PLATFORM Study of Precision Medicine for Rare Tumors

NCT04423185 | Recruiting Phase 2

• 1 other identifier: NCC2380
• Study Type: interventional
• Target: 770
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rare Tumor

Keywords

Rare tumor; NGS; actionable alterations; precision medicine; immunotherapy

Outcome Measures

Primary Outcomes (1)

• 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 from first dose until confirmed response or progression, assessed up to 2 years.

Secondary Outcomes (9)

• Progression-Free Survival (PFS)

  Measured from first dose until progression, assessed up to 2 years.

• iRECIST Evaluated Progression Free Survival (iPFS)

  Measured from response until progression, assessed up to 2 years.

• Duration of Response (DoR)

  Measured from response until progression, assessed up to 2 years.

• Disease Control Rate (DCR)

  Measured from first dose until confirmed response or progression, whichever came first, assessed up to 2 years.

• Durable Clinical Benefit (DCB)

  Measured from first dose until confirmed response or progression, whichever came first, assessed up to 2 years.

Study Arms (17)

Almonertinib-EGFR mutation

EXPERIMENTAL

Administration: 110 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Almonertinib 110 MG

Dacomitinib-EGFR mutation

EXPERIMENTAL

Administration: 45 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Dacomitinib 45 MG

Alectinib-ALK fusion

EXPERIMENTAL

Administration: 600 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Alectinib 150 MG

Crizotinib-ALK fusion

EXPERIMENTAL

Administration: 250 mg oral bid, to disease progression or intolerable adverse effects.

Drug: Crizotinib 250 MG

Vemurafenib-BRAF mutation

EXPERIMENTAL

Administration: 960 mg oral bid, to disease progression or intolerable adverse effects.

Drug: Vemurafenib 240 MG

Niraparib-BRCA mutation or HRD

EXPERIMENTAL

Administration: 200/300 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Niraparib 200/300 MG

Pyrotinib-HER-2 overexpression/amplification

EXPERIMENTAL

Administration: 400 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Pyrotinib 160/80 MG

Imatinib-CKIT mutation

EXPERIMENTAL

Administration: 400 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Imatinib 400 MG

Palbociclib-CDKN2A mutation

EXPERIMENTAL

Administration: 125 mg oral qd for 21 days q28d, to disease progression or intolerable adverse effects.

Drug: Palbociclib 125mg

Crizotinib-ROS-1 fusion

EXPERIMENTAL

Administration: 250 mg oral bid, to disease progression or intolerable adverse effects.

Drug: Crizotinib 250 MG

Crizotinib-C-MET amplification

EXPERIMENTAL

Administration: 250 mg oral bid, to disease progression or intolerable adverse effects.

Drug: Crizotinib 250 MG

Crizotinib-C-MET mutation

EXPERIMENTAL

Administration: 250 mg oral bid, to disease progression or intolerable adverse effects.

Drug: Crizotinib 250 MG

Pyrotinib-HER-2 mutation

EXPERIMENTAL

Administration: 400 mg oral qd, to disease progression or intolerable adverse effects.

Drug: Pyrotinib 160/80 MG

Sintilimab-PD-1

EXPERIMENTAL

Administration: 200mg q21d, to disease progression or intolerable adverse effects.

Drug: Sintilimab 100MG

Combination ARM-Niraparib & Sintilimab

EXPERIMENTAL

Niraparib (200mg oral qd) combined with Sintilimab (200mg iv q21d) after acquired resistance to Niraparib.

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.

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.

Drug: Palbociclib 125mg; Drug: Atezolizumab 1680 MG

Interventions

Almonertinib 110 MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Almonertinib.

Also known as: HS-10296, AMEILE

Almonertinib-EGFR mutation

Dacomitinib 45 MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying EGFR mutations will be administrated with Dacomitinib.

Also known as: Vizimpro

Dacomitinib-EGFR mutation

Alectinib 150 MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying ALK fusion will be administrated with Alectinib.

Also known as: Alecensa

Alectinib-ALK fusion

Crizotinib 250 MG DRUG

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.

Also known as: Xalkori

Crizotinib-ALK fusion; Crizotinib-C-MET amplification; Crizotinib-C-MET mutation; Crizotinib-ROS-1 fusion

Pyrotinib 160/80 MG DRUG

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.

Also known as: SHR-1258

Pyrotinib-HER-2 mutation; Pyrotinib-HER-2 overexpression/amplification

Imatinib 400 MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying CKIT mutation will be administrated with Imatinib.

Also known as: Gleevec

Imatinib-CKIT mutation

Niraparib 200/300 MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying BRCA1/2 mutation will be administrated with Olaparib.

Also known as: Niraparix

Combination ARM-Niraparib & Sintilimab; Niraparib-BRCA mutation or HRD

Palbociclib 125mg DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying CDKN2A mutation will be administrated with palbociclib.

Also known as: Ibrance

Combination ARM-Palbociclib & Atezolizumab; Palbociclib-CDKN2A mutation

Vemurafenib 240 MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying BRAF mutation will be administrated with Vemurafenib.

Also known as: Zelboraf

Combination ARM-Vemurafenib & Atezolizumab; Vemurafenib-BRAF mutation

Sintilimab 100MG DRUG

Patients with advanced rare tumors who failed to standardized treatment carrying no targeted alterations will be administrated with Sintilimab.

Also known as: Tyvyt

Combination ARM-Niraparib & Sintilimab; Sintilimab-PD-1

Atezolizumab 1680 MG DRUG

Patients with BRAF mutation treated with vemurafenib, after acquired resistance, will combine vemurafenib with atezolizumab.

Also known as: TECENTRIQ

Combination ARM-Palbociclib & Atezolizumab; Combination ARM-Vemurafenib & Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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;

You may not qualify if:

• 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.
• 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.
• 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:

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer hospital Chinese Academy of Medical Sciences

Beijing, 100021, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 34083331 DERIVED

MeSH Terms

Interventions

aumolertinib; dacomitinib; alectinib; Crizotinib; pyrotinib; Imatinib Mesylate; niraparib; palbociclib; Vemurafenib; sintilimab; atezolizumab

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Pyrimidines; Sulfonamides; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ning Li, Doctor

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  STUDY CHAIR

Central Study Contacts

Ning Li, Doctor

CONTACT

+8601087788713; lining@cicams.ac.cn

Shuhang Wang, Doctor

CONTACT

+8613581809307; wangshuhang@cicams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Office of Clinical Trial Center, CancerIHCAMS

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: June 9, 2020
• Study Start: August 15, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)