Clinical Trials /

Rucaparib MAintenance After Bevacizumab Maintenance Following Carboplatin Based First Line Chemotherapy in Ovarian Cancer Patients

NCT04227522

Description:

MAMOC is a multicenter, randomized, placebo controlled, double blind study including BRCA negative patients with histologically confirmed, advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) high grade serous or high grade endometrioid (based on local histopathological findings) ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary in first line therapy.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Rucaparib MAintenance After Bevacizumab Maintenance Following Carboplatin Based First Line Chemotherapy in Ovarian Cancer Patients
  • Official Title: Rucaparib MAintenance After Bevacizumab Maintenance Following Carboplatin Based First Line Chemotherapy in Ovarian Cancer Patients

Clinical Trial IDs

  • ORG STUDY ID: NOGGO ov42
  • NCT ID: NCT04227522

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Cancer
  • Clear Cell Carcinoma

Interventions

DrugSynonymsArms
RucaparibArm A (Rucaparib)
PlacebosArm B (Placebo)

Purpose

MAMOC is a multicenter, randomized, placebo controlled, double blind study including BRCA negative patients with histologically confirmed, advanced (FIGO stage IIIA, IIIB, IIIC, or IV of the 2014 FIGO classification) high grade serous or high grade endometrioid (based on local histopathological findings) ovarian cancer, fallopian tube cancer, primary peritoneal cancer and clear cell carcinoma of the ovary in first line therapy.

Detailed Description

      The main scope of this trial is to determine progression free survival in patients treated
      with Rucaparib as maintenance therapy vs. Placebo after receiving Bevacizumab for 12 to 15
      months.

      Patients will be stratified according to time point of surgery (adjuvant vs. neoadjuvant),
      result of surgery (tumor free vs. not tumor free resection), study site and response
      (complete response (CR) vs. partial response (PR)/SD) and randomized 2:1 to receive either
      Rucaparib (Arm A) or Placebo (Arm B).

      In both of the arms, tumor assessments (CT or MRI) are performed before randomization, and
      every 12 weeks thereafter.

      During treatment, clinical visits (blood cell counts, detection of toxicity) occur every 4
      weeks. Physical examinations and tumor assessments will take place every 12 weeks. Safety
      will be monitored continuously by careful monitoring of all adverse events (AEs) and serious
      adverse events (SAEs).

      About 30 sites in Germany will participate in this study to recruit 190 patients in 24
      months.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (Rucaparib)ExperimentalRucaparib treatment (starting dose 600 mg) after receiving Bevacizumab for 12 to 15 months. Cycles continue until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria.
  • Rucaparib
Arm B (Placebo)Placebo ComparatorPlacebo treatment after receiving Bevacizumab for 12 to 15 months. Cycles continue until disease progression and/or death, unacceptable adverse event/s, patient and/or investigator decision, other protocol stopping criteria.
  • Placebos

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent and obtained from the subject prior to performing any
             protocol-related procedures, including screening evaluations.

          2. Age ≥ 18.

          3. Patients with histologically confirmed, advanced (FIGO stage IIIA, IIIB, IIIC, or IV
             of the 2014 FIGO classification) serous or high grade endometrioid (based on local
             histopathological findings) ovarian cancer, fallopian tube cancer, primary peritoneal
             cancer and clear cell carcinoma of the ovary in first line therapy.

          4. Availability of archival tumor tissue for central next-generation sequencing (NGS)
             Analysis and no Detection BRCA mutation (BRCAnegative).

          5. Treatment with Bevacizumab for 12 to 15 months, independent of dosage.

          6. Patients who have completed first line platinum-taxane chemotherapy and at least
             stable disease after treatment with Bevacizumab before randomization.

          7. Patients must be randomized at least 3 weeks and no more than 9 weeks after their last
             dose of Bevacizumab (last dose is the day of the last infusion) and all major
             toxicities from the previous chemotherapy must have resolved to CTCAE grade 1 or
             better (except alopecia and peripheral neuropathy).

