Trial Title:
RP-6306 in Patients With Advanced Cancer
NCT ID:
NCT05605509
Condition:
Advanced Cancer
Conditions: Official terms:
Neoplasms
Gemcitabine
Trastuzumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
RP-6306
Description:
Dose and schedule will be assigned at enrolment
Arm group label:
RP-6306 + FOLFIRI
Arm group label:
RP-6306 + Gemcitabine
Arm group label:
RP-6306 + Trastuzumab
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Dose and schedule will be assigned at enrolment
Arm group label:
RP-6306 + Gemcitabine
Intervention type:
Drug
Intervention name:
FOLFIRI Protocol
Description:
Irinotecan Leucovorin FU
Arm group label:
RP-6306 + FOLFIRI
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
standard doses q3weekly
Arm group label:
RP-6306 + Trastuzumab
Summary:
This study is being done to answer the following questions:
- Is the new drug, RP-6306, safe to use, and what effects does it have on cancer when
given with standard treatment?
- If there are specific biomarkers, do patients have an improved response to treatment
compared to those without the biomarker?
This study is being done to find out if this approach is better or worse than the usual
approach for this type of cancer. The usual approach is defined as care most people get
for this type of cancer.
Detailed description:
RP-6306 is a PKMYT1 inhibitor. PKMYT1 protein kinase negatively regulates CDK1 via
phosphorylation of threonine 14 (Thr14) and sequestration in the cytoplasm. RP-6306 has
shown single-agent anti-tumour efficacy in several xenograft models with amplified CCNE1
in a dose-dependent manner. RP-6306 has synergistic effects in combination with
gemcitabine in CCNE1-amplified/overexpressing models in vitro and in vivo
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically confirmed cancer, that is
advanced/metastatic/recurrent or unresectable, for which no curative therapy exists,
and be eligible for one or more of the open cohorts
- All patients must have a formalin fixed paraffin embedded tissue block (from primary
or metastatic tumour) available and must have provided informed consent for the
release of the block
- Presence of clinically and/or radiologically documented disease. All radiology
studies must be performed within 21 days prior to enrollment
- Patients must be ≥ 18 years of age
- Patients must have an ECOG performance status of 0 or 1
- Patients must have a life expectancy of 3 months or longer
- Abs neutrophils ≥ 1.5 x 10^9/L; Platelets ≥ 100 x 10^9/L
- Bilirubin ≤ 1.5 x UNL; AST ≤2.5 x UNL; ALT ≤ 5.0 x UNL; Serum creatinine ≤ 1.5 x
UNL; Creatinine clearance ≥ 50 mL/min
- Patients must be able to swallow oral medications and have no known gastrointestinal
disorders that may interfere with absorption (such as malabsorption)
- Patients must have had recovered (to at least grade 0 or 1) from all reversible
toxicity related to prior chemotherapy or systemic therapy and have adequate washout
longest of one of the following: two weeks; 5 half-lives for investigational agents;
standard cycle length of standard therapies.
- Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks)
have elapsed between the last dose of radiation and date of enrollment. Exceptions
may be made for low-dose, non-myelosuppressive radiotherapy after consultation with
CCTG. Concurrent radiotherapy is not permitted
- Previous surgery is permitted provided that a minimum of 21 days (3 weeks) have
elapsed between any major surgery and date of enrollment, and that wound healing has
occurred
- Patient consent must be appropriately obtained in accordance with applicable local
and regulatory requirements. Each patient must sign a consent form prior to
screening (if applicable)/enrollment in the trial to document their willingness to
participate
- Protocol treatment is to begin within 2 working days of patient enrollment
- Patients must be accessible for treatment and follow-up. Patients enrolled on this
trial must be treated and followed at the participating centre
- Women/men of childbearing potential must have agreed to use a highly effective
contraceptive method.
Cohort-Specific Eligibility Criteria
Cohort A: Endometrial Cancer
- Patients must have histologically confirmed diagnosis of high-grade serous
endometrial cancer, that is advanced/metastatic/recurrent or unresectable, for which
no curative therapy exists.
- Patients must have abnormal TP53 on IHC/genomic testing*.
- Patients must have had at least 1 prior line of platinum-based chemotherapy in any
setting but may not have received prior gemcitabine therapy.
Cohort B1: HGSOC
- Patients must have a histologically confirmed diagnosis of high-grade serous ovarian
cancer/fallopian tube/primary peritoneal carcinoma (HGSOC) which is
platinum-refractory per standard definitions.
- Patients must have abnormal TP53 on IHC/genomic testing*.
- Platinum refractory disease refers to patients with progressive disease on
first-line platinum-based chemotherapy or progressive disease within 12 weeks of the
last dose of first-line platinum-based therapy [Gynecologic Cancer Intergroup
Consensus Recommendations 2022].
Cohort B2: Uterine Carcinosarcoma
- Patients must have had at least 1 prior line of platinum-based chemotherapy but may
not have received prior gemcitabine therapy.
