Rare TumorPhase 2NCT04423185
PLATFORM Study of Precision Medicine for Rare Tumors
A Phase 2 study testing Almonertinib 110 MG, Dacomitinib 45 MG and Alectinib 150 MG in people with Rare Tumor, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rare Tumor
- What is being tested?
- Almonertinib 110 MG, Dacomitinib 45 MG and Alectinib 150 MG
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 770 participants
- Where
- 1 siteChina
- Study dates
- 15 Aug 2020to 1 Jul 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Male or female, the age at the time of signing the informed consent is no less than 18 years old;
- Patients with advanced or metastatic rare solid tumor confirmed by histological confirmed;
- ECOG score is 0 or 1; ECOG score needs to be evaluated 7 days before the first treatment;
- Expected survival ≥12 weeks;
- According to Response Evaluation Criteria in Solid Tumor (RECIST 1.1), there is at least one imaging measurable lesions, which has obvious disease progress before radiotherapy or after radiotherapy;
- Within the scope of CMPA approved drug indications, the disease has progressed after the standard treatment recommended by NCCN or CSCO guidelines (if there is standard treatment, the recommended level is IA-IIA), or there is no standard effective treatment plan, or it is no longer suitable for standard anti-tumor treatment, or the patients refuse the standard treatment plan;
Show all 14Show fewer
- Fresh biopsy tissue samples (obtained within 12 weeks before the first use of the drug, 4 pieces of coarse needle biopsy must be provided, and no other anti-tumor treatment, systemic anti infection treatment, vaccination, et al.) and peripheral blood samples must be provided for molecular typing;
- Must have a primary or metastatic paraffin specimen (without radiotherapy) other than bone metastatic lesions before enrollment (within 2 years, 15-20 sheets, 4-6μm thick white slices, of which 5 need to be glued and baked ). If requirements are not met, investigator are allowed the decision to enroll subjects according to the specific situation.
- If there is pleural or peritoneal effusion, the specimens must be taken for pathological cytological examination of which 300 ml samples must be provided;
- In the condition that the primary lesions biopsy specimen has been provided, if the metastatic lesion is able to be biopsied, it is suggested to keep the specimen for pathological testing and provide fresh tissue specimen (optional); when obtaining EGFR mutation, ALK fusion, ROS-1 fusion, C-MET amplification, C-MET mutation, BRAF mutation, BRCA1/2 mutation, C-KIT mutation, HER-2 mutation HER-2 over expression/amplification, CDKN2A mutation patients will enroll in corresponding sub-study of targeted therapy; if no above mentioned actionable mutation is identified, patients will enroll immunotherapy sub-study. (Each sub-study has separate inclusion and exclusion criteria besides general ones)
- After the progression of the subject's disease, if conditions permit, fresh tissue samples shall be obtained from the same biopsy lesions and the metastasis lesions of the previously obtained samples;
- Toxic and side effects caused by previous treatment need to be restored to ≤ Grade 1 or returned to the baseline value (NCI-CTCAE version 5.0, except for hair loss);
- Negative pregnancy test (only applicable for women with childbearing potential). No childbearing potential is defined as being postmenopausal for longer than one year or having undergone surgical sterilization or hysterectomy. All patients (male and female) agree to use an effective form of contraceptive measures and continue its use for the duration of treatment and within 8 weeks after the end of treatment;
- Signed, written informed consent of volunteers that join the group shall follow the study treatment plan, follow-up plan and cooperate to observe the adverse events and efficacy.
Who cannot join
- History of PD-1 / PD-L1 drug treatment.
- History of the targeted drug treatment of this study.
- Allergies towards drug ingredients or excipients in this study.
- History of interstitial lung disease or radiation pneumonitis of any type.
- Central Nervous System (CNS) metastases with brain metastases-related symptoms, which is not stable in neurology, or need to increase steroid dosage to control CNS disease. (Note: Patients with controlled CNS metastasis are eligible to participate in this study. Before entering the study, subject must have completed radiotherapy or CNS tumor metastasis surgery for more than fourteen days, neurological function must be in a stable state with no new neurological defects found in the clinical examination and no new problems found in the CNS imaging examination. If necessity arises for subjects to use steroids for CNS metastases treatment, said steroid treatment dose must have reached stable treatment for ≥ 3 months at least two weeks before entering the study.
