Metastatic Colorectal CancerPhase 2RESCUENCT03418558
Study of Trastuzumab-emtansine in Patients With HER2-positive Metastatic Colorectal Cancer Progressing After Trastuzumab and Lapatinib.
A Phase 2 study testing Trastuzumab emtansine in people with Metastatic Colorectal Cancer, run by Fondazione del Piemonte per l'Oncologia at 3 sites in Italy.
Trial summary
This is a phase II, open label, multicenter study. Patients with advanced colon rectal cancer (CRC) harboring an amplified HER2 that have been previously treated and progressed with an aNti-HER2 treatment, will be treated with the anti HER2 antibody conjugate trastuzumab emtansine (TDM1). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Trastuzumab emtansine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 3 sitesItaly
- Study dates
- 8 Jul 2015to Jun 2019
- 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
- Histological/confirmed adenocarcinoma of the colon or rectum with metastatic disease not amenable to salvage surgery.
- Progression (PD) during or after therapy with anti-HER2 therapy including those in HERACLES trial cohort A (trastuzumab and lapatinib) within the HERACLES - A trial.
- ECOG PS < 2
- Measurable disease as defined by RECIST 1.1 criteria
- Adequate hematological function as defined by: ANC >= 1.5 x 10^9/L, platelet count >=100 x 10^9/L, hemoglobin >= 10 g/dL.
- Adequate renal function, as defined by: creatinine >= 1.5 x UNL
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- Adequate hepatobiliary function, as defined by the following baseline liver function tests:
- total serum bilirubin >=1.5 upper normal limit (UNL) (unless documented Gilbert's syndrome )
- alanine aminotransferase (ALT), aspartate aminotransferase (AST) >= 2.5xUNL
- alkaline phosphatase (AP) >= 2.5xUNL; if total alkaline phosphatase (AP) > 2.5xUNL, alkaline phosphatase liver fraction must be >= 2.5xUNL
- Adequate contraception for all fertile patients
- Negative pregnancy test.
Who cannot join
- Symptomatic brain metastases
- Active infection
- Interval from last anti HER2 therapy < 2 weeks. Patients in treatment with T-DM1 (provided by third-parties) may be eligible for immediate treatment if not in progression at the time of protocol entry.
- Prior chemotherapy <4 weeks.
- Impaired cardiac function including any of the following: uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; chronic heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication, baseline Left Ventricular Ejection Fraction (LVEF) ≤ 55% measured by echocardiography (ECHO)
- Major surgery in the two weeks prior to entering the clinical trial
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- Concurrent treatment with any other anti-cancer therapy
- Patient unable to comply with the study protocol owing to psychological, social or geographical reasons
- Pregnant and lactating women
- Men and women of childbearing potential who are not using an effective method of contraception
- Participation in another clinical trial
- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
Trial locations and contacts
3 sites in 1 country.
Italy3 sites, 1 recruiting
- Completed
Fondazione del Piemonte per l'Oncologia
Candiolo, 10060
- Recruiting
Grande Ospedale Metropolitano Niguarda
Milan
Salvatore Siena, MD, salvatore.siena@ospedaleniguarda.it
- Completed
IOV - Istituto Oncologico Veneto
Padova
About this study
Official title: Open-label, Phase II Study of Trastuzumab Emtansine in Patients With HER2-positive Metastatic Colorectal Cancer Progressing After Trastuzumab and Lapatinib: HERACLES RESCUE. (HER2 Amplification for Colo-rectaL Cancer Enhanced Stratification - REchallenge With her2 Selective Cytotoxic Uptake of Emtansine)
This is a phase II, open label, multicenter study. Patients with advanced colon rectal cancer (CRC) harboring an amplified HER2 that have been previously treated and progressed with an aNti-HER2 treatment, will be treated with the anti HER2 antibody conjugate trastuzumab emtansine (TDM1).
Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death. Main objective of the study is the evaluation of objective response rate according to RECIST 1.1 criteria. Disease control rate, defined as the sum of complete, partial and stable disease patients over total patient, followed by response duration, time to progression and safety are secondary endpoints.