- Patients must have abnormal TP53 on IHC/genomic testing*.
Cohort B3: Ovarian Carcinosarcoma
- Patients must have had at least 1 prior line of platinum-based chemotherapy but may
not have received prior gemcitabine therapy.
- Patients must have abnormal TP53 on IHC/genomic testing*.
Cohort B4: TNBC
- Patients must have had at least 2 prior lines of therapy in the advanced setting.
- Patients may not have received prior gemcitabine.
Cohort B5: PDAC
- Patients must have prior FOLFIRINOX either in the palliative/advanced setting or
have relapsed within 6 months of completing adjuvant or neoadjuvant FOLFIRINOX.
- Patients may not have received prior gemcitabine.
- Patients must have abnormal TP53 on IHC/genomic testing*.
Cohort B6: NSCLC
- Patients must have received standard therapies including platinum combination
chemotherapy, standard salvage chemotherapy, immunotherapy, and targeted therapies
as applicable.
- Patients may not have received prior gemcitabine.
Cohort C1: Colorectal Cancer
- Patients must have histologically confirmed diagnosis of colorectal cancer, that is
advanced/metastatic/recurrent or unresectable, for which no curative therapy exists.
- Patients must have both a RAS mutation (KRAS) and a TP53 mutation based on local
testing*.
- Patients must be eligible to receive FOLFIRI; patients homozygous for UGT1A1*28
allele are not eligible
- Patients must have had at least 1 prior line of cytotoxic chemotherapy with FOLFOX,
either as:
- 1st line therapy for metastatic disease, or
- recurrence within 6 months of completion of adjuvant FOLFOX.
Cohort D1: HER-2+ Gastroesophageal Cancer
- Patients must have histologically confirmed diagnosis of gastroesophageal cancer,
that is advanced/metastatic/recurrent or unresectable, for which no curative therapy
exists.
- Tumour must be HER-2+ (IHC 3+, or FISH+) and have CCNE1 amplification
Exclusion Criteria:
- Patients with a history of other malignancies, except: adequately treated
non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other
solid tumours curatively treated with no evidence of disease for > 2 years and which
do not require ongoing treatment
- Patients with active or uncontrolled infections or with serious illnesses or medical
conditions which would not permit the patient to be managed according to the
protocol
- Patients are not eligible if they have a known hypersensitivity to the study drug(s)
or their components
- Prior use of WEE1 inhibitor or PKMYT1 inhibitor
- Patients with significant cardiac (including uncontrolled hypertension) or pulmonary
disease, or active CNS disease or infection. Patients should have a LVEF ≥ 50%.
- Patients may not receive concurrent treatment with other anti-cancer therapy (other
than bone-targeted therapy, if already taking and stable) or investigational agents
while on protocol therapy
- Patients who have received growth factors within 28 days prior to initiation of
dosing of RP-6306 or who will require treatment with growth factors throughout the
duration of the trial
- Pregnant or breastfeeding women
- Patients with history of central nervous system metastases or spinal cord
compression unless they have received definitive treatment, are clinically stable
and do not require corticosteroids
- Patients with any medical condition that would impair the administration of oral
agents including significant bowel resection, inflammatory bowel disease or
uncontrolled nausea or vomiting
- Patients who cannot discontinue the use of proton pump inhibitors, strong CYP3A
inhibitors or inducers.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
BCCA - Kelowna
Address:
City:
Kelowna
Zip:
V1Y 5L3
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Guillermo Martos
Phone:
250 712-3900
Facility:
Name:
BCCA - Vancouver
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Yvette Drew
Phone:
604 877-6000
Phone ext:
4831
Facility:
Name:
Juravinski Cancer Centre at Hamilton Health Sciences
Address:
City:
Hamilton
Zip:
L8V 5C2
Country:
Canada
Status:
Not yet recruiting
Contact:
Last name:
Rosalyn Anne Juergens
Phone:
905 387-9711
Phone ext:
64604
Facility:
Name:
Kingston Health Sciences Centre
Address:
City:
Kingston
Zip:
K7L 2V7
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Andrew Robinson
Phone:
613 549-6666
Phone ext:
8104
Facility:
Name:
Verspeeten Family Cancer Centre
Address:
City:
London
Zip:
N6A 5W9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Stephen Welch
Phone:
519 685-8640
Facility:
Name:
Ottawa Hospital Research Institute
Address:
City:
Ottawa
Zip:
K1H 8L6
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Moira Rushton
Facility:
Name:
University Health Network
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Stephanie Lheureux
Phone:
416 946-4501
Phone ext:
2415
Start date:
May 24, 2023
Completion date:
June 2025
Lead sponsor:
Agency:
Canadian Cancer Trials Group
Agency class:
Other
Collaborator:
Agency:
Repare Therapeutics
Agency class:
Industry
Source:
Canadian Cancer Trials Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05605509