          8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          9. Patients must have normal organ and bone marrow function:

               1. Hemoglobin ≥ 10.0 g/dL independent of transfusion ≤ 14 days prior to Screening
                  hemoglobin assessment

               2. Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L

               3. Platelet count ≥ 100 x 109 /L

               4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); < 2 × ULN if
                  hyperbilirubinemia is due to Gilbert's syndrome

               5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT))
                  and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT))
                  ≤3 x ULN, unless liver metastases are present in which case they must be ≤ 5 x
                  ULN

               6. Serum creatinine ≤ 1.5 x institutional ULN and creatinine clearance > 30 mL/min

               7. Patients not receiving anticoagulant medication who have an International
                  Normalized Ratio (INR) ≤1.5 and an Activated ProThrombin Time (aPTT) ≤1.5 x ULN.

         10. Postmenopausal or evidence of non-childbearing status for women of childbearing
             potential prior to the first dose of study treatment. Female patients of childbearing
             potential must have a negative serum pregnancy test result ≤3 days prior to
             administration of the first dose of rucaparib.

        Patients are considered to be of childbearing potential unless 1 of the following applies:

          1. Considered to be permanently sterile. Permanent sterilization includes hysterectomy,
             bilateral salpingectomy, and/or bilateral oophorectomy; or

          2. Is postmenopausal, defined as no menses for at least 12 months without an alternative
             medical cause. A high follicle-stimulating hormone (FSH) level consistently in the
             postmenopausal range (30 milli International Units/milliliter (mIU/mL) or higher) may
             be used to confirm a postmenopausal state in women not using hormonal contraception or
             hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a
             single FSH measurement is insufficient to confirm a postmenopausal state.

        Female patients of reproductive potential must practice highly effective methods (failure
        rate < 1% per year) of contraception with their partners, if of reproductive potential,
        during treatment and for 6 months following the last dose of rucaparib or longer if
        requested by local authorities. Highly effective contraception includes: Ongoing use of
        progesterone only injectable or implantable contraceptives; Placement of an intrauterine
        device (IUD) or intrauterine system (IUS); Bilateral tubal occlusion; Sexual abstinence as
        defined as complete or true abstinence, acceptable only when it is the usual and preferred
        lifestyle of the patient; periodic abstinence (eg, calendar, symptothermal, post-ovulation
        methods) is not acceptable; or Sterilization of the male partner, with appropriate
        post-vasectomy documentation of absence of sperm in ejaculate.

        Exclusion Criteria:

          1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ
             cell tumors) and Ovarian tumors of low malignant potential (e.g. borderline tumors),
             or mucinous carcinoma.

          2. Patients with myelodysplastic syndrome/acute myeloid leukemia history.

          3. Patients receiving radiotherapy within 6 weeks prior to study treatment.

          4. Major surgery within 4 weeks of starting study treatment and patients must have
             recovered from any effects of any major surgery.

          5. Previous allogeneic bone marrow transplant.

          6. Administration of other simultaneous chemotherapy drugs, any other anti-cancer therapy
             or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial
             treatment period (hormonal replacement therapy is permitted as are steroidal
             antiemetics).

          7. Clinically significant (e.g. active) cardiovascular disease.

          8. Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or
             Sub-Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.

          9. History or evidence of hemorrhagic disorders within 6 months prior to randomization.

         10. Evidence of bleeding diathesis or significant coagulopathy (in the absence of
             coagulation).

         11. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI
             of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected
             brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in
             case of suspected spinal cord compression.

         12. History or evidence upon neurological examination of central nervous system (CNS)
             disease, unless adequately treated with standard medical therapy (e.g. uncontrolled
             seizures).

         13. Significant traumatic injury during 4 weeks prior to randomization.

         14. Non-healing wound, active ulcer or bone fracture. Patients with granulating incisions
             healing by secondary intention with no evidence of facial dehiscence or infection are
             eligible but require 3 weekly wound examinations.

         15. Current, clinically relevant bowel obstruction, including sub-occlusive disease,
             related to underlying disease.