Read the detailed description
In metastatic colorectal cancer, HER2 amplified patients relapsing after initial long-lasting response to the anti HER combination of trastuzumab + lapatinib, HER2 gene amplification, and the ensuing high levels of HER2 expression on the tumor surface, persist in spite of the tumor progression as determined by HER2 amplified ctDNA levels measured at progression and HER2 IHC findings on rebiopsies of resistant tumors. These findings offer an unexpected 'precision chemotherapy' rescue potential, in spite of progression under anti HER2 treatment and were confirmed experimentally in a HER2 amplified mCRC PDX (metastatic ColoRectal Carcinoma Patient Derived Xenografts), model generated from the viable biopsy of a relapsing HERACLES patient. In this model a randomized trial comparing TDM1 to pertuzumab versus control (6 animal per arm), showed that T-DM1, but not pertuzumab treated animals achieved tumor disappearance. The results of this experiment confirm the principle strength of targeted toxins which is based on their bipartite structure, with one component binding to a disease-specific cell-surface target molecule and the other conferring cytotoxicity, once internalized. In this case HER2 amplification confer to the tumor the characteristics of a 'molecular sponge' for TDM1 with the trastuzumab moiety targeting the still over-abundant HER2 bound to the cell-surface of anti HER2 resistant tumor cell clusters, thus allowing for a 'surgical' delivery of the emtansine cytotoxicity moiety. Given the good predictability of mCRC PDXs model, as testified by HERACLES TRIAL results (NCT03225937), investigators believe that this activity signal should be tested in the clinic. It is therefore proposed a proof-of-concept trial of T-DM1 in HER2 amplified mCRC patients progressing or relapsing after trastuzumab-lapatinib treatment.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Trastuzumab emtansine
- Keywords
- HER2 AMPLIFICATION
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab emtansineDrug
| Study group | Role | What they receive |
|---|---|---|
| HERACLES RESCUE | Experimental | Patients will receive trastuzumab-emtansine, iv 3,6 mg/kg every 21 days. Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever come first Receives: Drug: Trastuzumab emtansine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate according to RECIST 1.1 criteria
Measured: every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months
Secondary outcomes (2)
Description of the frequency and severity of Adverse Events based on the NCI -CTCAE V4.0
Measured: every 21 days from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months
Progression Free Survival
Progression Free Survival
Measured: every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2018
- Study start8 Jul 2015
- Primary completionJun 2019 (estimated)
- Study completionJun 2019 (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
- 13 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione del Piemonte per l'Oncologia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03418558
- Sponsor's protocol ID
- 011-IRCC-10IIS-15
- Acronym
- RESCUE
- Status last verified
- Oct 2018
- First submitted
- 24 Jan 2018
- Last updated
- 31 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Phase II Study of Trastuzumab Emtansine in Patients With HER2-positive Metastatic Colorectal Cancer Progressing After Trastuzumab and Lapatinib: HERACLES RESCUE. (HER2 Amplification for Colo-rectaL Cancer Enhanced Stratification - REchallenge With her2 Selective Cytotoxic Uptake of Emtansine)
- ClinicalTrials.gov ID
- NCT03418558
- Acronym / sponsor ID
- RESCUE / 011-IRCC-10IIS-15
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- HER2 AMPLIFICATION
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 13 participants (estimated)
- Lead sponsor
- Fondazione del Piemonte per l'OncologiaUniversity, hospital or other
- Study start
- 8 Jul 2015 (actual)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Jun 2019 (estimated)
- First posted
- 1 Feb 2018 (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.
This is a phase II, open label, multicenter study. Patients with advanced colon rectal cancer (CRC) harboring an amplified HER2 that have been previously treated and progressed with an aNti-HER2 treatment, will be treated with the anti HER2 antibody conjugate trastuzumab emtansine (TDM1).
Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death. Main objective of the study is the evaluation of objective response rate according to RECIST 1.1 criteria. Disease control rate, defined as the sum of complete, partial and stable disease patients over total patient, followed by response duration, time to progression and safety are secondary endpoints.
Detailed description
In metastatic colorectal cancer, HER2 amplified patients relapsing after initial long-lasting response to the anti HER combination of trastuzumab + lapatinib, HER2 gene amplification, and the ensuing high levels of HER2 expression on the tumor surface, persist in spite of the tumor progression as determined by HER2 amplified ctDNA levels measured at progression and HER2 IHC findings on rebiopsies of resistant tumors. These findings offer an unexpected 'precision chemotherapy' rescue potential, in spite of progression under anti HER2 treatment and were confirmed experimentally in a HER2 amplified mCRC PDX (metastatic ColoRectal Carcinoma Patient Derived Xenografts), model generated from the viable biopsy of a relapsing HERACLES patient. In this model a randomized trial comparing TDM1 to pertuzumab versus control (6 animal per arm), showed that T-DM1, but not pertuzumab treated animals achieved tumor disappearance. The results of this experiment confirm the principle strength of targeted toxins which is based on their bipartite structure, with one component binding to a disease-specific cell-surface target molecule and the other conferring cytotoxicity, once internalized. In this case HER2 amplification confer to the tumor the characteristics of a 'molecular sponge' for TDM1 with the trastuzumab moiety targeting the still over-abundant HER2 bound to the cell-surface of anti HER2 resistant tumor cell clusters, thus allowing for a 'surgical' delivery of the emtansine cytotoxicity moiety. Given the good predictability of mCRC PDXs model, as testified by HERACLES TRIAL results (NCT03225937), investigators believe that this activity signal should be tested in the clinic. It is therefore proposed a proof-of-concept trial of T-DM1 in HER2 amplified mCRC patients progressing or relapsing after trastuzumab-lapatinib treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HERACLES RESCUE | Experimental | Drug: Trastuzumab emtansinePatients will receive trastuzumab-emtansine, iv 3,6 mg/kg every 21 days. Patients will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever come first |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histological/confirmed adenocarcinoma of the colon or rectum with metastatic disease not amenable to salvage surgery.
- Progression (PD) during or after therapy with anti-HER2 therapy including those in HERACLES trial cohort A (trastuzumab and lapatinib) within the HERACLES - A trial.
- ECOG PS < 2
- Measurable disease as defined by RECIST 1.1 criteria
- Adequate hematological function as defined by: ANC >= 1.5 x 10^9/L, platelet count >=100 x 10^9/L, hemoglobin >= 10 g/dL.
Key exclusion criteria (12 listed)
- Symptomatic brain metastases
- Active infection
- Interval from last anti HER2 therapy < 2 weeks. Patients in treatment with T-DM1 (provided by third-parties) may be eligible for immediate treatment if not in progression at the time of protocol entry.
- Prior chemotherapy <4 weeks.
- Impaired cardiac function including any of the following: uncontrolled hypertension (systolic >150 mmHg and/or diastolic > 100 mmHg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; chronic heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication, baseline Left Ventricular Ejection Fraction (LVEF) ≤ 55% measured by echocardiography (ECHO)
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 |
|---|---|---|
| Trastuzumab emtansine | Drug | HERACLES RESCUE |
Primary outcome
Objective Response Rate according to RECIST 1.1 criteria
Time frame: every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months
2 secondary outcomes
Description of the frequency and severity of Adverse Events based on the NCI -CTCAE V4.0
Time frame: every 21 days from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months
Progression Free Survival
Time frame: every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- Individual participant dataSharing planned: No
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CRC
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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab emtansine in people with Metastatic Colorectal Cancer, run by Fondazione del Piemonte per l'Oncologia at 3 sites in Italy.
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 12 inclusion and 12 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 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy. 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 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate according to RECIST 1.1 criteria (time frame: every 9 weeks from date of enrollment until the date of first documented progression or date of death for any cause, whichever came first, assessed up to 48 months). 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 31 Oct 2018.