Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors

  • STATUS
    Recruiting
  • End date
    Apr 23, 2025
  • participants needed
    1000
  • sponsor
    Gustave Roussy, Cancer Campus, Grand Paris
Updated on 23 January 2021
platelet count
cancer
measurable disease
international normalized ratio
metastasis
neutrophil count
liver metastasis
blood transfusion
aptt
solid tumor
parp inhibitor

Summary

The primary objective of the trial is to evaluate the antitumor activity of atezolizumab and rucaparib in patients with selected advanced solid tumors as measured by the Overall Response Rate

Details
Condition Solid Tumors, Solid Tumor, Solid Neoplasm, Solid Tumour
Treatment Atezolizumab, rucaparib
Clinical Study IdentifierNCT04276376
SponsorGustave Roussy, Cancer Campus, Grand Paris
Last Modified on23 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have Solid Tumor?
Do you have any of these conditions: Solid Tumor or Solid Tumors or Solid Tumour or Solid Neoplasm?
Signed informed consent form
Age 18 years
Patients must have histologically or cytologically confirmed progressive metastatic or recurrent solid tumor (as defined below for each tumor type). Diagnosis must be stated in a pathology report and confirmed by the investigator
Representative archival formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or 20 freshly cut and unstained slides, with an associated pathology report, for ancillary studies and central testing, is mandatory for all cohorts. In all cases, recovery of the most recent tumor block or biopsy is encouraged and tumor tissue has to date back from less than 3 years ago. If tumor tissue is more than 3 years old, a fresh tumor biopsy is mandatory for cohorts 1, 2 and 4
Specificities for Cohorts 1A-D
For patients with DNA repair gene mutation already identified by local testing, mutational testing must have been done less than one year prior to inclusion in the trial (i.e. signing of informed consent). Tumor block should correspond to the one that has been used for the original testing. If more recent blocks are available, these should be provided for ancillary studies, and the presence of the mutation of interest should be confirmed on these
If no archival tissue is available or if tumor tissue is more than 3 years old, feasibility of a fresh tumor biopsy at baseline (C0D1 pre-dose) should be ensured and mutation confirmed on that tissue for cohorts 1A, 1B and 1D. Only tissue from core needle, punch or excisional biopsy sample collection will be accepted. Other methods such as fine-needle aspiration, brushing, bone tissue or lavage samples are not acceptable
Bone biopsies are allowed for mCRPC (cohort 1C), if sufficient tumor cellularity can be achieved
Specificity for cohort 3
If no archival tumor biopsy is available, a new fresh biopsy should be done prior to treatment start (C0D1 pre-dose) whenever feasible; otherwise, any archival tumor tissue will be accepted
Core or excisional biopsy from soft tissue or a bone biopsy is required from a site not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed; other exceptions may be considered after Sponsor consultation)
Measurable disease, defined as
For the non-prostate cohorts: At least one lesion, not previously irradiated, measurable according to RECIST v1.1 as 10 mm in the longest diameter (except lymph nodes which must have short axis 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and suitable for repeated assessment
For prostate cohorts: At least one lesion, not previously irradiated, measurable according to RECIST v1.1 and / or bone scan measurable disease (Cf inclusion criteria 4) and / or measurable disease according to Prostate Cancer Working Group Criteria 3 (PCWG3) 7. Agreement of the patient to sign the genetic analysis consent form for access to plasma samples for ctDNA analysis
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration from registration date
Estimated life expectancy of greater than 12 weeks. 10. Adequate hematologic and organ function, defined by the following laboratory results obtained within 3 days prior to the first study treatment (Cycle 0 Day 1)
Absolute neutrophil count (ANC) 1500 cells/L (without granulocyte colony-stimulating factor support within 2 weeks before cycle 0 day 1)
Platelet count 100.000/L (without transfusion within 2 weeks before Cycle 0 Day 1)
Hemoglobin 9g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion)
Total bilirubin 1.5 ULN (subjects with documented/suspected Gilbert's disease or liver metastases may be enrolled with bilirubin 3 ULN)
Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) 2.5 x upper normal limit (ULN) or 5 ULN in case of liver metastases
Albumin 28g/L
Serum creatinine 1.5 x ULN or creatinine clearance 40mL/min (according to Cockroft and Gault formula)
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) 1.5 x ULN. This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular weight heparin or warfarin) should be on stable dose
Women of childbearing potential must have a negative serum -HCG pregnancy test within 7 days prior to the administration of the first study treatment 12. Sexually active women of childbearing potential must agree to use a highly effective method of contraception << supplemented by a barrier method >>, or to abstain from sexual activity during the study and for at least 6 months after the last study treatment administration
Sexually active males patients must agree to use condom during the study and for at least 6 months after the last study treatment administration. Also, it is recommended their women of childbearing potential partner use a highly effective method of contraception
A woman is considered of childbearing potential following menarche and until
becoming post-menopausal ( 12 months of non-therapy-induced amenorrhea) unless
permanently sterile. Permanent sterilization methods include hysterectomy
bilateral oophorectomy and bilateral salpingectomy. A highly effective birth
control method is a one which can achieve a failure rate of less than 1% per
year when used consistently and correctly. Such methods include: combined
(estrogen and progesterone containing) hormonal contraception; progestogen-
only hormonal contraception associated with inhibition of ovulation
intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
bilateral tubal occlusion; vasectomized partner (on the understanding that
this is the only one partner during the whole study duration), and sexual
abstinence during the entire period of risk associated with study treatment
To prevent the risk of interaction between the study drug and hormonal
contraceptives, hormonal contraceptives should be supplemented with a barrier
method (preferably male condom). Following methods are considered as
unacceptable methods (non-exhaustive list): periodic abstinence (calendar
symptothermal, post-ovulation methods) and withdrawal (coitus interruptus)
\. Patient should understand, sign, and date the written informed consent
form prior to any protocol-specific procedures performed
\. Patient should be able and willing to comply with study visits and
procedures as per protocol
\. Patients must be affiliated to a social security system or beneficiary of
an equivalent system