         16. Evidence of any other disease, metabolic dysfunction, physical examination finding or
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or puts the patient at high risk
             for treatment related complications.

         17. Pregnant or lactating women, women of child-bearing potential who do not agree to the
             usage of highly effective contraception methods (see inclusion criteria).

         18. Participation in another clinical study with an investigational product immediately
             prior to randomization.

         19. Patients unable to swallow orally administered medication and patients with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

         20. Patients with a known hypersensitivity to Rucaparib or any of the recipients of the
             product.

         21. Known human immunodeficiency virus (HIV) or acquired immunodeficiency Syndrome
             (AIDS)-related illness, or history of chronic hepatitis B or C.

         22. Other active malignancy requiring treatment.

         23. Patient who might be dependent on the sponsor, Clinical Research Organization (CRO),
             site or the investigator.

         24. Patient who has been incarcerated or involuntarily institutionalized by court order or
             by the authorities § 40 Abs. 1 S. 3 Nr. 4 Arzneimittelgesetz (AMG).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:48 months
Safety Issue:
Description:time from randomization until disease progression or death

Secondary Outcome Measures

Measure:Progression free survival 2 (PFS2)
Time Frame:48 months
Safety Issue:
Description:time from randomization to second progression or death
Measure:Quality of Life (QoL) 1
Time Frame:48 months
Safety Issue:
Description:Patients are asked to answer the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Responses of questions 1-28 are based on a 4-point scale (1=not at all; 4=Very much), with a higher score indicating a high degree of symptomatology and must therefore be assessed negatively. Responses of questions 29 and 30 are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status.
Measure:Quality of Life 2
Time Frame:48 months
Safety Issue:
Description:Patients are asked to answer the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28). Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better symptoms.
Measure:Quality of Life/ Global health status 3
Time Frame:48 months
Safety Issue:
Description:Patients are asked to answer the short version of the SF-36 Health Survey (SF-12). The questionnaire contains a total of 12 questions with different response options. For questions 1, 8 and 12 there are 5 (1=excellent, 5=bad), for question 2-3 there are 3 (1=yes, very restricted, 3=no, not restricted at all) and for questions 9-11 there are 6 response options (1= always, 6 = never). Questions 4-7 can be answered with "Yes" or "No".
Measure:Quality of Life 4
Time Frame:48 months
Safety Issue:
Description:Patients are asked to answer the questionnaire Fatigue Symptom Inventory (FSI). Responses are based on a 10 point grading scale (0=not at all tired/ exhausted; 10=completely tired/ exhausted), with a lower score indicating a lower symptomatology of fatigue.
Measure:Quality of Life 5
Time Frame:48 months
Safety Issue:
Description:Patients are asked to answer the Everyday Memory Questionnaire. Responses are based on a 5-point scale (1=occasionally; 5=very often), with a lower score indicating a better performance on memory associated Everyday activities.
Measure:Quality of Life 6
Time Frame:48 months
Safety Issue:
Description:Patients are asked to answer a custom form of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute (NCI PRO-CTCAE™) Version 1.0. The frequency and strength of symptoms is queried. There are 5 possible answers: "not at all", "a little", "moderate", "quite", "very".
Measure:Determination of time to next medical intervention
Time Frame:48 months
Safety Issue:
Description:(e.g. bowel obstruction, Ascites puncture)
Measure:Time to next subsequent therapy
Time Frame:48 months
Safety Issue:
Description:e.g. chemotherapy
Measure:Number of participants with treatment-related adverse events and/or serious adverse events as assessed by CTCAE v4.03
Time Frame:48 months
Safety Issue:
Description:AEs/SAEs
Measure:Overall survival (OS)
Time Frame:72 months
Safety Issue:
Description:defined as time from Randomization to death by any cause

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:North Eastern German Society of Gynaecological Oncology

Trial Keywords

  • Rucaparib
  • maintenance therapy
  • Bevacizumab
  • Ovarian Cancer
  • BRCA negative

Last Updated

March 2, 2020