers and clinical evaluation will be conducted for any signs of possible recurrence on 6 monthly bases. The follow up for the trial will be concluded at this stage (total of 3 years follow up).
To be noted that patient systemic chemotherapy would not be interrupted throughout the treatment protocol and PIPAC therapy will be delivered in-between chemotherapy cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PIPAC arm | Experimental | Procedure: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)Together with neoadjuvant systemic therpay PIPAC will be performed twice and regional chemotherpay will be administered before planned CRS/HIPEC |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study and must be willing to return for follow-up
- 18 years of age or older.
- Biopsy (histopathology or cytology) diagnosis of colorectal cancer as defined by the WHO or by cross-sectional imaging reviewed by a board-certified radiologist.
- Good performance status (ECOG < 2), Karnofski >60.
Key exclusion criteria (16 listed)
- Patients with unresectable (not eligible for CRS/HIPEC) tumors as decided by a multidisciplinary disease management team
- Patients that already received multiple cycles of systemic chemotherapy of more than 6 months and or show progression of disease on systemic therapy.
- Patients with extraperitoneal disease.
- Pregnancy or lactation
- Patients with low performance status (ECOG > 2 or Karnofski < 60%)
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 |
|---|---|---|
| Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)Pressurized Intraperitoneal Aerosol Chemotherapy will be delivered to the abdominal cavity by means of laparoscopy. | Procedure or surgery | PIPAC arm |
Primary outcome
Best Overall Response Rates (BORR)
Time frame: 12 months after last patient recruitment
Clinically, at time of laparoscopic exploration, tumor burden and distribution will be assessed. Peritoneal cancer index (PCI) will be documented. Final evaluation of tumor burden, PCI and clinical response will be evaluated at time of CRS/HIPEC. Radiologically, a baseline abdominal computed tomography (CT) scan will be acquired <4 weeks before the initiation of the treatment plan and will be repeated before CRS/HIPEC. Response will be evaluated by an independent radiologist as per RECIST criteria 1.1. Pathologically, biopsies from representative lesions will be taken. During the first procedure, before PIPAC delivery one sample from each abdominal quadrant and will be submitted to histopathology examination. Each biopsy site will be marked by a sliver clip for subsequent biopsies in the following PIPAC. Final pathological assessment will be done from specimens obtained at time of cytoreductive surgery .
1 secondary outcome
Recurrence free survival (RFS)
Time frame: 3 years after the end of the trial
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2020.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in people with Metastatic Colorectal Cancer and Peritoneal Carcinomatosis, run by Prof. Aviram Nissan.
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 14 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 17 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gal Levi, M.Sc (972-3-5307595, gal.levi@sheba.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best Overall Response Rates (BORR) (time frame: 12 months after last patient recruitment). 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 17 Jul 2020.