Clinical Trials /

Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel

NCT04449549

Description:

Background: People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing. Objective: To learn if nilotinib and paclitaxel will benefit people with rare cancers. Eligibility: People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors. Participants will repeat the screening tests during the study. Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle. Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have. Participants may have optional tumor biopsies. Participants can stay on the study until their disease gets worse or they have intolerable side effects. Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

Related Conditions:
  • Adenoid Cystic Carcinoma
  • Adrenal Cortex Carcinoma
  • Adrenal Gland Pheochromocytoma
  • Anal Carcinoma
  • Angiosarcoma
  • Bartholin Gland Transitional Cell Carcinoma
  • Basal Cell Carcinoma
  • Bile Duct Neoplasm
  • Bladder Adenocarcinoma
  • Bladder Squamous Cell Carcinoma
  • Bronchioloalveolar Carcinoma
  • Cervical Clear Cell Adenocarcinoma
  • Chordoma
  • Colon Squamous Cell Carcinoma
  • Desmoid-Type Fibromatosis
  • Endometrial Clear Cell Adenocarcinoma
  • Endometrial Transitional Cell Carcinoma
  • Esophageal Undifferentiated Carcinoma
  • Extragonadal Germ Cell Tumor
  • Extrahepatic Cholangiocarcinoma
  • Extramammary Paget Disease
  • Fallopian Tube Transitional Cell Carcinoma
  • Fibromyxoid Tumor
  • Gallbladder Carcinoma
  • Gastric Squamous Cell Carcinoma
  • Gastrointestinal Stromal Tumor
  • Gestational Trophoblastic Tumor
  • Infiltrating Renal Pelvis Urothelial Carcinoma, Sarcomatoid Variant
  • Intrahepatic Cholangiocarcinoma
  • Low-Grade Appendiceal Mucinous Neoplasm
  • Lung Sarcomatoid Carcinoma
  • Lymphoma
  • Malignant Adrenal Cortex Neoplasm
  • Malignant Apocrine Neoplasm
  • Malignant Giant Cell Neoplasm
  • Malignant Myoepithelioma
  • Malignant Neoplasm of Unknown Primary
  • Malignant Odontogenic Neoplasm
  • Malignant Ovarian Clear Cell Tumor
  • Malignant Peripheral Nerve Sheath Tumor
  • Merkel Cell Carcinoma
  • Metaplastic Breast Carcinoma
  • Nasal Cavity Carcinoma
  • Nasopharyngeal Carcinoma
  • Neuroendocrine Carcinoma
  • Neurofibromatosis Type 1
  • Olfactory Neuroblastoma
  • Ovarian Germ Cell Tumor
  • Ovarian Sarcoma
  • Ovarian Sex Cord Stromal Tumor
  • Ovarian Small Cell Carcinoma, Hypercalcemic Type
  • Ovarian Transitional Cell Carcinoma
  • PEComa
  • Pancreatic Acinar Cell Carcinoma
  • Pancreatic Mucinous-Cystic Neoplasm with an Associated Invasive Carcinoma
  • Pancreatic Neuroendocrine Carcinoma
  • Pancreatic Serous Cystadenocarcinoma
  • Papillary Renal Cell Carcinoma
  • Papillary Transitional Cell Carcinoma
  • Paraganglioma
  • Paranasal Sinus Carcinoma
  • Parathyroid Gland Carcinoma
  • Peritoneal Mesothelioma
  • Pituitary Gland Carcinoma
  • Pleomorphic Adenoma
  • Pleural Mesothelioma
  • Primary Peritoneal Transitional Cell Carcinoma
  • Prostate Small Cell Carcinoma
  • Rectal Squamous Cell Carcinoma
  • Renal Pelvis Adenocarcinoma
  • Renal Pelvis Squamous Cell Carcinoma
  • Salivary Gland Carcinoma
  • Sarcoma
  • Sarcomatoid Transitional Cell Carcinoma
  • Small Intestinal Adenocarcinoma
  • Squamous Cell Carcinoma of the Penis
  • Testicular Germ Cell Tumor
  • Thymic Carcinoma
  • Thyroid Gland Carcinoma
  • Trophoblastic Neoplasm
  • Undifferentiated Gastric Carcinoma
  • Ureter Adenocarcinoma
  • Ureter Squamous Cell Carcinoma
  • Uterine Corpus Carcinosarcoma
  • Uterine Corpus Leiomyosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel
  • Official Title: Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel

Clinical Trial IDs

  • ORG STUDY ID: 200121
  • SECONDARY ID: 20-C-0121
  • NCT ID: NCT04449549

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
Nilotinib1
Paclitaxel1

Purpose

Background: People with rare cancers often have limited treatment options. The biology of rare cancers is not well understood. Researchers want to find better treatments for these cancers. They want to test 2 drugs that, taken separately, have helped people with non-rare cancers. They want to see if these drugs together can make rare cancers shrink or stop growing. Objective: To learn if nilotinib and paclitaxel will benefit people with rare cancers. Eligibility: People age 18 and older who have a rare, advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: Participants will be screened with medical history and physical exam. They will have blood and urine tests. They will have a pregnancy test if needed. They will have an electrocardiogram to check their heart. They will have imaging scans to measure their tumors. Participants will repeat the screening tests during the study. Participants will receive nilotinib and paclitaxel. The drugs are given in 28-day cycles. Nilotinib is a capsule taken by mouth twice a day. Paclitaxel will be given intravenously by peripheral line or central line once a week for the first 3 weeks of each cycle. Participants will keep a medicine diary. They will track when they take the study drugs and any side effects they may have. Participants may have optional tumor biopsies. Participants can stay on the study until their disease gets worse or they have intolerable side effects. Participants will have a follow-up phone call about 30 days after taking the last dose of study drugs.

Detailed Description

      Background:

        -  Rare tumors constitute a heterogeneous group of cancers associated with limited
           treatment options and poor outcomes. Due to their rarity, there are few good models for
           these diseases to support preclinical evaluation of new anticancer agents. To address
           these challenges, DCTD s Patient-Derived Models Repository (PDMR) is generating
           patient-derived xenograft models of adult and pediatric rare cancers and has screened
           combinations of approved and investigational anticancer agents in these models.

        -  Based on preclinical activity, drug combinations are being tested in patients with rare
           cancers in a series of connected Phase 2 clinical trials (Rapid Analysis and Response
           Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors [RARE CANCER]);
           responses may trigger further evaluation of a treatment in that rare cancer type to
           further evaluate response rate and mechanism-of-action. Patients who progress will be
           offered another RARE CANCER trial.

        -  The agents used in this trial are the BCR-Abl kinase inhibitor nilotinib and the
           anti-tubulin agent paclitaxel, which showed greater than additive activity in
           combination in preclinical xenograft models and subsequently demonstrated clinical
           efficacy (including partial responses) in patients with solid tumors on the Phase 1
           trial 15-C-0086 (NCT02379416).

      Primary Objectives:

      - To evaluate the proportion of patients with advanced rare cancers who have objective
      responses (OR) to treatment with nilotinib and paclitaxel

      Exploratory Objectives:

        -  To evaluate the proportion of patients alive and progression free at 6 months on study
           agents

        -  To identify genomic and transcriptomic determinants of response and resistance in tumor
           biopsy specimens

        -  To examine genomic alterations in circulating tumor DNA (ctDNA) and circulating tumor
           cells (CTCs) that may be associated with response or resistance

        -  To evaluate the pharmacodynamic effects of the combination on biomarkers of cell death
           and epithelial-to-mesenchymal transition in tumor tissue and CTCs

      Eligibility:

        -  Study participants must have a histologically confirmed solid tumor meeting the RARECARE
           definition of rare tumor that has progressed on standard therapy known to prolong
           survival or for which no standard treatment options exist

        -  Age >= 18

        -  No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study
           (6 weeks for nitrosoureas and mitomycin C) or 5 half-lives of the agent, whichever is
           shorter; toxicity from prior treatment must have recovered to eligibility levels.

        -  Adequate organ function; performance status ECOG 0-2

      Study Design:

        -  Nilotinib will be administered at 300 mg orally BID and paclitaxel will be administered
           IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles.

        -  A single-stage design will be used with a target accrual of 30 eligible patients. If at
           least 4/30 patients experience an objective response (PR or CR by RECIST 1.1), the
           combination of nilotinib and paclitaxel will be considered promising. The accrual
           ceiling is 34 patients.
    