- Current uncontrollable third cavity effusion, such as a large amount of pleural effusion or ascites.
Show all 45Show fewer
- Unmeet the inclusion criteria of sub scheme.
- Major surgical operations or incomplete healing of injury within 28 days prior to study treatment's first administration and chest radiotherapy of > 30 Gy within 6 months.
- History of receiving other investigational drugs within 14 days or 5 half-lives (whichever is longer) prior to the first administration.
- History of receiving live vaccine within 30 days prior to the first administration. Seasonal influenza vaccines that do not contain live viruses are allowed.
- History of hypersensitivity to the active ingredients or non-active excipients of the study drug, hypersensitivity to drugs with chemical structure similar to the study drug or hypersensitivity to similar drugs of the study drug.
- Current active infection requiring systemic treatment (antibiotics); or any of the following:
- HIV positive or known history of acquired immunodeficiency syndrome;
- Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is defined as HBsAg positive and the number of HBV DNA copies exceeds the upper limit of normal value, or HCV AB positive;
- Active tuberculosis (with exposure history or positive tuberculosis test; with clinical and / or imaging manifestations);
- Positive antibody of Treponema Pallidum.
- Current evidenced uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension [i.e., still greater than or equal to CTCAE Grade 3 hypertension after drug treatment]).
- History of myocardial infarction, coronary artery / peripheral artery bypass or cerebrovascular accident within 3 months.
- Diagnosed with a second type of malignant tumor within 5 years before the first diagnosis of a rare solid tumor (excluding completely resected basal cell carcinoma, bladder carcinoma in situ, cervical carcinoma in situ).
- History of receiving of any organ transplantation, including allogeneic stem cell transplantation. Transplantation without immunosuppression (corneal transplantation, hair transplantation) is excluded.
- Cardiovascular disease or symptom includes any of the following:
- History of Congestive Heart Failure requiring treatment and of New York Heart Association class III / IV CHF (see Appendix 3) ;
- Current ventricular arrhythmia requiring antiarrhythmic drugs treatment, or uncontrollable or unstable arrhythmia;
- Severe conduction disorder (such as grade II or III AV block);
- Angina requiring treatment;
- QT interval (QTC) of 12 lead ECG is ≥ 450 ms in male and ≥ 470 MS in female;
- History of congenital long QT syndrome, congenital short QT syndrome, torsade de pointe or pre-excitation syndrome;
- History of LVEF decline to below 50% determined by echocardiography or MUGA scan;
- History of myocardial infarction in the past 6 months.
- Inadequate bone marrow reserve or organ function evidenced by the following laboratory results:
- Absolute value of neutrophils < 1.5 × 109 / L;
- Platelet count < 100 × 109 / L (transfusion dependent patients should be excluded from this study);
- Hemoglobin < 90g / L;
- ALT is > 2.5 x Upper Limit of Normal (ULN) If there is no clear liver metastases, ALT > 5 x ULN if there is liver metastases;
- Aspartate aminotransferase (AST) > 2.5 x ULN If there is no definite liver metastases. AST > 5x ULN if there is liver metastases;
- Total bilirubin > 1.5 x ULN if there is no liver metastases; Total bilirubin > 3 x ULN if there is definite Gilbert syndrome (Unconjugated Hyperbilirubinemia) or liver metastases;
- Creatinine > 1.5 x ULN with Creatinine clearance < 50 ml / min (measured value, or calculated value by Cockcroft Gault formula); Only when Creatinine > 1.5 x ULN, Creatinine clearance needs to be checked for confirmation;
- If bone metastasis is present and investigator concluded that liver function is adequate, the increase of ALP alone will not be excluded;
- Coagulation function: INR, PT, APTT> 1.5 times ULN (whether the patients using or not using anticoagulant drugs can be enrolled is determined by the investigator).
- Myocardial enzyme CK and CKMB test values are not in the normal range;
- The examination value of thyroid function is not within the normal range or it is not slightly abnormal but does not need treatment.
