Metastatic Colorectal CancerPhase 1PICCASSONCT03274804
Combined PD-1 and CCR5 Inhibition for the Treatment of Refractory Microsatellite Stable mCRC
A Phase 1 study testing Pembrolizumab and Maraviroc in people with Metastatic Colorectal Cancer and MSS, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
This is a monocentric, single arm, prospective, open-label trial of a combination treatment consisting of pembrolizumab and maraviroc in previously treated subjects who have refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, MSS
- What is being tested?
- Pembrolizumab and Maraviroc
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- 1 Apr 2018to 1 Mar 2020
- Phase
- Phase 1
- 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
- Histologically confirmed metastatic colorectal cancer. Microsatellite stability (MSS) is confirmed by PCR or immunohistochemistry.
- Patient failed standard therapy or is intolerable towards standard therapy which must include a fluoropyrimidine, oxaliplatin, irinotecan, an antiangiogenic monoclonal antibody (e.g. bevacizumab, aflibercept, ramucirumab), an EGFR inhibitor in case of RAS/BRAF wildtype tumors and optional regorafenib or TAS 102
- Measurable disease as per RECIST 1.1
- Metastatic lesion accessible for repetitive biopsies and patient willing to provide tissue from newly obtained biopsies. Patients without accessible lesions might be enrolled after discussion with the principle investigator.
- ECOG performance status 0 or 1
- Adequate hematological, hepatic and renal function parameters:
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- Leucocytes> 3.000/μl
- Hemoglobin >9 g/dl
- Thrombocytes > 100.000/μl
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or GFR ≥60 mL/min for subject with creatinine levels > 1.5 x institutional ULN
- Serum total bilirubin ≤ 1.5 x upper limit of normal or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN
- AST and ALT ≤ 2.5 x upper limit of normal (or ≤ 5 x if liver metastases are present)
- Albumin ≥ 2.5 mg/dL
- Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile.
- Female and male patients' ≥ 18 years. Patients in reproductive age must be willing to use adequate contraception during the study and 4 months after the end of the study (appropriate contraception is defined as surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), and doublebarrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)). Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception. Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
- Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures.
Who cannot join
- Inability to understand the aims of the study and/or protocol procedures
- Hypersensitivity towards pembrolizumab, maraviroc, or any ingredients of the formulations administered
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies
- Any other concurrent antineoplastic treatment including irradiation (local radiation of single non-target lesions for palliation only allowed)
- Active autoimmune disease requiring immunosuppressive therapy
- Any condition requiring continuous systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks prior to first dose of study treatment. Inhaled or topical steroids and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
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- Secondary malignant disease during the last 5 years (exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
- Clinical relevant comorbidity also including significant psychiatric disease
- Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, NYHA III-IV
- Cardiocirculatory insufficiency with hypotension (systolic blood pressure <100 mmHg)
- Cirrhosis of the liver (Child > Grade A), pronounced alcohol abuse with anticipated detoxification, severe pulmonary infection with considerable reduction of pulmonary function
- Prior allogeneic bone marrow transplantation
- Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 therapeutic antibody
- Administration of a live, attenuated vaccine within four weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Chronic intake of drugs that lead to known interference with Maraviroc metabolism through strong Cytochrome P450 3A4 (CYP3A4) interaction: e.g. Rifampicin, Rifabutin, Clarithromycin, Telithromycin, Ketoconazole, Itraconazole, Fluconazole, Hypericum perforatum (St. John's Worth /Johanniskraut) or any strong CYP3A4 inducing or inhibiting drug (See Section 5.5.2)
- Positive test for human immunodeficiency virus (HIV) or HIV infection
- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test) or hepatitis C. Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible.
- Active or latent tuberculosis
- Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms.
- Subjects with treated brain metastases that are no longer symptomatic and require no treatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy and have no evidence of disease progression on imaging studies (MRI/CT scan).
- On-treatment participation in another clinical study in the period 30 days prior to start of study treatment and during the study
- Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
- Pregnancy or lactation
- Known history of, or any evidence of active, non-infectious pneumonitis or interstitial lung disease.
- Active infection requiring systemic therapy.