Trial Arms

NameTypeDescriptionInterventions
1ExperimentalNilotinib will be administered at 300 mg orally BID; Paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28- day cycles.
  • Nilotinib
  • Paclitaxel

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Patients must have histologically confirmed rare solid tumors that have progressed on
             standard therapy known to prolong survival or for which no standard treatment options
             exist. The list of eligible rare tumors can be found below**; other rare tumor types
             may be acceptable at the discretion of the PI.

          -  Age >= 18 years.

          -  ECOG performance status <= 2.

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count >=1,500/mcL

               -  Platelets >=100,000/mcL

               -  Total bilirubin <=1.5 X institutional ULN

               -  AST(SGOT)/ALT(SGPT) <=3 X institutional upper limit of normal; <= 5.0 x ULN in
                  patients with liver metastases

               -  creatinine <=1.5 X institutional ULN OR

               -  creatinine clearance >=60 mL/min/1.73 m^2 for patients with creatinine levels
                  >1.5 mg/dL

          -  Nilotinib and paclitaxel have both been assigned to pregnancy category D by the FDA.
             For this reason, women of child-bearing potential and men must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation and for at least 3 months after
             dosing with study drugs ceases. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 3 months after completion of study drug administration.

          -  Patients must have completed radiation therapy or major surgery >= 3 weeks, or
             biologic therapy or chemotherapy >= 5 half-lives or 3 weeks, whichever is shorter (6
             weeks for nitrosoureas and mitomycin C) prior to entering the study. Patients must be
             >= 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent
             study and be >= 1 week from palliative radiation therapy (patients on study may be
             eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy
             at the PI s discretion). Patients must have recovered to eligibility levels from prior
             toxicity or adverse events. Treatment with bisphosphonates is permitted.

          -  Biopsies are optional on this study. In lieu of baseline biopsies, patients are
             encouraged to submit at registration archival tumor biopsy tissue from a previous
             research study or medical care providing it meets the minimum collection and
             preservations requirements outlined in Section 5.1.3.4. Criteria for the submission of
             archival tissue are:

               -  Tissue must have been collected within 3 months prior to registration.

               -  Patient must not have received any intervening therapy for their cancer since the
                  collection of the tumor sample.

                    -  Rare Tumor Eligibility List

                         1. Epithelial tumors of nasal cavity, sinuses, nasopharynx

                         2. Epithelial tumors of major salivary glands

                         3. Salivary gland type tumors of head and neck, lip, esophagus, stomach,
                            trachea and lung, breast and other location

                         4. Undifferentiated carcinoma of gastrointestinal (GI) tract

                         5. Adenocarcinoma with variants of small intestine

                         6. Squamous cell carcinoma with variants of GI tract (stomach small
                            intestine, colon, rectum, pancreas)

                         7. Fibromixoma and low-grade mucinous adenocarcinoma (pseudomixoma
                            peritonei) of the appendix and ovary

                         8. Rare Pancreatic tumors including acinar cell carcinoma, mucinous
                            cystadenocarcinoma or serous cystadenocarcinoma

                         9. Intrahepatic cholangiocarcinoma

                        10. Extrahepatic cholangiocarcinoma and bile duct tumors

                        11. Sarcomatoid carcinoma of lung

                        12. Bronchoalveolar carcinoma lung (a.k.a. adenocarcinoma in situ,
                            minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma,
                            or invasive mucinous adenocarcinoma)

                        13. Non-epithelial tumors of the ovary

                        14. Trophoblastic tumor

                        15. Transitional cell carcinoma other than that of the renal, pelvis,
                            ureter, or bladder

                        16. Cell tumor of the testes and extragonadal germ tumors

                        17. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma
                            with variants of penis