- History of swallowing dysfunction, active gastrointestinal disease or other diseases that significantly affect the absorption, distribution, metabolism and excretion of oral drugs. The patients with history of subtotal gastrectomy. (Note: this standard is not applicable to the sub schemes with the investigational drug as injection).
- Pregnant or lactating women.
- Serious medical or mental illness that may affect program compliance and tolerance to treatment.
- Those investigators believe that patients with other potential risks are not suitable for this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Cancer hospital Chinese Academy of Medical Sciences
Beijing, 100021
About this study
Official title: Platform Study of Genotyping Guided Precision Medicine for Rare Tumors in China
A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment.
Read the detailed description
Based on the fact that a high incidence rate (14.2%) of rare tumor (incidence rate <2.5/100,000) as defined in this study according to the National Cancer Registry data from National Cancer Center of China, as well as the current status of lacking guidelines and consensus of rare tumor treatment. We proposed this study "A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment", aims to evaluate the safety and efficacy of targeted drugs of specific tumor-driven genes in patients with advanced rare solid tumors with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (PD-1) inhibitors in patients with advanced rare solid tumors without actionable alterations. Patients with advanced rare tumors who failed to standardized treatment carrying actionable alterations as "EGFR mutation (exon 19 deletion mutation, L858R replacement mutation), ALK gene fusion, ROS-1 gene fusion, C-MET gene amplification or mutation (D1010 mutation, 14 exon mutation, y1003 mutation), BRAF mutation, CDKN2A mutation, BRCA1/2 mutation, HER-2 mutation, HER-2 over expression/amplification, C-KIT mutation", will enroll targeted therapy arms and be given corresponding targeted drugs (Dacomitinib, Crizotinib). And patients without targeted alterations mentioned above will enroll PD-1 inhibitor arm and to be treated with Sintilimab. After acquired resistance patients treated with olaparib and palbociclib will receive combination treatment with durvalumab. After acquired resistance patients treated with vemurafenib will receive combination treatment with atezolizumab. The statistics of current study adopts Simon's two-stage Minimax design: In the first stage of clinical research, 12 subjects will be observed. If the number of CR + PR is less than 1, the trial will be terminated, otherwise, the group will continue to expand to 16 subjects. Therefore, in the first stage, there are 12*5/(1-10%)=54 patients of targeted treatment group and 126 patients in the immunotherapy group, 180 patients totally in the first stage. If they all enter the second stage, the final target treatment group is 16*5/(1-10%) = 72 patients and the immunotherapy group which has 168 patients which brings to a total of 240 patients. The sample size of the study shall be adjusted according to the interim analysis. Primary Endpoint of this study is objective response rate (ORR) in immunotherapy group and targeted therapy group assessed by Blinded Independent Central Review (BICR) and investigator. Secondary Endpoints are Progression-Free Survival (PFS) in the targeted treatment group assessed by Blinded Independent Central Review and investigator; PFS (RECIST 1.1) and iPFS (iRECIST) in the single drug immunotherapy group assessed by Blinded Independent Central Review and investigator; Duration of Response (DoR) in the targeted therapy and single immunotherapy groups assessed by the investigator; Durable Clinical Benefit (DCB) in the single drug immunotherapy group; Incidence of Adverse Events (AE) in subjects ect.
- Conditions
- Rare Tumor
- Being tested
- Almonertinib 110 MG, Dacomitinib 45 MG, Alectinib 150 MG, Crizotinib 250 MG, Pyrotinib 160/80 MG
- Keywords
- Rare tumor, NGS, actionable alterations, precision medicine, immunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Almonertinib 110 MGDrug
Also called HS-10296, AMEILE
Patients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Almonertinib.
Dacomitinib 45 MGDrug
Also called Vizimpro
Patients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Dacomitinib.
Alectinib 150 MGDrug
Also called Alecensa
Patients with advanced rare tumors who failed to standardized treatment carrying ALK fusion will be administrated with Alectinib.
Crizotinib 250 MGDrug
Also called Xalkori
Patients with advanced rare tumors who failed to standardized treatment carrying ALK fusion, ROS-1 fusion, C-MET amplification, C-MET mutation will be administrated with Crizotinib.
Pyrotinib 160/80 MGDrug
Also called SHR-1258
Patients with advanced rare tumors who failed to standardized treatment carrying HER-2 mutation or HER-2 over expression/amplification will be administrated with Pyrotinib.