Trial locations and contacts
1 site in 1 country.
Germany1 site
National Center for Tumor Diseases, University Hospital Heidelberg
Heidelberg
About this study
Official title: A Phase I Trial of Combined PD-1 Inhibition (Pembrolizumab) and CCR5 Inhibition (Maraviroc) for the Treatment of Refractory Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
This is a monocentric, single arm, prospective, open-label trial of a combination treatment consisting of pembrolizumab and maraviroc in previously treated subjects who have refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Read the detailed description
Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).
Treatment with pembrolizumab / maraviroc combination will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, administrative reasons requiring cessation of treatment, or completion of treatment per protocol.
Subjects with a treatment response or stable disease after completion of the first treatment phase of eight cycles (core treatment period) will be offered, at the discretion of the investigator, participation in a maintenance phase consisting of up to 24 additional treatment cycles of pembrolizumab monotherapy (total treatment duration up to 24 months).
Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed for overall survival (OS) until death, withdrawal of consent, loss to follow-up, or the end of the study.
After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAEs) and AEs of special interest (AESIs) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.
- Conditions
- Metastatic Colorectal Cancer, MSS
- Being tested
- Pembrolizumab, Maraviroc
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called Keytruda
Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22)
MaravirocDrug
Also called Celsentri
Maraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22)
| Study group | Role | What they receive |
|---|---|---|
| Single arm, prospective, open-label trial | Experimental | Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22). Receives: Biological: Pembrolizumab; Drug: Maraviroc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility Rate of a Combined Therapy
Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events:
Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment
Measured: After core treatment period of 8 cycles (each cycle is 21 days)
Secondary outcomes (5)
Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities
The primary safety analysis will be based on subjects who experienced toxicities as defined by the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, v4.0; Section 11.2). The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications administered will be recorded.
Measured: After core treatment period of 8 cycles (each cycle is 21 days)
Efficacy Endpoint: Disease Control Rate
Determine DCR defined as percentage of patients displaying CR/PR or SD as best response according to the RECIST criteria version 1.1.
Measured: through study completion (20 months)
Efficacy Endpoint: Objective Response Rate
ORR and immune related (ir) ORR (irORR) will be analyzed.
Measured: through study completion (20 months)
Efficacy Endpoint: Progression-free Survival
Individual PFS will be analyzed.
Measured: through study completion (20 months)
Overall Survival
Individual OS will be analyzed.
Measured: through study completion (20 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start1 Apr 2018
- Primary completion1 Mar 2020
- Study completion1 Mar 2020
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Collaborators
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Responsible party
- Principal investigator, Dirk Jäger, University Hospital Heidelberg
- Investigators
- Dirk Jäger, Prof., Principal investigator, NCT, Med Oncology, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03274804
- Sponsor's protocol ID
- PICCASSO
- Acronym
- PICCASSO
- Status last verified
- May 2022
- First submitted
- 14 Aug 2017
- Last updated
- 7 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Haag GM, Springfeld C, Grun B, Apostolidis L, Zschabitz S, Dietrich M, Berger AK, Weber TF, Zoernig I, Schaaf M, Waberer L, Muller DW, Al-Batran SE, Halama N, Jaeger D. Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer - The PICCASSO phase I trial. Eur J Cancer. 2022 May;167:112-122. doi: 10.1016/j.ejca.2022.03.017. Epub 2022 Apr 12.
PubMed 35427833
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Combined PD-1 Inhibition (Pembrolizumab) and CCR5 Inhibition (Maraviroc) for the Treatment of Refractory Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)
- ClinicalTrials.gov ID
- NCT03274804
- Acronym / sponsor ID
- PICCASSO / PICCASSO
- Conditions
- Metastatic Colorectal Cancer, MSS
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Collaborators
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 1 Mar 2020 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 7 Sep 2017 (actual)
- Results
- Posted 22 Apr 2021
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 monocentric, single arm, prospective, open-label trial of a combination treatment consisting of pembrolizumab and maraviroc in previously treated subjects who have refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Detailed description
Eligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22).
Treatment with pembrolizumab / maraviroc combination will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, administrative reasons requiring cessation of treatment, or completion of treatment per protocol.