                        18. Squamous cell carcinoma variants of the genitourinary (GU) system

                        19. Spindle cell carcinoma of kidney, pelvis, ureter

                        20. Adenocarcinoma with variants of GU system (excluding prostate cancer)

                        21. Odontogenic malignant tumors

                        22. Pancreatic neuroendocrine tumor (PNET)

                        23. Neuroendocrine carcinoma including carcinoid of the lung

                        24. Pheochromocytoma, malignant

                        25. Paraganglioma

                        26. Carcinomas of pituitary gland, thyroid gland parathyroid gland and
                            adrenal cortex

                        27. Desmoid tumors

                        28. Peripheral nerve sheath tumors and NF1-related tumors

                        29. Malignant giant cell tumors

                        30. Chordoma

                        31. Adrenal cortical tumors

                        32. Tumor of unknown primary (Cancer of Unknown Primary; CuP)

                        33. Not Otherwise Categorized (NOC) Rare Tumors

                        34. Adenoid cystic carcinoma

                        35. Vulvar cancer

                        36. MetaPLASTIC carcinoma (of the breast)

                        37. Gastrointestinal stromal tumor (GIST)

                        38. Perivascular epithelioid cell tumor (PEComa)

                        39. Apocrine tumors/Extramammary Paget s Disease

                        40. Peritoneal mesothelioma

                        41. Basal cell carcinoma

                        42. Clear cell cervical cancer

                        43. Esthenioneuroblastoma

                        44. Endometrial carcinosarcoma (malignant mixed Mullerian tumors)

                        45. Clear cell endometrial cancer

                        46. Clear cell ovarian cancer

                        47. Gestational trophoblastic disease (GTD)

                        48. Gallbladder cancer

                        49. Small cell carcinoma of the ovary, hypercalcemic type

                        50. Angiosarcoma

                        51. High-grade neuroendocrine carcinoma

                        52. Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)

                        53. Anal cancer

                        54. Lymphoma

                        55. Merkel cell carcinoma

                        56. Pleural Mesothelioma

                        57. Sarcoma (bone & soft tissue)

                        58. Thymic Carcinoma

                        59. Uterine Leiomyosarcoma

                        60. Papillary RCC

        EXCLUSION CRITERIA:

          -  QTcF interval of >=450 msec at study entry; congenital long QT syndrome

          -  Sensory/motor neuropathy >= Grade 2

          -  Patients who are receiving any other investigational agents.

          -  Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS
             metastases are excluded, with the following exceptions:

               -  Patients with asymptomatic untreated CNS disease may be enrolled, provided all of
                  the following criteria are met:

                    -  Evaluable or measurable disease outside the CNS

                    -  No metastases to brain stem, midbrain, pons, medulla, or cerebellum

                    -  No history of intracranial hemorrhage or spinal cord hemorrhage

                    -  No ongoing requirement for dexamethasone for CNS disease; patients on a
                       stable dose of anticonvulsants are permitted.

                    -  No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1,
                       Day 1

               -  Patients with asymptomatic treated CNS metastases may be enrolled, provided all
                  the criteria listed above are met as well as the following:

                    -  Radiographic demonstration of improvement upon the completion of
                       CNS-directed therapy and no evidence of interim progression between the
                       completion of CNS-directed therapy and radiographic screening for the
                       current study

                    -  No stereotactic radiation or whole-brain radiation within 28 days prior to
                       Cycle 1, Day 1

                    -  Screening CNS radiographic study >=4 weeks from completion of radiotherapy
                       and >=2 weeks from discontinuation of corticosteroids

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to study drugs.

          -  Uncontrolled intercurrent illness including, but not limited to, serious untreated
             infection, symptomatic respiratory failure/congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements.

          -  Pregnant women are excluded from this study because nilotinib and paclitaxel have been
             assigned to pregnancy category D by the FDA. Because there is an unknown but potential
             risk for adverse events in nursing infants secondary to treatment of the mother with
             the study drugs, breastfeeding should be discontinued prior to the first dose of study
             drug and women should refrain from nursing throughout the treatment period and for 3
             months following the last dose of study drug.

          -  Patients who are known to be HIV-positive and on combination antiretroviral therapy
             are ineligible because of possible PK interactions with study drugs.
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response
Time Frame:12 months
Safety Issue:
Description:If at least 4/30 patients experience an objective response, defined as a complete or partial response by RECIST 1.1, the combination of nilotinib and paclitaxel will be considered promising. This design provides approximately 88% power to reject a null ORR of 0.05 when the true ORR is 0.2 (with one-sided type-I error of approximately 0.062).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Trial Keywords

  • Pharmacodynamic
  • Bcr-Abl Kinase Inhibitors
  • Taxanes
  • Combination

Last Updated

August 26, 2020