Imatinib 400 MGDrug
Also called Gleevec
Patients with advanced rare tumors who failed to standardized treatment carrying CKIT mutation will be administrated with Imatinib.
Niraparib 200/300 MGDrug
Also called Niraparix
Patients with advanced rare tumors who failed to standardized treatment carrying BRCA1/2 mutation will be administrated with Olaparib.
Palbociclib 125mgDrug
Also called Ibrance
Patients with advanced rare tumors who failed to standardized treatment carrying CDKN2A mutation will be administrated with palbociclib.
Vemurafenib 240 MGDrug
Also called Zelboraf
Patients with advanced rare tumors who failed to standardized treatment carrying BRAF mutation will be administrated with Vemurafenib.
Sintilimab 100MGDrug
Also called Tyvyt
Patients with advanced rare tumors who failed to standardized treatment carrying no targeted alterations will be administrated with Sintilimab.
Atezolizumab 1680 MGDrug
Also called TECENTRIQ
Patients with BRAF mutation treated with vemurafenib, after acquired resistance, will combine vemurafenib with atezolizumab.
| Study group | Role | What they receive |
|---|---|---|
| Almonertinib-EGFR mutation | Experimental | Administration: 110 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Almonertinib 110 MG |
| Dacomitinib-EGFR mutation | Experimental | Administration: 45 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Dacomitinib 45 MG |
| Alectinib-ALK fusion | Experimental | Administration: 600 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Alectinib 150 MG |
| Crizotinib-ALK fusion | Experimental | Administration: 250 mg oral bid, to disease progression or intolerable adverse effects. Receives: Drug: Crizotinib 250 MG |
| Vemurafenib-BRAF mutation | Experimental | Administration: 960 mg oral bid, to disease progression or intolerable adverse effects. Receives: Drug: Vemurafenib 240 MG |
| Niraparib-BRCA mutation or HRD | Experimental | Administration: 200/300 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Niraparib 200/300 MG |
| Pyrotinib-HER-2 overexpression/amplification | Experimental | Administration: 400 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Pyrotinib 160/80 MG |
| Imatinib-CKIT mutation | Experimental | Administration: 400 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Imatinib 400 MG |
| Palbociclib-CDKN2A mutation | Experimental | Administration: 125 mg oral qd for 21 days q28d, to disease progression or intolerable adverse effects. Receives: Drug: Palbociclib 125mg |
| Crizotinib-ROS-1 fusion | Experimental | Administration: 250 mg oral bid, to disease progression or intolerable adverse effects. Receives: Drug: Crizotinib 250 MG |
| Crizotinib-C-MET amplification | Experimental | Administration: 250 mg oral bid, to disease progression or intolerable adverse effects. Receives: Drug: Crizotinib 250 MG |
| Crizotinib-C-MET mutation | Experimental | Administration: 250 mg oral bid, to disease progression or intolerable adverse effects. Receives: Drug: Crizotinib 250 MG |
| Pyrotinib-HER-2 mutation | Experimental | Administration: 400 mg oral qd, to disease progression or intolerable adverse effects. Receives: Drug: Pyrotinib 160/80 MG |
| Sintilimab-PD-1 | Experimental | Administration: 200mg q21d, to disease progression or intolerable adverse effects. Receives: Drug: Sintilimab 100MG |
| Combination ARM-Niraparib & Sintilimab | Experimental | Niraparib (200mg oral qd) combined with Sintilimab (200mg iv q21d) after acquired resistance to Niraparib. Receives: Drug: Niraparib 200/300 MG; Drug: Sintilimab 100MG |
| Combination ARM-Vemurafenib & Atezolizumab | Experimental | Vemurafenib (960 mg oral bid) \& Atezolizumab (1200mg iv q21d) after acquired resistance to Vemurafenib. Receives: Drug: Vemurafenib 240 MG; Drug: Atezolizumab 1680 MG |
| Combination ARM-Palbociclib & Atezolizumab | Experimental | Palbociclib (125 mg oral qd for 21 days q28d) combined with Atezolizumab (1680mg iv q28d) after acquired resistance to Palbociclib. Receives: Drug: Palbociclib 125mg; Drug: Atezolizumab 1680 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The percentage of patients with a confirmed Blinded Independent Central Review (BICR) and investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1.