Subjects with a treatment response or stable disease after completion of the first treatment phase of eight cycles (core treatment period) will be offered, at the discretion of the investigator, participation in a maintenance phase consisting of up to 24 additional treatment cycles of pembrolizumab monotherapy (total treatment duration up to 24 months).
Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed for overall survival (OS) until death, withdrawal of consent, loss to follow-up, or the end of the study.
After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAEs) and AEs of special interest (AESIs) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm, prospective, open-label trial | Experimental | Biological: Pembrolizumab, Drug: MaravirocEligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) together with maraviroc administered perorally on day 1 to 21 of each cycle (d1-21; qd22). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically confirmed metastatic colorectal cancer. Microsatellite stability (MSS) is confirmed by PCR or immunohistochemistry.
- Patient failed standard therapy or is intolerable towards standard therapy which must include a fluoropyrimidine, oxaliplatin, irinotecan, an antiangiogenic monoclonal antibody (e.g. bevacizumab, aflibercept, ramucirumab), an EGFR inhibitor in case of RAS/BRAF wildtype tumors and optional regorafenib or TAS 102
- Measurable disease as per RECIST 1.1
- Metastatic lesion accessible for repetitive biopsies and patient willing to provide tissue from newly obtained biopsies. Patients without accessible lesions might be enrolled after discussion with the principle investigator.
- ECOG performance status 0 or 1
Key exclusion criteria (25 listed)
- Inability to understand the aims of the study and/or protocol procedures
- Hypersensitivity towards pembrolizumab, maraviroc, or any ingredients of the formulations administered
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies
- Any other concurrent antineoplastic treatment including irradiation (local radiation of single non-target lesions for palliation only allowed)
- Active autoimmune disease requiring immunosuppressive therapy
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 |
|---|---|---|
| PembrolizumabAlso: KeytrudaEligible subjects will receive pembrolizumab beginning on Day 1 of each 3-week dosing cycle (d1, qd22) | Biological | Single arm, prospective, open-label trial |
| MaravirocAlso: CelsentriMaraviroc will be administered perorally on day 1 to 21 of each cycle (d1-21; qd22) | Drug | Single arm, prospective, open-label trial |
Primary outcome
Feasibility Rate of a Combined Therapy
Time frame: After core treatment period of 8 cycles (each cycle is 21 days)
Defined as the rate of patients receiving the protocol treatment according to the planned schedule without occurrence of at least one of the following events: Study treatment-related Grade ≥ 3 immune-related abnormalities; Study treatment-related Grade ≥ 4 AEs of any aetiology; Any toxic event leading to the premature withdrawal of protocol treatment
5 secondary outcomes
Safety and Toxicity of a Combined Therapy Based on Subjects Who Experienced Toxicities
Time frame: After core treatment period of 8 cycles (each cycle is 21 days)
Efficacy Endpoint: Disease Control Rate
Time frame: through study completion (20 months)
Efficacy Endpoint: Objective Response Rate
Time frame: through study completion (20 months)
Efficacy Endpoint: Progression-free Survival
Time frame: through study completion (20 months)
Overall Survival
Time frame: through study completion (20 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35427833Haag GM, Springfeld C, Grun B, Apostolidis L, Zschabitz S, Dietrich M, Berger AK, Weber TF, Zoernig I, Schaaf M, Waberer L, Muller DW, Al-Batran SE, Halama N, Jaeger D. Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer - The PICCASSO phase I trial. Eur J Cancer. 2022 May;167:112-122. doi: 10.1016/j.ejca.2022.03.017. Epub 2022 Apr 12.
- 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.
Dirk Jäger, Prof. principal investigator
NCT, Med Oncology, University Hospital Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab and Maraviroc in people with Metastatic Colorectal Cancer and MSS, run by University Hospital Heidelberg at 1 site in Germany.
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 16 inclusion and 25 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 7 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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 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.
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 Apr 2021). 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?
Feasibility Rate of a Combined Therapy (time frame: After core treatment period of 8 cycles (each cycle is 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03274804, which also lists 1 linked publication.
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 7 Jun 2022.