Exclusion Criteria

Participation in another clinical study with an investigational product during the last 4 weeks (excepting non-interventional clinical studies) and while on study treatment
Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy (excepted androgen deprivation therapy by LHRH agonists for prostate cancer patients), targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) 28 days prior to the first dose of study drug, or five half lives of the previous agent, whichever is the shorter
Prior radiation therapy within 2 weeks prior to Cycle 0 Day 1
History of another primary malignancy within 5 years prior to Cycle 0 Day 1 except
for
Malignancy treated with curative intent and with no known active disease 5 years before the first dose of study drug and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease (eg, carcinoma in situ of the cervix, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent)
Treatment with systemic corticosteroids or other immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents) within 2 weeks prior to Cycle 0 Day 1, or anticipated requirements for systemic immunosuppressive medications during the trial
The use of inhaled corticosteroids for chronic obstructive pulmonary
disease, mineralocorticoids for patients with orthostatic hypotension, low-
dose supplemental corticosteroids for adrenocortical insufficiency and topical
steroids for cutaneous diseases are allowed
\. Acute toxicities from previous therapies that have not resolved to Grade
with the exception of alopecia
\. Any prior Grade 3 immune-related adverse event (irAE) while receiving any
previous immunotherapy agent, or any unresolved irAE > Grade 1
\. History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins
\. Known hypersensitivity or allergy to biopharmaceuticals produced in
Chinese hamster ovary cells or to any component of the atezolizumab
formulation
\. History of autoimmune/immune mediated inflammatory disease, including but
not limited to colitis, pneumonitis, hepatitis, hypophysitis, nephritis
hyperthyroidism, systemic lupus erythematous, rheumatoid arthritis
inflammatory bowel disease, Wegener's granulomatosis, Sjgren's syndrome
Guillain-Barr syndrome, vasculitis, or glomerulonephritis excepted stable
hypothyroidism or stable Type 1 diabetes mellitus
\. Active or prior documented inflammatory bowel disease (e.g. Crohn's
disease, ulcerative colitis)
\. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-
induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans
cryptogenic organizing pneumonia), or evidence of active pneumonitis on
screening chest CT scan - History of radiation pneumonitis in the radiation
field (fibrosis) is permitted
\. History of allogeneic organ transplant or prior bone marrow
transplantation of double umbilical cord blood transplantation
\. Uncontrolled intercurrent illness including, but not limited to
ongoing or active infection or severe infection requiring hospitalization or IV antibiotics within 2 weeks of starting treatment (with the exception of prophylactic antibiotics)
symptomatic congestive heart failure > NYHA II, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, pericardial effusion
active peptic ulcer disease or gastritis
active bleeding diatheses. 15. Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. 16. Patients with known left ventricular ejection fraction (LVEF) < 40%; patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable cardiologic treatment. 17. Known positive test for HIV. 18. Patients with active hepatitis B (defined as positive HBsAg test at screening) or hepatitis C (HCV). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen anti-HBc) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 19. Active tuberculosis. 20. Administration of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study. - Influenza vaccination should be given during influenza season only (example: approximately October to March in the Northern Hemisphere). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study treatment or within 5 months after the last dose of atezolizumab. 21. Major surgical procedure within 28 days prior to Cycle 0 Day 1 or anticipation of need for a major surgical procedure during the course of the study. 22. Uncontrolled tumor-related pain: patients requiring pain medication must be on a stable regimen at study entry and symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrollment. 23. Uncontrolled effusion (pleural, pericardial or ascites) requiring recurrent drainage procedures (once a month or more frequently); patients with indwelling catheters (e.g. PleurX) are allowed. 24. Uncontrolled hypercalcemia (>1.5mmol/L ionized calcium or Ca > 12mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. 25. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history or clinically significant hypercalcemia are eligible 26. History of leptomeningeal disease
Symptomatic CNS metastasis or uncontrolled CNS metastasis, requiring increasing doses of steroids or stable dose of steroids > 10mg prednisone qd
Spinal cord compression without evidence that disease has been clinically stable for 2 weeks prior to Cycle 0 Day 1. 27. Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control. 28. Previous treatment with PARP inhibitors. 29. Concomitant use of strong inhibitors or inducers of CYP3A4 30. Treatment with systemic immunostimulatory agents (e.g. INF-a and IL-2) within 4 weeks prior to Cycle 0 Day 1. 31. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study result. 32. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving its consent
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