Measured: Measured from first dose until confirmed response or progression, assessed up to 2 years.
Secondary outcomes (9)
Progression-Free Survival (PFS)
The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression).
Measured: Measured from first dose until progression, assessed up to 2 years.
iRECIST Evaluated Progression Free Survival (iPFS)
The interval between the initiation of study treatment and the first documentation of CUPD (second confirmation of Disease Progression) or death due to any cause as defined by the iRECIST standard in the single drug immunotherapy group
Measured: Measured from response until progression, assessed up to 2 years.
Duration of Response (DoR)
The time from the date of first response until date of disease progression or death in the absence of disease progression.
Measured: Measured from response until progression, assessed up to 2 years.
Disease Control Rate (DCR)
The percentage of patients treated with targeted and single immunotherapy assessed by the investigator,
Measured: Measured from first dose until confirmed response or progression, whichever came first, assessed up to 2 years.
Durable Clinical Benefit (DCB)
Partial Response (PR) or Complete Response (CR) or Stable Disease (SD) in the single drug immunotherapy group and without Disease Progression at more than six months.
Measured: Measured from first dose until confirmed response or progression, whichever came first, assessed up to 2 years.
Overall survival (OS)
The median survival time of patients
Measured: Measured from first dose until death or final cohort data cut-off, whichever came first, assessed up to 2 years.
One year of Overall Survival rate (1-year OS rate)
Percentage of patients who is alive at 1-year from first dose of treatment.
Measured: Measured from first dose until death, assessed up to 2 years.
Incidence of Adverse Events (AE) in subjects
To evaluate safety and tolerability of each study treatment.
Measured: Continuously from first dose to end of safety follow up after study treatment discontinuation, assessed up to 2 years.
The 6-month PFS rate
The proportion of patients who are alive and progression-free more than 6 months after the first dose of study therapy Progression-free Survival (PFS) the proportion of patients with PFS ≥ 6 months in the total enrollment since the start of the study.
Measured: Measured from response until progression, assessed up to 2 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start15 Aug 2020
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rare TumorStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 770 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ning Li, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Investigators
- Ning Li, Doctor, Study chair, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04423185
- Sponsor's protocol ID
- NCC2380
- Status last verified
- Feb 2025
- First submitted
- 27 May 2020
- Last updated
- 11 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang S, Huang HY, Wu D, Fang H, Ying J, Bai Y, Yu Y, Fang Y, Jiang N, Sun C, Yu A, Fan Q, Xing S, Ni Y, Zhang W, Wu C, Ji X, Wang H, Guo Y, Tang Q, Wang Y, Tang Y, Li N. Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours. BMJ Open. 2021 Jun 3;11(6):e044543. doi: 10.1136/bmjopen-2020-044543.
PubMed 34083331
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platform Study of Genotyping Guided Precision Medicine for Rare Tumors in China
- ClinicalTrials.gov ID
- NCT04423185
- Acronym / sponsor ID
- NCC2380
- Conditions
- Rare Tumor
- Keywords
- Rare tumor, NGS, actionable alterations, precision medicine, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 770 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 15 Aug 2020 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 9 Jun 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.
A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment.
