A Clinical Study to evaluate the Safety, Tolerability, and the effects of VX-970/M6620 in combination with Chemotherapy on the body in Participantswith Advanced Solid Tumors
- Conditions
- cancer (malignant solid tumors)MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003126-25-GB
- Lead Sponsor
- Merck KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 195
Subjects who meet all of the following inclusion criteria will be eligible for this study:
1.Male and female subjects =18 years of age
2.Disease status
Parts A and B/B2: Histologically or cytologically confirmed advanced solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective, or for whom regimens containing gemcitabine, cisplatin, and/or etoposide might be considered, and with measurable disease according to RECIST criteria (Version 1.1)
Part C1:
Pre-screening: subjects who are not current candidates for study drug treatment or do not elect to be candidates at this time, but may be candidates in the future:
a.Advanced (metastatic or locally-advanced unresectable and not eligible for definitive treatment, e.g., surgery/radiotherapy) histologically confirmed NSCLC
b.Available historical tumor specimen available for shipment to the sponsor as confirmed by the investigator unless otherwise agreed to by the sponsor or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the patient
c.Received or did not tolerate standard approved targeted therapy, if appropriate for tumor genotype (e.g., targeted therapies for ALK rearrangement or EGFR activating mutations)
Screening: subjects who are current candidates for study drug treatment:
a.Measurable disease according to RECIST criteria (Version 1.1)
b.Meet inclusion criteria a through c for Part C1 pre-screening.
Part C2:
a.Advanced (locally-advanced incurable or metastatic), histologically confirmed estrogen receptor, progesterone receptor, and HER2 negative breast cancer
b.Adequate available historical tumor specimen (core biopsy or surgical specimen; fine needle aspirate inadequate) available for shipment to the sponsor as confirmed by the investigator unless otherwise agreed to by the sponsor, or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the patient
c.Measurable disease according to RECIST criteria (Version 1.1)
Part C3:
a.Advanced (locally-advanced incurable or metastatic), histologically confirmed SCLC that is platinum-resistant, defined as disease progression during initial treatment with a platinum-based regimen or progression within 90 days of completion of platinum therapy. Subjects with platinum-resistant disease may receive a second-line non-platinum-based chemotherapy and subsequently be enrolled to this study. Subjects who received and are resistant to a second-line platinum-based chemotherapy, (i.e., progressing on or within 90 days of treatment with a platinum-based regimen) may also be enrolled into the study.
b. Adequate available historical tumor specimen if available (core biopsy or surgical specimen; fine needle aspirate inadequate) or willing to provide a tumor biopsy (core) if the biopsy may be considered as part of standard clinical practice for the patient. If a historical sample is unavailable, a subject may be enrolled at the discretion of the investigator and sponsor.
c. Measurable disease according to RECIST criteria (Version 1.1)
3.WHO performance status of 0 or 1
4.Life expectancy of =12 weeks
5.Hematological and biochemical indices within the ranges shown below at screening. No clinically significant change in these values must be confirmed on the first day of dosing, before study drug administration.
a.Hemoglobin: =8.0 g/dL
b.Absolute neutrophi
1.Radiotherapy (except for palliative reasons) endocrine therapy, immunotherapy, or chemotherapy during the previous 4 weeks (6 weeks for nitrosoureas and Mitomycin C, and 4 weeks for investigational medicinal products) or less than 4 drug half-lives.
2.Prior chemotherapy
Parts A and B/B2:
•Greater than 6 cycles of prior treatment with cisplatin and/or carboplatin, unless discussed with and approved by Vertex medical monitor.
•Subjects with a known history of Grade 4 thrombocytopenia or Grade 4 neutropenia while receiving prior therapy, unless discussed with and approved by Vertex medical monitor.
Part C1:
a.Any cytotoxic chemotherapy beyond 1 line of platinum-based chemotherapy. One additional line of non-platinum based therapy in the advanced setting is allowed.
b.Any prior gemcitabine for the treatment of NSCLC in any setting within 6 months
Part C2:
a.Any prior platinum therapy in the adjuvant or neoadjuvant within 6 months of screening
b.Relapse within 3 months of completion of prior adjuvant or neoadjuvant chemotherapy
c.Any prior chemotherapy in the metastatic setting except a taxane and/or an anthracycline and 1 other non-platinium-based chemotherapy in the first- and second-line metastatic setting
Part C3:
a. Prior platinum-sensitive subjects, unless they progress on or within 90 days of completion of platinum-based regimen
b. There is no restriction on prior immunotherapy or targeted therapy in the metastatic setting unless combined together with a cytotoxic agent
c. During prior carboplatin therapy, requirement for dose reduction below AUC 5 mg.min/mL or discontinuation of carboplatin for toxicity or lack of tolerability. However, the subject would be eligible to receive cisplatin as long as otherwise meets criteria and is discussed with sponsor
3.Biomarkers
Part C1:
a. Subjects who are known to be TP53 wild-type, unless they are determined to have ATM loss of expression during screening or pre-screening or until all the planned subjects with TP53 mutation are enrolled as determined by the medical monitor
b. Subjects with unknown TP53 mutational status will be enrolled until the group of approximately 10 subjects without TP53 mutation or until all the planned subjects with TP53 mutation are enrolled as determined by the medical monitor
Part C2
a.Subjects with known BRCA1/BRCA2 germline mutations, either determined and documented prior to Screening, or determined during Screening. Subjects with unknown BRCA1/BRCA2 status may be enrolled.
b.Subjects who are documented to be non-basaloid subtype using molecular profiling assay (e.g. PAM50 assay) prior to Screening
c.Subjects with unknown BRCA1/BRCA2 or basaloid subtype status will be enrolled until the number of enrolled subjects is approximately 40. If approximately 40 subjects have been enrolled and a minimum of 30 subjects who are basaloid positive and BRCA1/BRCA2 germline wild-type have not been enrolled, the basaloid subtype and BRCA status assay will be required at Screening to exclude subjects who are basaloid negative or have BRCA1/BRCA2 germline mutations.
4.Unresolved toxicity of CTCAE Grade 2 or greater from previous anti-cancer therapy or radiotherapy, excluding:
a.Alopecia, anemia or leukopenia or other toxicities that in the opinion of the investigator and the sponsor should not exclude the subject
5.History of spinal cord compression or brain metastases. Any history of leptomeningeal metastases.
6.Female subjects who are already pregnant or lactating, or plan
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method