Detailed description
Based on the fact that a high incidence rate (14.2%) of rare tumor (incidence rate <2.5/100,000) as defined in this study according to the National Cancer Registry data from National Cancer Center of China, as well as the current status of lacking guidelines and consensus of rare tumor treatment. We proposed this study "A Phase II, open label, non-randomized, multiple-arm, single-center clinical trial in patients with advanced rare solid tumors who failed to standard treatment", aims to evaluate the safety and efficacy of targeted drugs of specific tumor-driven genes in patients with advanced rare solid tumors with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (PD-1) inhibitors in patients with advanced rare solid tumors without actionable alterations. Patients with advanced rare tumors who failed to standardized treatment carrying actionable alterations as "EGFR mutation (exon 19 deletion mutation, L858R replacement mutation), ALK gene fusion, ROS-1 gene fusion, C-MET gene amplification or mutation (D1010 mutation, 14 exon mutation, y1003 mutation), BRAF mutation, CDKN2A mutation, BRCA1/2 mutation, HER-2 mutation, HER-2 over expression/amplification, C-KIT mutation", will enroll targeted therapy arms and be given corresponding targeted drugs (Dacomitinib, Crizotinib). And patients without targeted alterations mentioned above will enroll PD-1 inhibitor arm and to be treated with Sintilimab. After acquired resistance patients treated with olaparib and palbociclib will receive combination treatment with durvalumab. After acquired resistance patients treated with vemurafenib will receive combination treatment with atezolizumab. The statistics of current study adopts Simon's two-stage Minimax design: In the first stage of clinical research, 12 subjects will be observed. If the number of CR + PR is less than 1, the trial will be terminated, otherwise, the group will continue to expand to 16 subjects. Therefore, in the first stage, there are 12*5/(1-10%)=54 patients of targeted treatment group and 126 patients in the immunotherapy group, 180 patients totally in the first stage. If they all enter the second stage, the final target treatment group is 16*5/(1-10%) = 72 patients and the immunotherapy group which has 168 patients which brings to a total of 240 patients. The sample size of the study shall be adjusted according to the interim analysis. Primary Endpoint of this study is objective response rate (ORR) in immunotherapy group and targeted therapy group assessed by Blinded Independent Central Review (BICR) and investigator. Secondary Endpoints are Progression-Free Survival (PFS) in the targeted treatment group assessed by Blinded Independent Central Review and investigator; PFS (RECIST 1.1) and iPFS (iRECIST) in the single drug immunotherapy group assessed by Blinded Independent Central Review and investigator; Duration of Response (DoR) in the targeted therapy and single immunotherapy groups assessed by the investigator; Durable Clinical Benefit (DCB) in the single drug immunotherapy group; Incidence of Adverse Events (AE) in subjects ect.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 17
| Arm | Type | Receives |
|---|---|---|
| Almonertinib-EGFR mutation | Experimental | Drug: Almonertinib 110 MGAdministration: 110 mg oral qd, to disease progression or intolerable adverse effects. |
| Dacomitinib-EGFR mutation | Experimental | Drug: Dacomitinib 45 MGAdministration: 45 mg oral qd, to disease progression or intolerable adverse effects. |
| Alectinib-ALK fusion | Experimental | Drug: Alectinib 150 MGAdministration: 600 mg oral qd, to disease progression or intolerable adverse effects. |
| Crizotinib-ALK fusion | Experimental | Drug: Crizotinib 250 MGAdministration: 250 mg oral bid, to disease progression or intolerable adverse effects. |
| Vemurafenib-BRAF mutation | Experimental | Drug: Vemurafenib 240 MGAdministration: 960 mg oral bid, to disease progression or intolerable adverse effects. |
| Niraparib-BRCA mutation or HRD | Experimental | Drug: Niraparib 200/300 MGAdministration: 200/300 mg oral qd, to disease progression or intolerable adverse effects. |
| Pyrotinib-HER-2 overexpression/amplification | Experimental | Drug: Pyrotinib 160/80 MGAdministration: 400 mg oral qd, to disease progression or intolerable adverse effects. |
| Imatinib-CKIT mutation | Experimental | Drug: Imatinib 400 MGAdministration: 400 mg oral qd, to disease progression or intolerable adverse effects. |
| Palbociclib-CDKN2A mutation | Experimental | Drug: Palbociclib 125mgAdministration: 125 mg oral qd for 21 days q28d, to disease progression or intolerable adverse effects. |
| Crizotinib-ROS-1 fusion | Experimental | Drug: Crizotinib 250 MGAdministration: 250 mg oral bid, to disease progression or intolerable adverse effects. |
| Crizotinib-C-MET amplification | Experimental | Drug: Crizotinib 250 MGAdministration: 250 mg oral bid, to disease progression or intolerable adverse effects. |
| Crizotinib-C-MET mutation | Experimental | Drug: Crizotinib 250 MGAdministration: 250 mg oral bid, to disease progression or intolerable adverse effects. |
| Pyrotinib-HER-2 mutation | Experimental | Drug: Pyrotinib 160/80 MGAdministration: 400 mg oral qd, to disease progression or intolerable adverse effects. |
| Sintilimab-PD-1 | Experimental | Drug: Sintilimab 100MGAdministration: 200mg q21d, to disease progression or intolerable adverse effects. |
| Combination ARM-Niraparib & Sintilimab | Experimental | Drug: Niraparib 200/300 MG, Drug: Sintilimab 100MGNiraparib (200mg oral qd) combined with Sintilimab (200mg iv q21d) after acquired resistance to Niraparib. |
| Combination ARM-Vemurafenib & Atezolizumab | Experimental | Drug: Vemurafenib 240 MG, Drug: Atezolizumab 1680 MGVemurafenib (960 mg oral bid) \& Atezolizumab (1200mg iv q21d) after acquired resistance to Vemurafenib. |
| Combination ARM-Palbociclib & Atezolizumab | Experimental | Drug: Palbociclib 125mg, Drug: Atezolizumab 1680 MGPalbociclib (125 mg oral qd for 21 days q28d) combined with Atezolizumab (1680mg iv q28d) after acquired resistance to Palbociclib. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Male or female, the age at the time of signing the informed consent is no less than 18 years old;
- Patients with advanced or metastatic rare solid tumor confirmed by histological confirmed;
- ECOG score is 0 or 1; ECOG score needs to be evaluated 7 days before the first treatment;
- Expected survival ≥12 weeks;
- According to Response Evaluation Criteria in Solid Tumor (RECIST 1.1), there is at least one imaging measurable lesions, which has obvious disease progress before radiotherapy or after radiotherapy;
Key exclusion criteria (45 listed)
- History of PD-1 / PD-L1 drug treatment.
- History of the targeted drug treatment of this study.
- Allergies towards drug ingredients or excipients in this study.
- History of interstitial lung disease or radiation pneumonitis of any type.
- Central Nervous System (CNS) metastases with brain metastases-related symptoms, which is not stable in neurology, or need to increase steroid dosage to control CNS disease. (Note: Patients with controlled CNS metastasis are eligible to participate in this study. Before entering the study, subject must have completed radiotherapy or CNS tumor metastasis surgery for more than fourteen days, neurological function must be in a stable state with no new neurological defects found in the clinical examination and no new problems found in the CNS imaging examination. If necessity arises for subjects to use steroids for CNS metastases treatment, said steroid treatment dose must have reached stable treatment for ≥ 3 months at least two weeks before entering the study.
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 |
|---|---|---|
| Almonertinib 110 MGAlso: HS-10296, AMEILEPatients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Almonertinib. | Drug | Almonertinib-EGFR mutation |
| Dacomitinib 45 MGAlso: VizimproPatients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Dacomitinib. | Drug | Dacomitinib-EGFR mutation |
| Alectinib 150 MGAlso: AlecensaPatients with advanced rare tumors who failed to standardized treatment carrying ALK fusion will be administrated with Alectinib. | Drug | Alectinib-ALK fusion |
| Crizotinib 250 MGAlso: XalkoriPatients with advanced rare tumors who failed to standardized treatment carrying ALK fusion, ROS-1 fusion, C-MET amplification, C-MET mutation will be administrated with Crizotinib. | Drug | Crizotinib-ALK fusion, Crizotinib-C-MET amplification, Crizotinib-C-MET mutation, Crizotinib-ROS-1 fusion |
| Pyrotinib 160/80 MGAlso: SHR-1258Patients with advanced rare tumors who failed to standardized treatment carrying HER-2 mutation or HER-2 over expression/amplification will be administrated with Pyrotinib. | Drug | Pyrotinib-HER-2 mutation, Pyrotinib-HER-2 overexpression/amplification |
| Imatinib 400 MGAlso: GleevecPatients with advanced rare tumors who failed to standardized treatment carrying CKIT mutation will be administrated with Imatinib. | Drug | Imatinib-CKIT mutation |
| Niraparib 200/300 MGAlso: NiraparixPatients with advanced rare tumors who failed to standardized treatment carrying BRCA1/2 mutation will be administrated with Olaparib. | Drug | Combination ARM-Niraparib & Sintilimab, Niraparib-BRCA mutation or HRD |
| Palbociclib 125mgAlso: IbrancePatients with advanced rare tumors who failed to standardized treatment carrying CDKN2A mutation will be administrated with palbociclib. | Drug | Combination ARM-Palbociclib & Atezolizumab, Palbociclib-CDKN2A mutation |
| Vemurafenib 240 MGAlso: ZelborafPatients with advanced rare tumors who failed to standardized treatment carrying BRAF mutation will be administrated with Vemurafenib. | Drug | Combination ARM-Vemurafenib & Atezolizumab, Vemurafenib-BRAF mutation |
| Sintilimab 100MGAlso: TyvytPatients with advanced rare tumors who failed to standardized treatment carrying no targeted alterations will be administrated with Sintilimab. | Drug | Combination ARM-Niraparib & Sintilimab, Sintilimab-PD-1 |
| Atezolizumab 1680 MGAlso: TECENTRIQPatients with BRAF mutation treated with vemurafenib, after acquired resistance, will combine vemurafenib with atezolizumab. | Drug | Combination ARM-Palbociclib & Atezolizumab, Combination ARM-Vemurafenib & Atezolizumab |
Primary outcome
Objective Response Rate (ORR)
Time frame: Measured from first dose until confirmed response or progression, assessed up to 2 years.
The percentage of patients with a confirmed Blinded Independent Central Review (BICR) and investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1.
9 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Measured from first dose until progression, assessed up to 2 years.
iRECIST Evaluated Progression Free Survival (iPFS)
Time frame: Measured from response until progression, assessed up to 2 years.
Duration of Response (DoR)
Time frame: Measured from response until progression, assessed up to 2 years.
Disease Control Rate (DCR)
Time frame: Measured from first dose until confirmed response or progression, whichever came first, assessed up to 2 years.
Durable Clinical Benefit (DCB)
Time frame: Measured from first dose until confirmed response or progression, whichever came first, assessed up to 2 years.
Overall survival (OS)
Time frame: Measured from first dose until death or final cohort data cut-off, whichever came first, assessed up to 2 years.
One year of Overall Survival rate (1-year OS rate)
Time frame: Measured from first dose until death, assessed up to 2 years.
Incidence of Adverse Events (AE) in subjects
Time frame: Continuously from first dose to end of safety follow up after study treatment discontinuation, assessed up to 2 years.
The 6-month PFS rate
Time frame: Measured from response until progression, assessed up to 2 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Derived from this study: PubMed 34083331Wang S, Huang HY, Wu D, Fang H, Ying J, Bai Y, Yu Y, Fang Y, Jiang N, Sun C, Yu A, Fan Q, Xing S, Ni Y, Zhang W, Wu C, Ji X, Wang H, Guo Y, Tang Q, Wang Y, Tang Y, Li N. Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours. BMJ Open. 2021 Jun 3;11(6):e044543. doi: 10.1136/bmjopen-2020-044543.
- Individual participant dataSharing planned: No
Related trials for Rare Tumor
RecruitingObservational study
NCI Childhood Cancer Data Initiative (CCDI) Led Pediatric, Adolescent, and Young Adult Rare Cancer Registry for Very Rare Solid Tumors
Very Rare Tumors, Very Rare Cancers
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Children and Adults With Chordoma
Chordoma
Active, not recruitingPhase 2
Testing the Combination of Anti-cancer Drugs Atezolizumab and Tiragolumab in People With Advanced Stage Rare Cancers, RARE3 Trial
Advanced Rare Malignant Solid Neoplasm, Rare Malignant Solid Neoplasm
RecruitingPhase 1/2
A Study of BH-30643 in Subjects With Locally Advanced or Metastatic NSCLC Harboring EGFR and/or HER2 Mutations
NSCLC (Advanced Non-small Cell Lung Cancer)
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.
Ning Li, Doctor study chair
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Almonertinib 110 MG, Dacomitinib 45 MG and Alectinib 150 MG in people with Rare Tumor, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
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 45 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: looking for participants now, as of the sponsor's last update on 11 Feb 2025. 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 China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ning Li, Doctor (+8601087788713, lining@cicams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Measured from first dose until confirmed response or progression, assessed up to 2 years.). 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 NCT04423185, 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 11 Feb 2025.